Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical applications in PTSD

Post-traumatic stress disorder (PTSD) is a complex mental disorder that can develop in response to traumatic experiences. The molecular mechanisms underlying the pathology of PTSD are poorly understood, and this lack of knowledge hampers our ability to find superior therapeutic approaches to the treatment of this disorder. There are two main reasons for our lack of study in this area: here is no sufficiently validated animal model and lack of large-scale studies for the search of underlying molecular mechanisms. Thus, to promote research on PTSD (especially its molecular mechanisms) and to set molecular basis for searching novel medications of this disorder, large-scale, genome-wide interrogation of a significant amount of genes based upon a well validated animal model is demanded. We hypothesize that a significant number of genes are involved in PTSD. It is only with a large number of these genes identified in specific samples of PTSD-related population, and then it is possible for a sufficient understanding of the pathology at the molecular level of a PTSD, as well as for enhancing the PTSD's therapeutic and preventative strategies. Two prerequisites are needed for testing this hypothesis: (1) relative pure samples from a well validated animal model; and (2) genome-wide screening of PTSD molecular targets. For the animal model, we suggest to use the predator-exposure paradigm, in which rats are exposed to a predator, this model has previously been evaluated behaviorally well emulated the clinical symptoms of PTSD. For a better stringency, three criteria can be used to further validate this animal model: analogous (similarity of behavior), predictive (predictability of drug response) and biological mechanism (e.g., electrophysiological and pathological change in amygdala). For large-scale molecular target screening, the new microarray technology, which can profile expression of tens of thousands genes simultaneously, is the method of choice. The validity and practicability of this hypothesis and the strategy for its testing have been supported by our preliminary laboratory data.     

Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX−. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre–post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX− transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.     

Chemiluminescence: applications for the clinical laboratory

The chemical features and applications of chemiluminescence are reviewed, with special attention to bacterial and firefly bioluminescence and to uses of chemiluminescence in direct substrate assays, enzyme assays, solid-phase reactions, and immunoassays.     

Antinuclear antibodies: clinical applications

One of the common serological hallmarks of autoimmune disorders is the presence of various autoantibodies in the sera of patients affected by these disorders. Antinuclear antibodies (ANA) detection is often needed to aid the diagnosis in several autoimmune disorders. In view of the different methodologies available for their detection, it becomes essential to understand the advantages and pitfalls of each procedure. This brief review discusses some methodological aspects of ANA detection and the clinical relevance of the presence of some of the autoantibodies found in the sera of patients with autoimmune disorders.     

Cardiovascular ultrasound: applications for the assessment of cardiac function

Congestive heart failure(CHF) is usually associated with impaired left ventricular(LV) systolic function, and thus, the measurement of systolic function is an essential component of the evaluation of any patients with known or suspected cardiac disease. Among many parameters, most frequently used are LV percent fractional shortening and ejection fraction(EF), which can be easily measured from an M-mode echocardiogram. However, these M-mode measurements may be inaccurate in patients with asymmetrical LV due to myocardial infarction, right ventricular overload or sigmoid septum. Especially in such cases, EF should be measured using two-dimensional echocardiography. Usually, LV volumes and EF are calculated using the disc-summation method through the manual tracing of apical two-chamber and four-chamber echocardiograms. On the other hand, it has been recognized that congestive heart failure may arise in the absence of any systolic dysfunction and CHF due to systolic dysfunction never occurs in the absence of concomitant diastolic dysfunction. Although the analysis of pulsed-Doppler transmitral flow velocity has been most widely used for the noninvasive assessment of LV diastolic function, an increase in left atrial pressure during CHF can pseudonormalize an abnormal flow pattern and mask LV diastolic dysfunction. Recently, we proposed a new index for assessing LV diastolic function, flow propagation velocity, which can be measured with color M-mode Doppler echocardiography and baseline-shift technique. Recent studies have shown that the flow propagation velocity is a unique noninvasive parameter of LV diastolic function which can accurately detect the diastolic impairment in patients with different types of cardiac diseases with various loading conditions.     

Stress: A Psychophysiological Conception

Abstract

Physiological and psychological conceptions of stress have evolved independently within their respective fields. An attempt has been made to integrate the salient theoretical features of stress in a definition which accommodates them. The merits of this integration have been outlined. It is believed that the integrated approach will lead to interdisciplinary understanding among theoreticians, writers, and researchers and will allow a unified theoretical structure to grow.     

Tissue pH electrodes for clinical applications

The reduction of peripheral blood flow, which occurs during shock or in patients with occlusive arterial disease of the lower limb is accompanied by an increase in hydrogen ion activity in tissue cells. If this change could be measured, it could possibly be used as an indicator of tissue perfusion in such patients. Investigations have been carried out into various pH micro-electrode designs in order to construct one which could be used clinically to measure extracellular pH changes in skin. Experiments with antimony and externally insulated glass micro-electrodes demonstrated that these were unsatisfactory for the purpose. The successful design was insulated internally by means of a glass to glass fuse. It was robust, stable, sensitive and had a fast response time. Use of the electrode in normal volunteers produced reproducible skin pH values and demonstrated the feasibility of the system. Preliminary results using the micro-electrodes in patients indicate their possible application to the assessment of peripheral vascular disease, and to the monitoring of patients under intensive care.     

Advances in immunosensors for clinical applications

ABSTRACT

Immunoassay technique performs a fast, simple, reliable, and sensitive analysis of different compounds, being applied in several areas of interest such as clinical analysis for medical diagnosis, as well as in environmental analysis, and food quality control. The latest research activities in this field are represented by the attempts to achieve a low limit of detection by developing of new signal amplification strategies, eliminate the interferences, and decrease the cost of analysis.     

A comparison of MMPI and MMPI-2 in PTSD assessment

A sample of 47 Vietnam veterans with the diagnosis of combat-related Post-Traumatic Stress Disorder (PTSD) was administered the MMPI and MMPI-2. Pairwise comparisons were performed on the clinical scales, Harris Lingoes subscales, and scales relevant to the assessment of PTSD. Correlational analyses were performed as well. Hit rates of high-point pairs were compared across the tests. The results suggest a high degree of congruence between tests. Differences were seen on evaluations of some scales between tests that may influence interpretation and treatment.     

The assessment of posttraumatic stress disorder: With the clinician administered PTSD scale: Dutch results

The Clinician Administered PTSD Scale was employed with 76 traumatized Dutch subjects from different treatment centers and one social rehabilitation center. Subjects were traumatized either in childhood, in adolescence, or in early adulthood. The CAPS showed an overall agreement with clinical diagnosis of 79%, with a kappa coefficient of .58. Interrater agreement on the CAPS subscales of intensity (intrusion, avoidance, and hyperarousal) varied from .93 to .98. The internal consistency for all core symptoms of DSM-III-R at the CAPS intensity level for current PTSD was .89, and for lifetime PTSD .86. Concurrent validity was established by correlating the CAPS with the Mississippi Scale, the MMPI, and the Impact of Event Scale. All correlations were significant beyond .001. Finally, the CAPS items, both core symptoms and associative features, are discussed in detail at item level.     

Real-time PCR in clinical microbiology: applications for routine laboratory testing

Real-time PCR has revolutionized the way clinical microbiology laboratories diagnose many human microbial infections. This testing method combines PCR chemistry with fluorescent probe detection of amplified product in the same reaction vessel. In general, both PCR and amplified product detection are completed in an hour or less, which is considerably faster than conventional PCR detection methods. Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. The combination of excellent sensitivity and specificity, low contamination risk, and speed has made real-time PCR technology an appealing alternative to culture- or immunoassay-based testing methods for diagnosing many infectious diseases. This review focuses on the application of real-time PCR in the clinical microbiology laboratory.     

Macular pigment Raman detector for clinical applications

Clinical studies of carotenoid macular pigments (MP) have been limited by the lack of noninvasive, objective instruments. We introduce a novel noninvasive optical instrument, an MP Raman detector, for assessment of the carotenoid status of the human retina in vivo. The instrument uses resonant excitation of carotenoid molecules in the visible wavelength range, and quantitatively measures the highly specific Raman signals that originate from the single- and double-bond stretch vibrations of the pi-conjugated carotenoid molecule's carbon backbone. The instrument is a robust, compact device and suitable for routine measurements of MP concentrations in a clinical setting. We characterized and tested the instrument in clinical studies of human subjects to validate its function and to begin to establish its role as a possible screening test for macular pathologies. We also show that the MP Raman spectroscopy technology has potential as a novel, highly specific method for rapid screening of carotenoid antioxidant levels in large populations at risk for vision loss from age-related macular degeneration, the leading cause of blindness of the elderly in the developed world.     

An Application Language for Psychophysiological Experimentation

IBM 1130 (8K) Acronym: ABS (Adaptive Bio-Signal Language). Machine Sensible Materials: Preamplified biosignals. Documentation: Operating manual (80 pp. German). Author: F. Gerster. Submitted by: H. Legewie Submitter's Affiliation: Max-Planck-Institut für Psychiatric, Munich, Federal Republic of Germany ABS is an application language for biosignal processing and experimental control. It is running on an IBM 1130 which is connected to a WDV Lab Interface which allows biosignal input and process control output and which serves as a realtime clock. ABS is implemented on the basis of the IBM 1130/1800 macro assembler, so it can be adapted to an IBM 1800 with slight modifications. It allows the easy programming of individual ABS programs to solve a set of problems in psychophysiological experimentation: On-line acquisition and reduction of biosignals from up to 20 input channels, including 4 channels of EEG; simultaneous experimental control by simple statement for time scheduling, control of the output channels, logic and arithmetic operations applied to the reduced biosignals for feedback functions; facilities for on-line interaction with the experimenter and for on-line testing: organization of a complete data file of the experiment on a background storage device. Minimum Hardware: IBM 1130 (8K core and 520K disc), WDV Laboratory Interface¹ realtime clock, 8 analog, 8 digital, 4 trigger input channels; digital mag tape optional.