Application of Infrared Multiple Photon Dissociation (IRMPD) Spectroscopy in Chiral Analysis.

In recent years, methods based on photodissociation in the gas phase have become powerful means in the field of chiral analysis. Among them, infrared multiple photon dissociation (IRMPD) spectroscopy is a very attractive one, since it can provide valuable spectral and structural information of chiral complexes in addition to chiral discrimination. Experimentally, the method can be fulfilled by the isolation of target diastereomeric ions in an ion trap followed by the irradiation of a tunable IR laser. Chiral analysis is performed by comparing the difference existing in the spectra of enantiomers. Combined with theoretical calculations, their structures can be further understood on the molecular scale. By now, lots of chiral molecules, including amino acids and peptides, have been studied with the method combined with theoretical calculations. This review summarizes the relative experimental results obtained, and discusses the limitation and prospects of the method.

Emerging techniques in atherosclerosis imaging.

Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and "smart" contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque. This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology.

Infrared micro-spectroscopy of human tissue: principles and future promises.

This article summarizes the methods employed, and the progress achieved over the past two decades in applying vibrational (Raman and IR) micro-spectroscopy to problems of medical diagnostics and cellular biology. During this time, several research groups have verified the enormous information contained in vibrational spectra; in fact, information on protein, lipid and metabolic composition of cells and tissues can be deduced by decoding the observed vibrational spectra. This decoding process is aided by the availability of computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared micro-spectral data has enabled the collection of images of cells and tissues based solely on vibrational spectroscopic data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational spectroscopy in the biological and biomedical arenas.

Brain oxymetry in the operating room: current status and future directions with particular regard to cytochrome oxidase.

Near-infrared spectroscopy (NIRS) is a cerebral monitoring method that noninvasively and continuously measures cerebral hemoglobin oxygenation and the redox state of cytochrome oxidase using highly tissue-permeable near-infrared light. This technique now has wide clinical application, and its usefulness in the measurement of cerebral hemoglobin oxygenation has been confirmed under global cerebral injury and/or hypoxemic hypoxia; however, regional cerebral infarction located far from the monitoring site may not be detected by NIRS. Furthermore, the specificity and accuracy of the measurement of the redox state of cytochrome oxidase remain controversial. We apply NIRS to both animal and clinical investigations. Based on these results, we discuss the significance of the measurement of cerebral hemoglobin oxygenation and cytochrome oxidase in vivo and in clinical medicine. Using our algorithm, cytochrome oxidase signals are unaffected by hemoglobin signals, even when hematocrit values change from 35 to 5% under cardiopulmonary bypass in a dog model. In the clinical study, cytochrome oxidase during surgery is likely to be a good (though not perfect) predictor of postoperative cerebral outcome. NIRS appears to be a promising technology, but additional investigations are required to establish its clinical efficacy and justify its routine use during operative and perioperative periods.

Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives.

Quantum dots (QDs) are semiconductor nanocrystals that emit fluorescence on excitation with a light source. They have excellent optical properties, including high brightness, resistance to photobleaching and tunable wavelength. Recent developments in surface modification of QDs enable their potential application in cancer imaging. QDs with near-infrared emission could be applied to sentinel lymph-node mapping to aid biopsy and surgery. Conjugation of QDs with biomolecules, including peptides and antibodies, could be used to target tumors in vivo. In this review, we summarize recent progress in developing QDs for cancer diagnosis and treatment from a clinical standpoint and discuss future prospects of further improving QD technology to identify metastatic cancer cells, quantitatively measure the level of specific molecular targets and guide targeted cancer therapy by providing biodynamic markers for target inhibition.

Optical brain imaging in vivo: techniques and applications from animal to man.

Optical brain imaging has seen 30 years of intense development, and has grown into a rich and diverse field. In-vivo imaging using light provides unprecedented sensitivity to functional changes through intrinsic contrast, and is rapidly exploiting the growing availability of exogenous optical contrast agents. Light can be used to image microscopic structure and function in vivo in exposed animal brain, while also allowing noninvasive imaging of hemodynamics and metabolism in a clinical setting. This work presents an overview of the wide range of approaches currently being applied to in-vivo optical brain imaging, from animal to man. Techniques include multispectral optical imaging, voltage sensitive dye imaging and speckle-flow imaging of exposed cortex, in-vivo two-photon microscopy of the living brain, and the broad range of noninvasive topography and tomography approaches to near-infrared imaging of the human brain. The basic principles of each technique are described, followed by examples of current applications to cutting-edge neuroscience research. In summary, it is shown that optical brain imaging continues to grow and evolve, embracing new technologies and advancing to address ever more complex and important neuroscience questions.

Computing protein infrared spectroscopy with quantum chemistry.

Quantum chemistry is a field of science that has undergone unprecedented advances in the last 50 years. From the pioneering work of Boys in the 1950s, quantum chemistry has evolved from being regarded as a specialized and esoteric discipline to a widely used tool that underpins much of the current research in chemistry today. This achievement was recognized with the award of the 1998 Nobel Prize in Chemistry to John Pople and Walter Kohn. As the new millennium unfolds, quantum chemistry stands at the forefront of an exciting new era. Quantitative calculations on systems of the magnitude of proteins are becoming a realistic possibility, an achievement that would have been unimaginable to the early pioneers of quantum chemistry. In this article we will describe ongoing work towards this goal, focusing on the calculation of protein infrared amide bands directly with quantum chemical methods.

A perspective on medical infrared imaging.

Since the early days of thermography in the 1950s, image processing techniques, sensitivity of thermal sensors and spatial resolution have progressed greatly, holding out fresh promise for infrared (IR) imaging techniques. Applications in civil, industrial and healthcare fields are thus reaching a high level of technical performance. The relationship between body temperature and disease was documented since 400 bc. In many diseases there are variations in blood flow, and these in turn affect the skin temperature. IR imaging offers a useful and non-invasive approach to the diagnosis and treatment (as therapeutic aids) of many disorders, in particular in the areas of rheumatology, dermatology, orthopaedics and circulatory abnormalities. This paper reviews many usages (and hence the limitations) of thermography in biomedical fields.

Molecular and chemical characterization of blood cells by infrared spectroscopy: a new optical tool in hematology.

Infrared (IR) spectroscopy has made important contributions to the arena of hematology in the past decade. The normal physiology and pathologic modifications of the three cellular elements in blood, i.e., leukocytes, erythrocytes and platelets, have been thoroughly investigated by this recently emerged optical tool. By revealing subtle alterations in the structures of macromolecules in these blood cells, IR spectroscopy has become an ideal complementary analytical tool to conventional biochemical assays used to diagnose various common hematological disorders. Such traditional assays include molecular structure measurements that determine erythrocyte membrane fluidity and conformational changes, lipid profiling of platelet membranes, as well as assays of leukocyte proliferation and differentiation. IR spectroscopic-based techniques can be used to analyze DNA alterations, secondary structural changes in proteins, and to profile cellular lipids. From a molecular and biomedical perspective, IR spectroscopy has been explored for the diagnosis and prognosis of leukemia and beta-thalassemia, to predict drug sensitivity and resistance in chemotherapy patients, and more recently to examine apoptotic processes in blood cells. These studies have shown great promise in the early identification of drug-resistant patients and the early diagnosis of hematological disorders, especially malignancies. Furthermore, IR spectroscopic-based investigations will enable specific mechanisms underlying hematological disorders to be elucidated by revealing the molecular changes in the blood cells at a very early pathogenesis stage.

Recent advances in diffuse optical imaging.

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

Near infrared spectroscopy in brain injury: today's perspective.

The technique of near infrared spectroscopy (NIRS) is based on the principle of light attenuation by the chromophores oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and cytochrome oxidase. Changes in the detected light levels can therefore represent changes in concentrations of these chromophores. Clinical use of NIRS in the brain has been well established in neonates where transillumination is possible. While it has become a useful research tool for monitoring the adult brain, clinical application has been hampered by the fact that it must be applied in reflectance mode. This has resulted in a number of concerns, most significantly the issue of signal contamination by the extracranial tissue layers. Algorithms have been applied to try to overcome this problem, and techniques such as time resolved, phase resolved and spatially resolved spectroscopy have been developed. There has been renewed interest in NIRS as an easy to use, non-invasive technique for measuring tissue oxygenation in the adult brain. Recent technical advances have led to the development of compact, portable instruments that detect changes in optical attenuation of several wavelengths of light. Near infrared spectroscopy is an evolving technology that holds significant potential for technical advancement. In particular, NIRS shows future promise as a clinical tool for bedside cerebral blood flow measurements and as a cerebral imaging modality for mapping structure and function.

Tunable diode laser spectrometer for pulsed supersonic jets: application to weakly-bound complexes and clusters.

The design and operation of an apparatus for studying infrared spectra of weakly-bound complexes is described in detail. A pulsed supersonic jet expansion is probed using a tunable Pb-salt diode laser spectrometer operated in a rapid-scan mode. The jet may be fitted with either pinhole or slit shaped nozzles, the former giving lower effective rotational temperatures, and the latter giving sharper spectral lines. Notable features of the apparatus include use of a toroidal multi-pass mirror system to give over 100 passes of the laser through the supersonic jet, use of the normal laser controller for laser sweeping during both setup and data acquisition, and use of a simple semi-automated wavenumber calibration procedure. Performance of the apparatus is illustrated with observed spectra of the van der Waals complex He-OCS, and the seeded helium clusters He(N)-OCS and He(N)-CO.

Potential for detection of explosive and biological hazards with electronic terahertz systems.

The terahertz (THz) regime (0.1-10 THz) is rich with emerging possibilities in sensing, imaging and communications, with unique applications to screening for weapons, explosives and biohazards, imaging of concealed objects, water content and skin. Here we present initial surveys to evaluate the possibility of sensing plastic explosives and bacterial spores using field-deployable electronic THz techniques based on short-pulse generation and coherent detection using nonlinear transmission lines and diode sampling bridges. We also review the barriers and approaches to achieving greater sensing-at-a-distance (stand-off) capabilities for THz sensing systems. We have made several reflection measurements of metallic and non-metallic targets in our laboratory, and have observed high contrast relative to reflection from skin. In particular, we have taken small quantities of energetic materials such as plastic explosives and a variety of Bacillus spores, and measured them in transmission and in reflection using a broadband pulsed electronic THz reflectometer. The pattern of reflection versus frequency gives rise to signatures that are remarkably specific to the composition of the target, even though the target's morphology and position is varied. Although more work needs to be done to reduce the effects of standing waves through time-gating or attenuators, the possibility of mapping out this contrast for imaging and detection is very attractive.

Terahertz sources and detectors and their application to biological sensing.

Terahertz spectroscopy has long been used as an important measurement tool in fields such as radio astronomy, physical chemistry, atmospheric studies and plasma research. More recently terahertz technology has been used to develop an exciting new technique to investigate the properties of a wide range of biological materials. Although much research remains before a full understanding of the interaction between biomaterials and terahertz radiation is developed, these initial studies have created a compelling case for further scientific study. Also, the potential development of practical tools to detect and identify biological materials such as biological-warfare agents and food contaminants, or of medical diagnostic tools, is driving the need for improved terahertz technology. In particular, improved terahertz sources and detectors that can be used in practical spectroscopy systems are needed. This paper overviews some of the recent measurements of the terahertz spectra of biomaterials and the ongoing efforts to create an all-solid-state technology suitable not only for improved scientific experiments but also for military and commercial applications.

Litiasis renal inducida por indinavir / Indinavir and renal lithiasis

El indinavir es un nuevo, específico y potente fármaco que actúa, como otros agentes anti-retrovirales, inhibiendo la proteasa del virus de la inmunodeficiencia humana (VIH-1) o de la inmunodeficiencia adquirida (SIDA). El indinavir se une al centro activo del enzima, originando un descenso en plasma de ARN VIH-1 y un aumento de los linfocitos T-CD4 "helper" dando origen a un descenso del enzima, necesaria para la maduración y replicación del VIH-1.El presente trabajo estudia la cristaluria de dos de los nueve pacientes que padecían VIH-1 y/o SIDA tratados con indinavir, así como el cálculo formado por uno de los dos pacientes que presentaban cristaluria.El estudio se realizó con microscopio de luz polarizada y por espectrofotometría infrarroja, mostrando que la visualización de la cristaluria con microscopio de luz polarizada es útil para la caracterización de las mismas, así como para el estudio de los cálculos renales es útil el análisis por espectrofotometría infrarroja

Indinavir is a new specific and potent drug that inhibits, like other antiretroviral agents, the proteaseof immune deficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), an enzymenecessary to maduration and replication of the virus. Indinavir has the capacity to bind the activesite causing a decrease in plasma of HIV1-RNA and an increase of T-CD4 helper lymphocytes. Theaim of this work is to study in HIV and/or AIDS patients treated with indinavir the crystalluria andthe formation of renal calculi due to the clearance of this drug. Two out of nine patients studied inthis work presented abundant crystalluria and one of them presented spontaneously passed renalstone.Urinary crystals were studied under polarized-light microscopy and renal stone was analyzed byinfrared spectroscopy