Dark-adapted red flash ERGs in healthy adults

Purpose: The x-wave of the dark-adapted (DA) ERG to a red flash reflects DA cone function. This exploratory study of healthy adults aimed to investigate changes in the DA red ERG with flash strength and during dark adaptation to optimise visualisation and therefore quantification of the x-wave. Methods: The effect of altering red flash strength was investigated in four subjects by recording ERGs after 20 minutes dark adaptation to red flashes (0.2–2.0 cd s m-2) using skin electrodes and natural pupils. The effect of dark adaptation duration was investigated in 16 subjects during 20 minutes in the dark, by recording DA 1.5 red ERGs at 1, 2, 3, 4, 5, 10, 15 and 20 minutes. Results: For a dark adaption period of 20 minutes, the x-wave was more clearly visualised to weaker (< 0.6 cd s m-2) red flash strengths: to stronger flashes it became obscured by the b-wave. For red flashes of 1.5 cd s m-2, the x-wave was most prominent in ERGs recorded after 1–5 minutes of dark adaptation: with longer dark-adaptation, it was subsumed into the b-wave’s rising edge. Conclusions: This small study suggests that x-wave visibility in healthy subjects after 20 minutes dark adaptation is improved by using flashes weaker than around 0.6 cd s m-2; for flash strengths of 1.5 cd s m-2, x-wave visibility is enhanced by recording after only around 5 minutes of dark adaptation. No evidence was found that interim red flash ERGs affecting the dark-adapted state of the normal retina

HGF-Induced PKCζ Activation Increases Functional CXCR4 Expression in Human Breast Cancer Cells

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading

GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons

Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABAB receptor-mediated responses at both synapse types. Postsynaptic GABAB receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (≥P30) suggesting developmental regulation. In young animals, the GABAB receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd2+, implicating presynaptic voltage-gated Ca2+ channels as a target for baclofen modulation. In contrast, although Cd2+ prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca2+ channels contributed equally to GABAB receptor-mediated inhibition of EPSCs, more P/Q-type Ca2+ channels were involved in GABAB receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABAB receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types

Assessment of visual disability using visual evoked potentials

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions.</p> <p>Methods</p> <p>A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9–42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19–36 years), 19 optic neuritis patients (19 eyes: ages 9–71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes.</p> <p>Results</p> <p>Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = −0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = −0.072x + 1.22 (−0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real disability in a range >5.77 μV. The results could be useful, especially in cases of no obvious pale disc with trauma.</p> <p>Conclusions</p> <p>Visual acuity quantification using absolute value of amplitude in pattern visual evoked potentials was useful in confirming subjective visual acuity for cutoff values >5.77 μV in disability evaluation to discriminate the malingering from real disability.</p