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Dear Reader,

Welcome to the first of our regular newsletters. I hope the information you find here will augment your use of the Sarissa Biomedical product range by providing examples of other scientists' research using Sarissaprobes™. There will also be regular white papers and current literature reviews, and tips as to get the most out of your product.

Firstly, it's worth mentioning that we've had some staff-changes at Sarissa Biomedical over the last few months. At the end of March, Dr. Brian Stammers left us to focus on other business interests. Chris Buck stepped in to replace him and we also welcomed into the team our new Research and Development Technician, Mr. Jan Lopotar.

So, without further ado, I present Sarissa Biomedical's first newsletter. I hope you find this useful and welcome your feedback!

kind regards,

Prof. Nick Dale (Technical Director)
n.e.dale@sarissa-biomedical.com
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Whitepaper

"Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus"

Bruno G Frenguelli, Geoffrey Wigmore, Enrique Llaudet and Nicholas Dale
Journal of Neurochemistry, 2007

hippocampal slice
Figure 1. Hippocampal slice showing major cell regions (CA1, CA3) with stimulating (stim) and recording (rec) electrodes and sarissaprobes®-Ado, null and ATP.
In this study we addressed the chicken and egg of ischemic purine release: what is released into the extracellular space first by the brain when it is subjected to stroke-like conditions, ATP or adenosine? Sensible money might be on ATP - its full moniker, adenosine triphosphate, indicates that adenosine is a breakdown product of ATP - and so it is - but the question is: does this breakdown occur within or outside the cell?

Such an issue is not merely academic. ATP is a fast neurotransmitter and powerful modulator of central nervous system function that acts through at least 15 different G-protein coupled receptors and ligand-gated ion channels. Its release during brain ischemia can have weighty implications. Indeed, a great deal of evidence suggests that the activation of ATP receptors during stroke damages the brain. In contrast, adenosine is believed to protect the brain during such conditions. So, who you gonna call (first)? Yup, adenosine.

To definitively address this issue requires a means by which to simultaneously measure extracellular adenosine and ATP levels. Cue sarissaprobe®-ATP and sarissaprobe®-ADO. Insertion of these sensors into the hippocampal slice (Fig 1) allowed us to observe the release of adenosine practically immediately upon exposure of the slice to oxygen and glucose deficient medium (OGD). However, the release of ATP occurred much later, around the time of the anoxic depolarization, a widespread and profound depolarization of brain tissue that bodes ill for subsequent neuronal recovery.

Not only was there a temporal dissociation between the release of ATP and adenosine, but there were also mechanistic differences, most notably in the influence of extracellular calcium on purine release. Removing calcium facilitates adenosine release, but greatly reduces the release of ATP. These temporal and mechanistic differences allowed us to conclude that adenosine is release as such and rapidly upon OGD, whilst ATP only appears much later.

Such conclusions can only be arrived at through simultaneous and real time determination of extracellular transmitters and modulators. The sarissaprob® range of sensors not only allow this, but due to their miniature size, can be used in conjunction with optical or electrophysiological recordings (Fig 1) so that the release of neuroactive compounds can be correlated in real time with ongoing neuronal or glial cell activity. This powerful combination of techniques can only accelerate the study of intricate and overlapping cellular process. (Contributed by Bruno Frenguelli).
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News

  •   Sarissa Biomedical Founder Honoured

    Professor Nick Dale, Head of the Neurosciences Research Group in Biological Sciences, has been awarded a Milstein Award by the Medical Research Council for his innovative work into glucosensing (how the brain senses the level of glucose in the fluid that surrounds it).

    Nick dale, milstein award winner
    The Milstein Awards are new and very prestigious and sought-after – only ten are being awarded this year. The Medical Research Council (MRC) has created them to specifically encourage innovative research with high potential for scientific payback, but which may be too novel, involve too diverse a range of disciplines or be at too early a stage to fare well in the traditional peer-review process.

    Glucosensing: Effect on Metabolism.

    Nick’s project is important because glucosensing is a key part of "metabolic sensing" that controls things like food intake, fat storage etc. This is highly relevant to hot health issues such as the rising levels of obesity.

    Last year, with some collaborators at UCL, Nick demonstrated that the brain detects CO2 in blood via a mechanism that involves release of ATP (Adenosine Triphosphate). They were able to show this by using technology invented by Nick’s group at Warwick.

    Nick speculated that glucose sensing and CO2 sensing, both examples of "chemosensing", might involve shared common principles and that ATP could be important for the output signal from the glucosensing areas. His project is innovative in both its hypothesis and in its technological approach.

    This type of high-risk project would not be supported by conventional sources which require a lot of preliminary data. The Milstein Award is also an opportunity for Nick to bring his ideas to an area outside of his traditional area of expertise – which would also be unheard of in traditional funding streams.


  •   Sarissaprobe™ biosensors

    The sarissaprobe™ range remains focused on producing tools for investigating purinergic signaling. We offer biosensors for a range of purines: ATP, adenosine, inosine, hypoxanthine. However we have expanded our range to cover other transmitters. We currently sell acetylcholine biosensors and, given suitable demand, we can supply biosensors for glutamate and lactate. All our sensors are available in 0.5 and 2mm lengths. The shorter sensors are very suitable for use with brain slices, while the longer lengths of sensor can be better for in vivo recordings. Custom sensor sizes or shapes are possible.

    Future developments in the pipeline at Sarissa include production of a range of biosensors aimed at real-time measurement of gliotransmitter release.


  •   Screening and the selectivity of sarissaprobe™ biosensors

    Screened biosensors are now our standard product. We fabricate the biosensors with an inner screening layer, under the enzymatic biolayer, that rejects interferences on the basis of their size. This does not diminish the sensitivity or speed of the biosensor response to its analyte, but greatly reduces responses to electroactive compounds such as ascorbate, 5HT and dopamine. Screening also enhances the operational stability of the biosensors, as non-specific interferences can oxidize on the electrode surface and prevent it from detecting the H2O2 produced by the enzymatic reactions in the biolayer.

    We still recommend that you continue to use appropriate controls to check the specificity of your signal, but problems from interferences are greatly reduced. You should remember that the screen degrades with time and biosensor use, so we recommend testing the biosensors with an electroactive compound such as 5HT to check the integrity of the screen. It is possible to repair the screen (details are given on our Website), but we recommend that only experienced users attempt this.

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    Literature Review

    The Sarissa website maintains a bibliography of all papers published that use our biosensors. If you let us know when you publish a paper that uses the sarissaprobe™ biosensors and send us copy we shall include this in the bibliography and will give you a reduction on your next order of sarissaprobe™ biosensors. We also list here papers that have recently been published in the area of purinergic signaling which explore questions which the sarissaprobe™ biosensors may be useful in solving.

    • Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007), Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331-339.
    • Piet R, Jahr CE (2007) Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J Neurosci 27:4027-4035.
    • Todd KJ, Auld DS, Robitaille R (2007) Neurotrophins modulate neuron-glia interactions at a vertebrate synapse. Eur J Neurosci 25:1287-1296.
    • Striedinger K, Meda P, Scemes E (2007) Exocytosis of ATP from astrocyte progenitors modulates spontaneous Ca2+ oscillations and cell migration. Glia 55:652-662.
    • Martin ED, Fernandez M, Perea G, Pascual O, Haydon PG, Araque A, Cena V (2007) Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 55:36-45.
    • Bennett MR, Buljan V, Farnell L, Gibson WG (2006) Purinergic junctional transmission and propagation of calcium waves in spinal cord astrocyte networks. Biophys J 91:3560-3571.
    • Lin JH, Takano T, Arcuino G, Wang X, Hu F, Darzynkiewicz Z, Nunes M, Goldman SA, Nedergaard M (2007), Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev Biol 302:356-366.
    • Werry EL, Liu GJ, Bennett MR (2006) Glutamate-stimulated ATP release from spinal cord astrocytes is potentiated by substance P. J Neurochem 99:924-936.
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    About Sarissa Biomedical Ltd.

    The sarissaprobe™ range remains focused on producing tools for investigating purinergic signaling. We offer biosensors for a range of purines: ATP, adenosine, inosine, hypoxanthine. However we have expanded our range to cover other transmitters. We currently sell acetylcholine biosensors and, given suitable demand, we can supply biosensors for glutamate and lactate. All our sensors are available in 0.5 and 2mm lengths. The shorter sensors are very suitable for use with brain slices, while the longer lengths of sensor can be better for in vivo recordings. Custom sensor sizes or shapes are possible.

    Future developments in the pipeline at Sarissa include production of a range of biosensors aimed at real-time measurement of gliotransmitter release.

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    Disclaimer
    The material set out here is provided for information purposes only. Sarissa Biomedical does not take any responsibility for the accuracy of the information provided. Before making any investment decision, potential investors should consult their own professional advisors.

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