Comparison Evaluation of the Biological Effects of Sterigmatocystin and Aflatoxin B1 Utilizing SOS-Chromotest and a Novel Zebrafish (Danio rerio) Embryo Microinjection Method

Aflatoxin B1 (AFB1) is a potent mycotoxin and natural carcinogen. The primary producers of AFB1 are Aspergillus flavus and A. parasiticus. Sterigmatocystin (STC), another mycotoxin, shares its biosynthetic pathway with aflatoxins. While there are abundant data on the biological effects of AFB1, STC is not well characterised. According to published data, AFB1 is more harmful to biological systems than STC. It has been suggested that STC is about one-tenth as potent a mutagen as AFB1 as measured by the Ames test. In this research, the biological effects of S9 rat liver homogenate-activated and non-activated STC and AFB1 were compared using two different biomonitoring systems, SOS-Chromotest and a recently developed microinjection zebrafish embryo method. When comparing the treatments, activated STC caused the highest mortality and number of DNA strand breaks across all injected volumes. Based on the E. coli SOS-Chromotest, the two toxins exerted the same genotoxicities. Moreover, according to the newly developed zebrafish microinjection method, STC appeared more toxic than AFB1. The scarce information correlating AFB1 and STC toxicity suggests that AFB1 is a more potent genotoxin than STC. Our findings contradict this assumption and illustrate the need for more complex biomonitoring systems for mycotoxin risk assessment.     

Coordination of arm and eye movements in tracking of sinusoidally moving targets

Human subjects tracked sinusoidally moving visual targets with arm and eyes, in absence of visual feedback of the arm. The resulting frequency responses indicated that predictive mechanisms are involved both in arm and in eye tracking, and that the respective upper frequency limits are similar. Most importantly, substantial differences between arm and eye performance were observed: At low frequencies the gain of arm, but not of eye movement was consistently smaller than 0 dB. At higher frequencies arm, but not eye gain exhibited a marked amplitude non-linearity. The intra-trial gain and phase variability of arm movement was not correlated with the respective variability of eye movement. The reaction times to sudden changes of target parameters could be considerably different for arm and eye, and their inter-trial variability was not, or only marginally, correlated. Taken together, these findings strongly suggest that the mechanisms controlling predictive arm and eye movements in our experiment are organized to a major part in independent, parallel channels. The results are discussed with reference to a simple scheme of eye-arm coordination.     

Retrospective gating for mouse cardiac MRI.

Cardiac MR imaging in small animals presents some difficulties due to shorter cardiac cycles and smaller dimensions than in human beings, but prospectively gated techniques have been successfully applied. As with human imaging, there may be certain applications in animal imaging for which retrospective gating is preferable to prospective gating. For example, cardiac imaging in multiple mice simultaneously is one such application. In this work we investigate the use of retrospective gating for cardiac imaging in a mouse. Using a three-dimensional imaging protocol, we show that image quality with retrospective gating is comparable to prospectively gated imaging. We conclude that retrospective gating is applicable for small animal cardiac MRI and show how it can be applied to the problem of cardiac MRI in multiple mice.     

Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring.

Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFbeta) is involved in keloid formation. SMAD proteins play a crucial role in TGFbeta signaling and in terminating the TGFbeta signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFbeta signaling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars. Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFbeta1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis. Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (p<0.01) and normal skin fibroblasts (p<0.05). SMAD3 mRNA was found to be lower in keloids (p<0.01) and in normal scar fibroblasts (p<0.001) compared to normal skin fibroblasts. Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFbeta signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.     

Surface model of the gastrointestinal tract constructed from the Visible Korean

Most currently available three‐dimensional surface models of human anatomic structures have been artistically created to reflect the anatomy being portrayed. We have recently undertaken, as part of our Visible Korean studies, to build objective surface models based on cross‐sectional images of actual human anatomy. Objective of the present study was to elaborate surface models of the GI tract and neighboring structures that are helpful to medical simulation. The GI tract from stomach to anal canal was outlined and reconstructed from sectioned images of the Visible Korean (acomputer database containing the digitized transverse sectional images of a 33‐year‐old Korean man). The outlining procedure was supported by computational filtering and interpolation using commercially available software. The GI tract was divided into several parts, and each of these parts was surface reconstructed and then united with neighboring parts to produce a surface model of the complete GI tract. Surface models of about 100 neighboring structures were also prepared. The surface models produced will hopefully facilitate the development of interactive simulations for a variety of virtual abdominal surgical procedures or other educational programs. In addition, it is hoped that the improved outlining and surface reconstruction techniques described will encourage other researchers to construct similar surface models based on images obtained from different subjects. Clin. Anat. 22:601–609, 2009. © 2009 Wiley‐Liss, Inc.     

As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD) = −0.32, 95% CI −0.63 to −0.01, p = 0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry = 0.01, 95% CI −0.34 to 0.36, p = 0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.