Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Thesis (MD (Anaesthesiology))--University of Pretoria, 2003. / Includes bibliographical references.

Hepatic ischaemia-reperfusion injury occurs when patients undergoing liver operations such as liver transplantation, tumour resection and shock. Intravenous and intrathecal administration of morphine can be used to provide analgesia prior or after liver surgery. It has been reported that systemically administered morphine conferred protective effect on numerous organs, including heart, brain and kidney. The focus of my research is to investigate the effect of intravenous and intrathecal morphine preconditioning on normal and cirrhotic livers. Further, PI3K/Akt, STAT3 and HO-1/iNOS pathways had been shown to ameliorate hepatic ischemia-reperfusion injury. Hence, we aim to investigate these possible signaling pathways associated with morphine mediated hepato-protection. A partial hepatic ischaemia reperfusion injury model in rats was used. The experiments were divided into two series: one involved in normal livers and the other one involved in cirrhotic livers. For the normal livers, morphine at different doses were administrated intravenously or intrathecally prior the onset of ischaemia, and the experiments were repeated with previous intravenous administration of naloxone methiodide (opioid receptor antagonist), or wortmannin (Akt inhibitor), respectively. For the cirrhotic livers, morphine at optimal doses were injected intravenously or intrathecally prior the onset of ischaemia. Those rats with only induced hepatic ischaemia-reperfusion injury only were marked as control groups. The effect of morphine preconditioning on hepatic architecture, apoptosis and liver function were evaluated respectively by hematoxylin-eosin (H&E) staining, Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) staining, the expression of cleaved Caspase-3, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the expression of phosphorylated Akt, phosphorylated JAK2, phosphorylated STAT3, HO-1 and iNOS were detected by Western Blot to determine the signaling pathways involved by intravenous and intrathecal morphine preconditioning. The normal livers series presented intravenous and intrathecal morphine preconditioning at the 100μg/kg, 10μg/kg, respectively, better persevered hepatic architecture when compared with control groups. The degree of liver cell apoptosis and expression of cleaved caspase-3 were also reduced by intravenous and intrathecal morphine preconditioning. In additional, intravenous and intrathecal morphine preconditioning ameliorated hepatocellular damage by reducing ALT&AST release. Moreover, the expressions of phosphorylated Akt and its downstream protein STAT3 were significantly increased by intravenous and intrathecal morphine preconditioning, compared with their respective control groups. The hepato-protective effect of intravenous and intrathecal morphine preconditioning was reversed by naloxone methiodide or wortmannin pretreatment. The similar pattern of protection was observed in cirrhotic livers. Both intravenous and intrathecal morphine preconditioning protected hepatic architecture much better than control groups. They also attenuated hepatic apoptosis degree and hepatocellular enzyme release. Furthermore, the expression of HO-1 was up-regulated, whereas the expression of iNOS was down-regulated by intravenous and intrathecal morphine preconditioning. In summary, this study provided evidence that intravenous and intrathecal morphine preconditioning could attenuate hepatic ischaemia-reperfusion injury in normal and cirrhotic livers. The involvement of opioid receptors, Akt/STAT3 pathway and HO-1 pathway might be the underlying mechanisms of morphine hepato-protection. Finally, the protective effect of morphine preconditioning might provide a potential therapeutic approach for clinical usage. / published_or_final_version / Anaesthesiology / Master / Master of Philosophy

Despite the advances made in our understanding of the molecular mechanistic actions of general anesthetics very little is known about the in vivo neural circuits involved in creating the state of general anesthesia. To date the common consensus is that general anesthetics act ubiquitously within the CNS. Recently, (Devor and Zalkind, 2001) have reported that microinjections of pentobarbital (PB) into a discrete brainstem focal area of conscious rats induced a classical, reversible general anesthesia-like behavioral state. The authors concluded that this area, termed the mesopontine tegmental anesthesia area (MPTA), may be important for the induction of general anesthesia. The purpose of the present project was to study the neurophysiological basis of the analgesia, which accompanied the state of general anesthesia induced by PB microinjections into the MPTA that was reported by (Devor and Zalkind, 2001). Here, sensory inflow via the spinothalamic tract (STT), a classical spinal nociceptive pathway in the rat, was assessed using single neuron extracellular recording techniques before, during and after microinjections of PB into the MPTA. Spontaneous firing rate (SFR), antidromic firing index (FI) and sciatic as well as sural nerve-evoked responses (Sc-, Su-ER) of STT neurons in isoflurane-anesthetized rats were quantified before as well as 2, 15, 30 and 60 min following bilateral microinjections of either PB (200 micrograms/side) or vehicle control solution (Vh, 1 microliter/side) into the MPTA. The group mean SFR, FI as well as magnitudes of Sc-, Su-ER of STT neurons were significantly and reversibly reduced following PB microinjections compared to corresponding baseline measurements. There were no significant changes in any of the three parameters following microinjections of Vh compared to the pre-microinjection baseline responses. The results from this study indicate that analgesia, which occurs during the anesthesia-like state following microinjections of PB into the MPTA, may be due to attenuation of sensory inflow through the STT. The suppression of STT neurons likely occurs via direct and/or indirect descending pathways from the MPTA to the spinal cord. This study provides the first direct electrophysiological evidence for the analgesia caused by PB microinjections into the rat MPTA.

Thesis (doctoral)--Lunds Universitet, 1990.

Thesis (doctoral)--Lunds Universitet, 1990.

Thesis (MSc.(Anatomy)--Faculty of Health Sciences)-University of Pretoria, 2004. / Summary in English and Afrikaans. Includes bibliographical references.

Orientadores: Maria Cristina Volpato, Eneida de Paula, Francisco Carlos Groppo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-15T12:59:46Z (GMT). No. of bitstreams: 1 Zago_PatriciaMariaWiziack1982-_M.pdf: 1548841 bytes, checksum: 532fa0a5d09fdd83740f529142e2e993 (MD5) Previous issue date: 2010 / Resumo: Estudos em animais têm demonstrado que a encapsulação lipossomal da prilocaína aumenta sua eficácia anestésica em tecidos moles. Este estudo randomizado, cruzado e cego teve por objetivo avaliar a eficácia anestésica da formulação lipossomal de prilocaína 3% comparada à prilocaína 3% sem aditivos e prilocaina 3% com felipressina 0,03UI/mL, aplicadas por técnica infiltrativa na região vestibular do canino superior direito em 32 voluntários. As formulações foram aplicadas em 3 sessões, com ordem aleatória de aplicação e intervalo mínimo de 1 semana. O sucesso, a latência e a duração da anestesia pulpar foram avaliados com aplicação de estímulo elétrico no incisivo lateral, canino e primeiro pré-molar superiores; a latência e duração da anestesia em tecidos moles foram avaliadas por pressão com instrumento rombo na gengiva inserida da região vestibular do canino superior direito e a dor à injeção por meio da escala analógica visual (EAV). Considerou-se como sucesso anestésico quando a latência foi menor ou igual a 10 minutos com duração mínima de 10 minutos. Os voluntários e o pesquisador que avaliou as anestesias não tinham conhecimento da formulação aplicada. Os resultados foram submetidos aos testes Kruskal-Wallis (latência e duração da anestesia pulpar), Tuckey (EAV), Friedman (duração da anestesia gengival), Log Rank e McNemar (sucesso). A formulação lipossomal apresentou resultados semelhantes à formulação sem aditivos (p>0,05) e estatisticamente inferiores à prilocaína com felipressina (p<0,05), com relação à duração de anestesia gengival e sucesso e duração de anestesia pulpar para o canino e pré-molar. Com relação a latência e sucesso da anestesia no incisivo lateral, a prilocaína lipossomal não diferiu das demais formulações (p>0,05) e a prilocaina sem aditivos apresentou menor sucesso e maior latência (p<0,05) que a prilocaína com felipressina. As formulações não diferiram quanto à duração de anestesia pulpar para o incisivo lateral, dor à injeção e latência anestésica para canino, pré-molar e gengiva (p>0,05). Conclui-se que a prilocaína lipossomal apresenta eficácia anestésica semelhante à solução sem aditivos e menor eficácia do que a solução de prilocaína com felipressina em infiltração na maxila, não havendo, portanto, vantagem no seu uso / Abstract: Animal studies have shown that liposome encapsulation increases prilocaine anesthetic efficacy in soft tissues. This randomized, blind, crossover, three period study evaluated the anesthetic efficacy of liposome-encapsulated 3% prilocaine compared to 3% plain prilocaine and 3% prilocaine with 0.03IU/mL felypressin, after 1.8mL infiltration in the buccal sulcus of the maxillary right canine, in 32 volunteers. The formulations were randomly applied in three sessions, spaced one week apart. Anesthesia success and onset and duration of pulpal anesthesia in the lateral incisor, canine and first premolar were evaluated by using an electric pulp tester; onset and duration of soft tissue anesthesia were evaluated by pinprick test in the buccal attached gingiva of maxillary right canine. Injection pain was analyzed through Visual Analogue Scale (VAS). Anesthesia was considered successful when the onset time was less than 10 minutes and the duration was at least 10 minutes. The volunteers and the researcher who evaluated anesthesia parameters were blind to the formulations injected. Results were submitted to Kruskal-Wallis (onset and duration of pulpal anesthesia), Tuckey (VAS), Friedman (duration of gingival anesthesia), Log-Rank and McNemar tests (anesthesia success), (?=5%). Liposomal prilocaine showed similar results in comparison to plain prilocaine (p>0.05), and lower anesthesia success and duration for canine and premolar and for duration of gingival anesthesia (p<0.05) than prilocaine with felypressin. Liposomal prilocaine did not differ from the other formulations concerning onset and anesthesia success for the lateral incisor (p>0.05); plain prilocaine presented lower success rate and slower onset of anesthesia for this tooth in comparison to prilocaine with felypressin (p<0.05). No differences were observed among the formulations in relation to duration of anesthesia for lateral incisor, VAS scores and onset of gingival and pulpal anesthesia for canine and premolar (p>0.05). In conclusion, liposomal prilocaine presents similar anesthetic efficacy in relation to plain prilocaine and lower efficacy in comparison to prilocaine with felypressin in maxillary infiltration. Therefore, there is no advantage in the use of this formulation / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestre em Odontologia

Despite the advances made in our understanding of the molecular mechanistic actions of general anesthetics very little is known about the in vivo neural circuits involved in creating the state of general anesthesia. To date the common consensus is that general anesthetics act ubiquitously within the CNS. Recently, (Devor and Zalkind, 2001) have reported that microinjections of pentobarbital (PB) into a discrete brainstem focal area of conscious rats induced a classical, reversible general anesthesia-like behavioral state. The authors concluded that this area, termed the mesopontine tegmental anesthesia area (MPTA), may be important for the induction of general anesthesia. The purpose of the present project was to study the neurophysiological basis of the analgesia, which accompanied the state of general anesthesia induced by PB microinjections into the MPTA that was reported by (Devor and Zalkind, 2001). Here, sensory inflow via the spinothalamic tract (STT), a classical spinal nociceptive pathway in the rat, was assessed using single neuron extracellular recording techniques before, during and after microinjections of PB into the MPTA. Spontaneous firing rate (SFR), antidromic firing index (FI) and sciatic as well as sural nerve-evoked responses (Sc-, Su-ER) of STT neurons in isoflurane-anesthetized rats were quantified before as well as 2, 15, 30 and 60 min following bilateral microinjections of either PB (200 micrograms/side) or vehicle control solution (Vh, 1 microliter/side) into the MPTA. The group mean SFR, FI as well as magnitudes of Sc-, Su-ER of STT neurons were significantly and reversibly reduced following PB microinjections compared to corresponding baseline measurements. There were no significant changes in any of the three parameters following microinjections of Vh compared to the pre-microinjection baseline responses. The results from this study indicate that analgesia, which occurs during the anesthesia-like state following microinjections of PB into the MPTA, may be due to attenuation of sensory inflow through the STT. The suppression of STT neurons likely occurs via direct and/or indirect descending pathways from the MPTA to the spinal cord. This study provides the first direct electrophysiological evidence for the analgesia caused by PB microinjections into the rat MPTA. / Pharmaceutical Sciences, Faculty of / Graduate

Att opereras under lokalanestesi innebär att patienten kan vara vaken under operationen, forskning visar på både positiva och negativa upplevelser av detta. Ångest och oro är påtagligt och att patienterna känner att de tappar kontrollen över situationen. Samtidigt är anestesisjuksköterskans roll viktig för att se och bekräfta patienten. Att låta patienten lyssna på musik kan vara ett verktyg som sjuksköterskan kan ta till, eftersom musik har kunnat minska ångest hos andra patientgrupper. Syftet med denna studie är att utforska upplevelser hos patienter som lyssnar på musik perioperativt i lokalanestesi. Den metod som används är en systematisk litteraturöversikt med en integrativ design. Resultatet baserades på 21 artiklar, varav 18 är kvantitativa och 3 kvalitativa. Studien utmynnar i fem teman; ångest, smärta, välbefinnande, coping och upplevelser utöver musiken. Musik påverkar patienternas ångest och smärta på olika sätt. Ofta lindras ångest och smärta men i flera studier har musiken ingen eller tveksam inverkan. Musiken har även effekter på patienternas välbefinnande och påverkar deras copingstrategi. Studien visar på viktiga upplevelser utöver musiken, där sjuksköterskans betydelse för patienten är framträdande. Musik visas öka patienternas välbefinnande men att sjuksköterskan har kännedom om hur smärtsamt och ångestladdat ett ingrepp är, kan vara angeläget för att inte lägga för stor tilltro till musikens effekt på patienten. Ytterligare forskning krävs för att få en ännu djupare förståelse och beskrivning av patienters upplevelse. Att även belysa olika ingrepps inverkan på patienternas upplevelse av musik, är av vikt.