*Monitoring of sterilizer function using biological indicators: experience from different out-patient clinics

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnHætta á dreifingu veirusýkinga með blóði í heilbrigðisþjónustu hefur leitt til þess að mælt er með reglulegu eftirliti á virkni dauðhreinsunarbúnaðar með notkun lífrænna vísa (sporaprófum). Tilgangur: Að kanna áreiðanleika dauðhreinsibúnaðar í klínískum aðstæðum utan sjúkrahúsa með notkun lífrænna vísa. Aðferðir: Könnunin náði til 184 heilbrigðisstofnana utan sjúkrahúsa á höfuðborgarsvæðinu, auk fjögurra húðflúrstofa. Um var að ræða aðgerðarstofur lækna, heilsugæslustöðvar og fótaaðgerðastofur. Við fyrsta próf leiddi sporaprófið í ljós að dauðhreinsun var ófullnægjandi í 70% hitaloftsofna og í 2.7% gufusæfa. Dauðhreinsun var sérstaklega ábótavant á fótaaðgerðastofum (76%). Betri árangur náðist eftir að starfsfólki hafði verið leiðbeint um dauðhreinsiaðferðir. Við endurtekningu stóðust 35% hitaloftsofnar ekki sporaprófið. Reglulegt eftirlit með dauðhreinsun utan sjúkrahúsa er gagnlegt við gæðaeftirlit. Nauðsynlegt er að setja reglur um að gæðaeftirlit með dauðhreinsibúnaði sé gert með líffræðilegum aðferðum.---------------------------------------------------------------------------------------------------------

Peripheral Regulation of Pain and Itch

Pain and itch are diverse sensory modalities, transmitted by the somatosensory nervous system. Stimuli such as heat, cold, mechanical pain and itch can be transmitted by different neuronal populations, which show considerable overlap with regards to sensory activation. Moreover, the immune and nervous systems can be involved in extensive crosstalk in the periphery when reacting to these stimuli. With recent advances in genetic engineering, we now have the possibility to study the contribution of distinct neuron types, neurotransmitters and other mediators in vivo by using gene knock-out mice. The neuropeptide calcitonin gene-related peptide (CGRP) and the ion channel transient receptor potential cation channel subfamily V member 1 (TRPV1) have both been implicated in pain and itch transmission. In Paper I, the Cre-LoxP system was used to specifically remove CGRPα from the primary afferent population that expresses TRPV1. CGRPα-mCherrylx/lx;Trpv1-Cre mice had attenuated responses to visceral pain induced by acid, while mechanosensitivity of the colon and somatic pain sensation remained unaffected. Mast cell proteases (MCPs) are stored in high quantities within mast cell (MC) granules and have been linked to both protective and pro-inflammatory properties, but little is known about their exact roles in vivo. In Papers II, IV and V, we used knock-out mice to investigate the contribution of MCs and their MCPs (the chymase mMCP4, tryptase mMCP6 and carboxypeptidase CPA3) in pain resulting from tissue injury, inflammation-induced heat hypersensitivity and different types of itch. Surprisingly, we found that neither MCPs nor MCs were essential for the pain behavior tested (Paper II). Our data indicate that mMCP6 and CPA3 have a protective role in scratching behavior induced by the peptide endothelin-1 (ET-1; Paper IV) and in scratching induced by the MC degranulator compound 48/80 (Paper V), but no differences were observed with the other pruritogens histamine, chloroquine or SLIGRL. In Paper III, we saw that a novel single-stranded oligonucleotide (ssON) attenuated compound 48-induced scratching in BALB/c mice by blocking MC degranulation. ssON could also block degranulation in human MC in vitro and we determined that this was due to ssON interfering with Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor involved in non-allergic MC degranulation. By better understanding the contribution of individual components of the nervous and immune systems in pain and itch, we hopefully increase the possibilities of developing better treatments for burdensome pain- and itch-related disorders in the future

Peripheral Regulation of Pain and Itch

Pain and itch are diverse sensory modalities, transmitted by the somatosensory nervous system. Stimuli such as heat, cold, mechanical pain and itch can be transmitted by different neuronal populations, which show considerable overlap with regards to sensory activation. Moreover, the immune and nervous systems can be involved in extensive crosstalk in the periphery when reacting to these stimuli. With recent advances in genetic engineering, we now have the possibility to study the contribution of distinct neuron types, neurotransmitters and other mediators in vivo by using gene knock-out mice. The neuropeptide calcitonin gene-related peptide (CGRP) and the ion channel transient receptor potential cation channel subfamily V member 1 (TRPV1) have both been implicated in pain and itch transmission. In Paper I, the Cre-LoxP system was used to specifically remove CGRPα from the primary afferent population that expresses TRPV1. CGRPα-mCherrylx/lx;Trpv1-Cre mice had attenuated responses to visceral pain induced by acid, while mechanosensitivity of the colon and somatic pain sensation remained unaffected. Mast cell proteases (MCPs) are stored in high quantities within mast cell (MC) granules and have been linked to both protective and pro-inflammatory properties, but little is known about their exact roles in vivo. In Papers II, IV and V, we used knock-out mice to investigate the contribution of MCs and their MCPs (the chymase mMCP4, tryptase mMCP6 and carboxypeptidase CPA3) in pain resulting from tissue injury, inflammation-induced heat hypersensitivity and different types of itch. Surprisingly, we found that neither MCPs nor MCs were essential for the pain behavior tested (Paper II). Our data indicate that mMCP6 and CPA3 have a protective role in scratching behavior induced by the peptide endothelin-1 (ET-1; Paper IV) and in scratching induced by the MC degranulator compound 48/80 (Paper V), but no differences were observed with the other pruritogens histamine, chloroquine or SLIGRL. In Paper III, we saw that a novel single-stranded oligonucleotide (ssON) attenuated compound 48-induced scratching in BALB/c mice by blocking MC degranulation. ssON could also block degranulation in human MC in vitro and we determined that this was due to ssON interfering with Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor involved in non-allergic MC degranulation. By better understanding the contribution of individual components of the nervous and immune systems in pain and itch, we hopefully increase the possibilities of developing better treatments for burdensome pain- and itch-related disorders in the future

Development of an assay of γ-amino butyric acid analogs in plasma, with special emphasis on pregabalin

Flogaveikilyfin vigabatrín, gabapentín og pregabalín eru byggingarlegar afleiður taugaboðefnisins γ-amínósmjörsýru (e. γ-amino butyric acid; GABA). Pregabalín er nýjast þessara lyfja, það var markaðssett árið 2004 sem Lyrica® hylki og auk þess að vera notað við flogaveiki hefur það ábendingar við taugaverkjum og kvíðaröskun. Misnotkun lyfsins er orðin þekkt vandamál þrátt fyrir að vímuáhrif þess séu hverfandi. γ-amínósmjörsýruafleiðurnar eru lítil og skautuð efni með litla ljósgleypni og því getur reynst örðugt að mæla þau. Mikilvægt er að geta mælt lyfin í blóði, bæði til að athuga meðferðarheldni flogaveikisjúklinga og, sérstaklega í tilfelli pregabalíns, í tilfellum þar sem um misnotkun er að ræða. Markmið þessa verkefnis var að þróa einfalda aðferð til að mæla þessi lyf í plasma, eftirsóknarvert væri að geta mælt þau öll samhliða en aðferðin var þó með það aðalmarkmið að mæla pregabalín, þar sem fáar mæliaðferðir fyrir það hafa verið birtar. Hér var farin sú leið að útbúa flúrljómandi afleiður af lyfjunum og mæla þau síðan með háþrýstivökvagreiningu og voru tvö mismunandi afleiðuefni prófuð: ortho-fþaldíaldehýð (OPA) og dansýl klóríð (Dns-Cl). Dns-Cl kom vel út og er þetta í fyrsta sinn svo vitað sé sem slík afleiða er útbúin af pregabalíni. Mæliaðferð fyrir pregabalín í plasma var gilduð samkvæmt viðurkenndum stöðlum ICH og síðan notuð til að mæla plasma- og blóðsýni sem borist höfðu Rannsóknastofu í lyfja- og eiturefnafræði með beiðni um slíka mælingu. Niðurstöður þeirra mælinga komu heim og saman við gögn sem birt hafa verið um blóðþéttni pregabalíns, bæði við eðlilega skammta og misnotkun. Því má álykta að nothæf mæliaðferð hafi verið þróuð

Þekking og viðhorf tengd verkjum og verkjameðferð : megindleg rannsókn meðal hjúkrunarfræðinga á Sjúkrahúsinu á Akureyri

Tilgangur rannsóknarinnar var að kanna þekkingu og viðhorf hjúkrunarfræðinga á Sjúkrahúsinu á Akureyri tengd verkjum og verkjameðferð. Við framkvæmd rannsóknarinnar var notuð megindleg rannsóknaraðferð þar sem upplýsinga var aflað með spurningalista. Notast var við spurningalistann Knowledge & Attitudes Survey Regarding Pain (K&A-SRP). Spurningalistinn var lagður fyrir alla hjúkrunarfræðinga sem voru við störf á Sjúkrahúsinu á Akureyri (n=177) á tímabilinu 28. janúar til 20. febrúar 2011, alls voru 64 hjúkrunarfræðingar sem svöruðu spurningalistanum en 62 spurningalistar voru nothæfir sem samsvarar 35% þátttöku. Við úrvinnslu gagna var notast við tölfræðiforritið Statistical Package for the Social Science (SPSS). Microsoft Office Excel og Microsoft Office Word voru einnig notuð við uppsetningu á súluritum og töflum. Niðurstöður rannsóknarinnar leiddu í ljós að þekking hjúkrunarfræðinga á Sjúkrahúsinu á Akureyri á verkjum og verkjameðferð virðist nokkuð góð og viðhorf vera nokkuð jákvæð þar sem þátttakendur svöruðu að meðaltali 25,4 spurningum rétt af 40 mögulegum eða 63,5%. Kannað var hvort munur væri á milli útkomu úr spurningalistanum og lýðfræðilegra breyta sem spurt var um, s.s. aldur, starfsaldur, starfsdeild o.fl.. Einungis var hægt að sýna fram á marktækan mun á milli starfsdeilda og útkomu úr spurningalistanum. Af niðurstöðum rannsóknarinnar telja rannsakendur einnig að hjúkrunarfræðingar á Sjúkrahúsinu á Akureyri standi nokkuð vel að vígi varðandi verki og verkjameðferð miðað við sambærilegar erlendar rannsóknir sem skoðaðar voru. Ósk rannsakenda er að niðurstöður rannsóknarinnar veki hjúkrunarfræðinga til umhugsunar og verði hvatning fyrir þá að íhuga hvar þeir standi gagnvart verkjum og verkjameðferð. Opna þarf umræðu um þetta mikilvæga málefni með það að markmiði að koma auga á það sem betur mætti fara í vinnubrögðum og skipulagi verkjameðferða. Lykilhugtök: verkir, þekking, viðhorf, verkjameðferð, hjúkrunarfræðingur

Padres y maestros

Incluye el suplemento: Cine y transversalesBiblioteca de Educación, Ministerio de Educación, Cultura y Deporte; C/ San Agustín 5; 28014 Madrid; Tel.+34917748000; [email protected]

*Monitoring of sterilizer function using biological indicators: experience from different out-patient clinics

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnHætta á dreifingu veirusýkinga með blóði í heilbrigðisþjónustu hefur leitt til þess að mælt er með reglulegu eftirliti á virkni dauðhreinsunarbúnaðar með notkun lífrænna vísa (sporaprófum). Tilgangur: Að kanna áreiðanleika dauðhreinsibúnaðar í klínískum aðstæðum utan sjúkrahúsa með notkun lífrænna vísa. Aðferðir: Könnunin náði til 184 heilbrigðisstofnana utan sjúkrahúsa á höfuðborgarsvæðinu, auk fjögurra húðflúrstofa. Um var að ræða aðgerðarstofur lækna, heilsugæslustöðvar og fótaaðgerðastofur. Við fyrsta próf leiddi sporaprófið í ljós að dauðhreinsun var ófullnægjandi í 70% hitaloftsofna og í 2.7% gufusæfa. Dauðhreinsun var sérstaklega ábótavant á fótaaðgerðastofum (76%). Betri árangur náðist eftir að starfsfólki hafði verið leiðbeint um dauðhreinsiaðferðir. Við endurtekningu stóðust 35% hitaloftsofnar ekki sporaprófið. Reglulegt eftirlit með dauðhreinsun utan sjúkrahúsa er gagnlegt við gæðaeftirlit. Nauðsynlegt er að setja reglur um að gæðaeftirlit með dauðhreinsibúnaði sé gert með líffræðilegum aðferðum.---------------------------------------------------------------------------------------------------------

Mouse mast cells and mast cell proteases do not play a significant role in acute tissue injury pain induced by formalin

Subcutaneous formalin injections are used as a model for tissue injury-induced pain where formalin induces pain and inflammation indirectly by crosslinking proteins and directly through activation of the transient receptor potential A1 receptor on primary afferents. Activation of primary afferents leads to both central and peripheral release of neurotransmitters. Mast cells are found in close proximity to peripheral sensory nerve endings and express receptors for neurotransmitters released by the primary afferents, contributing to the neuro/immune interface. Mast cell proteases are found in large quantities within mast cell granules and are released continuously in small amounts and upon mast cell activation. They have a wide repertoire of proposed substrates, including Substance P and calcitonin gene-related peptide, but knowledge of their in vivo function is limited. We evaluated the role of mouse mast cell proteases (mMCPs) in tissue injury pain responses induced by formalin, using transgenic mice lacking either mMCP4, mMCP6, or carboxypeptidase A3 (CPA3), or mast cells in their entirety. Further, we investigated the role of mast cells in heat hypersensitivity following a nerve growth factor injection. No statistical difference was observed between the respective mast cell protease knockout lines and wild-type controls in the formalin test. Mast cell deficiency did not have an effect on formalin-induced nociceptive responses nor nerve growth factor-induced heat hypersensitivity. Our data thus show that mMCP4, mMCP6, and CPA3 as well as mast cells as a whole, do not play a significant role in the pain responses associated with acute tissue injury and inflammation in the formalin test. Our data also indicate that mast cells are not essential to heat hypersensitivity induced by nerve growth factor

Amelioration of Compound 48/80-Mediated Itch and LL-37-Induced Inflammation by a Single-Stranded Oligonucleotide

Numerous inflammatory skin disorders display a high prevalence of itch. The Mas-related G protein coupled receptor X2 (MRGPRX2) has been shown to modulate itch by inducing non-IgE-mediated mast cell degranulation and the release of endogenous inducers of pruritus. Various substances collectively known as basic secretagogues, which include inflammatory peptides and certain drugs, can trigger MRGPRX2 and thereby induce pseudo-allergic reactions characterized by histamine and protease release as well as inflammation. Here, we investigated the capacity of an immunomodulatory single-stranded oligonucleotide (ssON) to modulate IgE-independent mast cell degranulation and, more specifically, its ability to inhibit the basic secretagogues compound 48/80 (C48/80)-and LL-37in vitroandin vivo. We examined the effect of ssON on MRGPRX2 activationin vitroby measuring degranulation in a human mast cell line (LAD2) and calcium influx in MRGPRX2-transfected HEK293 cells. To determine the effect of ssON on itch, we performed behavioral studies in established mouse models and collected skin biopsies for histological analysis. Additionally, with the use of a rosacea mouse model and RT-qPCR, we investigated the effect on ssON on LL-37-induced inflammation. We reveal that both mast cell degranulation and calcium influx in MRGPRX2 transfected HEK293 cells, induced by the antimicrobial peptide LL-37 and the basic secretagogue C48/80, are effectively inhibited by ssON in a dose-dependent manner. Further, ssON demonstrates a capability to inhibit LL-37 and C48/80 activationin vivoin two mouse models. We show that intradermal injection of ssON in mice is able to block itch induced via C48/80 in a dose-dependent manner. Histological staining revealed that ssON inhibits acute mast cell degranulation in murine skin treated with C48/80. Lastly, we show that ssON treatment ameliorates LL-37-induced inflammation in a rosacea mouse model. Since there is a need for new therapeutics targeting non-IgE-mediated activation of mast cells, ssON could be used as a prospective drug candidate to resolve itch and inflammation in certain dermatoses

Identification of a Neuronal Receptor Controlling Anaphylaxis

Allergic reactions can in severe cases induce a state of circulatory shock referred to as anaphylaxis. Histamine, the primary mediator of this condition, is released from immune cells, and, therefore, anaphylaxis has so far been considered an immune system disorder. However, we here show that the glutamatergic receptor mGluR7, expressed on a subpopulation of both peripheral and spinal cord neurons, controls histamine-induced communication through calcium-dependent autoinhibition with implications for anaphylaxis. Genetic ablation of mGluR7, and thus altered regulation of histamine-sensing neurons, caused an anaphylaxis-like state in mGluR7(-/-) mice, which could be reversed by antagonizing signaling between neurons and mast cells but not by antagonizing a central itch pathway. Our findings demonstrate the vital role of nervous system control by mGluR7 in anaphylaxis and open up possibilities for preventive strategies for this life-threatening condition