Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats

Breath ethane, O2 consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2 consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and PO2. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.     

Selective Antimicrobial Therapies for Periodontitis: Win the “Battle and the War”

Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the “battle” against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the “battle and the war”, new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.     

Microprogrammed computer simulator tools

A versatile microassembler and assembler program is described that was developed to facilitate the preparation of symbolic microprograms and assembly language programs for use with the microprogrammable computer simulator ET (educational tool) previously reported by the authors (see ibid., vol.E-30, p.135, Aug. 1987). The microassembler program takes as input a microprogram source file written in symbolic form and produces files ready for loading into the simulator's control ROM and address ROM. In addition, a file containing the mnemonics and corresponding op-codes of each instruction in the instruction set of the machine being simulated by the microprogram is created. The assembler program uses this file together with a user-written symbolic assembly language source program and produces a file containing machine language object code ready for loading into the simulator's RAM. Both the microassembler and the assembler also produce list files that may be examined by the user. Students of computer architecture indicate that use of these tools, in conjunction with the ET simulator, greatly simplifies the task of learning how microprogrammed computers function     

Tn and sialyl-Tn antigens,aberrant O-glycomics as human disease markers

In many different human disorders, the cellular glycome is altered. An interesting but poorly understood alteration occurs in the mucin-type O-glycome, in which there is aberrant expression of the truncated O-glycans Tn (GalNAcα1-Ser/Thr) and its sialylated version sialyl-Tn (STn) (Neu5Acα2,6GalNAcα1-Ser/Thr). Both Tn and STn are tumor-associated carbohydrate antigens and tumor biomarkers, since they are not expressed normally and appear early in tumorigenesis. Moreover, their expression is strongly associated with poor prognosis and tumor metastasis. The Tn and STn antigens are also expressed in other human diseases and disorders, such as Tn syndrome and IgA nephropathy. The major pathological mechanism for expression of the Tn and STn antigens is compromised T-synthase activity, resulting from alteration of the X-linked gene that encodes for Cosmc, a molecular chaperone specifically required for the correct folding of T-synthase to form active enzyme. This review will summarize our current understanding of the Tn and STn antigens in terms of their biochemistry and role in pathology.     

The role of quantitative ADME proteomics to support construction of physiologically based pharmacokinetic models for use in small molecule drug development

Pharmacokinetics (PK) refers to the time course of drug concentrations in the body and since knowledge of PK aids understanding of drug efficacy and safety, numerous PK studies are performed in animals and humans during the drug development process. In vitro to in vivo extrapolation and physiologically based pharmacokinetic (PBPK) modeling are tools that integrate data from various in silico, in vitro, and in vivo sources to deliver mechanistic quantitative simulations of in vivo PK. PBPK models are used to predict human PK and to evaluate the effects of intrinsic factors such as organ dysfunction, age, and genetics as well as extrinsic factors such as co-administered drugs. In recent years, the use of PBPK within the industry has greatly increased. However, insufficient data on how the abundance of metabolic enzymes and membrane transporters vary in different human patient populations and in different species has been a limitation. A major advance is therefore expected through reliable quantification of the abundance of these proteins in tissues. This review describes the role of PBPK modeling in drug discovery and development, outlines the assumptions involved in integrating protein abundance data, and describes the advances made and expected in determining abundance of relevant proteins through mass spectrometric techniques.     

A spatially augmented reality sketching interface for architectural daylighting design

We present an application of interactive global illumination and spatially augmented reality to architectural daylight modeling that allows designers to explore alternative designs and new technologies for improving the sustainability of their buildings. Images of a model in the real world, captured by a camera above the scene, are processed to construct a virtual 3D model. To achieve interactive rendering rates, we use a hybrid rendering technique, leveraging radiosity to simulate the interreflectance between diffuse patches and shadow volumes to generate per-pixel direct illumination. The rendered images are then projected on the real model by four calibrated projectors to help users study the daylighting illumination. The virtual heliodon is a physical design environment in which multiple designers, a designer and a client, or a teacher and students can gather to experience animated visualizations of the natural illumination within a proposed design by controlling the time of day, season, and climate. Furthermore, participants may interactively redesign the geometry and materials of the space by manipulating physical design elements and see the updated lighting simulation.     

Traffic signal light detection through sunglare filters of different Q factors

Recent guides for use of sunglare protection filters have introduced the concept of Q factors as a measure of colour appearance distortion in viewing traffic signal lights. The adoption of Q factor values was apparently arbitrary and not firmly based on experimental data. The manner in which changes in Q factor affect colour perception and detection of signal lights has been measured and shows that detection thresholds vary with the Q factor in a manner that can only partly be explained, but that is not independent of the colour of the signal as assumed in the guides. © 1997 John Wiley & Sons, Inc. Col Res Appl, 22, 24–31, 1997.     

Characterizing the MTF in 3D for a Quantized SPECT Camera Having Arbitrary Trajectories

The emergence of application-specific 3D tomographic small animal and dedicated breast imaging systems has stimulated the development of simple methods to quantify the spatial resolution or Modulation Transfer Function (MTF) of the system in three dimensions. Locally determined MTFs, obtained from line source measurements at specific locations, can characterize spatial variations in the system resolution and can help correct for such variations. In this study, a method is described to measure the MTF in 3D for a compact SPECT system that uses a 16 × 20 cm(2) CZT-based compact gamma camera and 3D positioning gantry capable of moving in different trajectories. Image data are acquired for a novel phantom consisting of three radioactivity-filled capillary tubes, positioned nearly orthogonally to each other. These images provide simultaneous measurements of the local MTF along three dimensions of the reconstructed imaged volume. The usefulness of this approach is shown by characterizing the MTF at different locations in the reconstructed imaged 3D volume using various (1) energy windows; (2) iterative reconstruction parameters including number of iterations, voxel size, and number of projection views; (3) simple and complex 3D orbital trajectories including simple vertical axis of rotation, simple tilt, complex circle-plus-arc, and complex sinusoids projected onto a hemisphere; and (4) object shapes in the camera's field of view. Results indicate that the method using the novel phantom can provide information on spatial resolution effects caused by system design, sampling, energy windows, reconstruction parameters, novel 3D orbital trajectories, and object shapes. Based on these measurements that are useful for dedicated tomographic breast imaging, it was shown that there were small variations in the MTF in 3D for various energy windows and reconstruction parameters. However, complex trajectories that uniformly sample the breast volume of interest were quantitatively shown to have slightly better spatial resolution performance than more simple orbits.     

Regression of subcutaneous lymphoma following removal of an ovarian granulosatheca cell tumor in a horse

A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous nodules and infertility. Fine-needle aspiration of one of the subcutaneous nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma. Palpation per rectum and transrectal ultrasonography revealed a mass associated with the left ovary. Excision of the ovarian tumor was performed, and a histopathologic diagnosis of granulosa-theca cell tumor was made. After removal of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring veterinarian reported that the nodules had also disappeared and then recurred after administration of a synthetic progestin. To further characterize the lymphoma and investigate this possible hormonal relationship, immunophenotyping and estrogen and progesterone receptor assays were performed. The subcutaneous lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen receptor assays were negative, and results of progesterone receptor assays were positive. Clinical observations of subcutaneous lymphoma in horses indicate that the waxing and waning nature of these tumors may be associated with the estrous cycle, pregnancy, foaling, and lactation. Clinical observations and identification of progesterone receptors suggest that a relationship between serum steroid hormone concentrations, such as estrogen and progesterone, and subcutaneous lymphoma may exists.