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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
191

The modulation of CD4⁺ T lymphocyte activity by adenosine A₂[A] receptor activation /

Lappas, Courtney Marcia. January 2006 (has links)
Thesis (Ph. D.)--University of Virginia, 2006. / Includes bibliographical references. Also available online through Digital Dissertations.
192

Effekte einer Glukose-Insulin-Kalium-Infusion auf den Anteil geretteten Myokards bei Patienten mit akutem Myokardinfarkt und Reperfusionstherapie ein randomisierter Vergleich /

Rosskopf, Andrea. January 2004 (has links) (PDF)
München, Techn. Univ., Diss., 2004.
193

Extrazelluläres ATP schützt vor dem akuten endothelialen Reperfusionsschaden

Kasseckert, Sascha Andreas. January 2006 (has links)
Universiẗat, Diss., 2006--Giessen.
194

Estudo da proteção renal durante a isquemia e reperfusão em ratos com o CAPE (caffeic acid phenethyl ester)

Roso, Nilson de Camargos [UNESP] 19 August 2011 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:30:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-19Bitstream added on 2014-06-13T19:19:21Z : No. of bitstreams: 1 roso_nc_dr_botfm.pdf: 1975320 bytes, checksum: 9363a3fa3f08654c7f41e33f7fc538a8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / o CAPE, ativo componente da própolis, é um potente antioxidante com importantes ações no estudo da isquemia e reperfusão renal. O objetivo deste estudo é avaliar o efeito do CAPE na lesão renal de isquemia-reperfusão em ratos anestesiados com isoflurano. Utilizou-se 26 ratos Wistar, machos, com peso superior a 250 g, distribuídos de modo aleatório em três grupos de animais, designados: G1 (controle, isquemia; n = 8); G2 (CAPE + isquemia; n = 10); G3 (diluente do CAPE (etanol) + isquemia; n = 8). Todos os grupos receberam indução da anestesia com isoflurano a 4% e a manutenção com isoflurano de 1,5 a 2,0%. A pressão arterial média (PAM) foi medida para controle da anestesia. A injeção intraperitoneal do CAPE (G2) ou do etanol (G3) foi feita 40 minutos antes da isquemia renal esquerda. Nos três grupos a isquemia durou 25 minutos. Todos os animais foram submetidos à nefrectomia direita. Os valores plasmáticos da creatinina foram determinados no início (M1), no final do experimento (M2) e 24 horas após o final do experimento (M3), quando os animais retornaram ao laboratório e foram anestesiados com isoflurano para coleta de amostra sanguínea e nefrectomia esquerda. Para análise histológica foi utilizada uma escala para avaliação da necrose tubular (0 a 5 = lesão máxima). Houve tratamento estatístico para os valores da temperatura dos animais, peso, PAM, da creatinina plasmática e das lesões histológicas, sendo as diferenças consideradas significantes quando p < 0,05. Conforme mediana, 1o e 3o quartis, entre colchetes, segundo o grupo, a creatinina foi maior em M2 do G2 (0,8 [0,6;0,8]) do que M2 do G1 (0,5[0,4;0,6]) e M2 do G3 (0,6[0,6;0,7]) com p = 0,0012. A creatinina também foi maior em M3 do G2 (3,7 [2,6;4,4]) do que M3 do G1 (0,9[0,7;1,4] e M3 do G3 (1,0[0,9;1,6] com p = 0,0014. Os valores... / CAPE, an active component of propolis, exhibits antioxidant properties with important actions on ischemia and reperfusion renal study. The purpose of this investigation was to examine the effect of CAPE in renal ischemia/reperfusion in rats anesthetized with isoflurane. Twenty six rats were randomly assigned in three groups: G1 (control, ischemia; n = 8); G2 (CAPE + ischemia; n = 10); G3 (dilute of CAPE (ethanol) + ischemia; n = 8). All groups were anesthetized with isoflurane. Mean arterial pressure (MAP) was monitored for anesthesia control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were realized 40 minutes before left renal ischemia. All animals underwent to right nephrectomy and left kidney was submitted to ischemia for 25 minutes. Serum creatinine values were determined in the beginning (M1) and at the end of experiment (M2) and 24 hours after the experiment (M3) rats were anesthetized with isoflurane and intracardiac blood sample was collected and the left kidney removed for histological analysis, using a scale for tubular necrosis (0-5= injury maximum). Statistical analysis was applied to the values of temperature, weight, MAP, serum creatinine and histological score injury and statistical differences were considered when p<0,05. There were no difference among the temperature of different groups. The weight of G2 were higher than others groups. The PAM of group G3 was higher in M2 than other groups. Creatinine values in M2 of group G2 were higher than M2 of group G1 and M2 of group G3 (p=0.0012) and were higher than M3 of group G1 and M3 of group G3 (p=0.0014). There was no difference of creatinine values in M1 of the three groups (p=0.054). Histological examination showed that group G2 had more acute tubular necrosis (2.0[2.0;3.0]) than group G1 (2.0[1.0;2.0]) and... (Complete abstract click electronic access below)
195

PHARMACOLOGICAL MODULATION OF SARCOPLASMIC RETICULUM CALCIUM ATPASE AND CALCIUM RELEASE CHANNELS FOR MUSCLE CELL PROTECTIVE ACTION

Lv, Yuanzhao 01 December 2015 (has links)
Abnormal homeostasis of intracellular Ca2+ plays a deleterious role in muscle pathologies by triggering processes that lead to dysfunction and necrotic or apoptotic cell death. One pathology where there is significant Ca2+ induced cell damage is ischemia, which initiates further damage (also mediated by Ca2+) generated by the required treatment process of revascularization; namely ischemia-reperfusion injury. Pharmacological agents used therapeutically for cell protection, especially for cardiac protection in ischemic heart diseases, have only directly targeted one of the elements regulating Ca2+ homeostasis, the L-type Ca2+ channels (calcium channel blockers). Other agents, like beta blockers, indirectly target various elements, including sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) and ryanodine receptors (RyRs). However, there are no pharmacological agents that directly and specifically target these two crucial elements required for intracellular SR Ca2+ homeostasis. Dr. Julio A. Copello’s group has previously studied the cardioprotective agent CGP-37157 (CGP), a benzothiazepine (BZT) derivative of the benzodiazepine (BZD) clonazepam. CGP was previously thought to decrease intracellular SR Ca2+ by acting as a blocker of the mitochondrial Na+/Ca2+ exchanger (Omelchenko et al., 2003). They found, however, that CGP also activates RyRs and inhibits the SERCA, which could better explain the SR effects of the drug (Neumann et al., 2011). These results suggest that drugs inducing partial depletion of SR Ca2+ stores could provide cellular protection in stressful circumstances or processes. The aims of the dissertation were organized based on the two processes that cause damage to muscle cells during ischemia: ischemia and subsequent reperfusion (ischemia-reperfusion injury) (Ibanez et al., 2015). Aim one and two focused on drug-protective action during the ischemic event, while aim three focused on drug protective action in the reperfusion (early post-ischemia) process. In the first Aim, experiments were designed to test the hypotheses that RyRs and/or SERCA could also be the target of i) Drugs with structural similarities to CGP (i.e., other BZTs and some BZDs) and ii) Drug known to confer cellular protection under stressful cellular conditions such as antiepileptic agents. We found that some BZTs (K201, CGP analog) and antiepileptic agents (Sipatrigine and Pimozide) demonstrated potential to prevent SR Ca2+ overload by inhibition of SERCA and, in some cases also by inducing mild activation of RyR channels. These results provided potential mechanisms of action for agents with cell protective action: targeting SERCA and preventing Ca2+ overload in pre-ischemia process. From the results of the first aim, K201 had the most significant effects in both SERCA inhibition and RyRs activation. Therefore, Aim 2 experiments focused on exploring with greater detail the action of the compound K201 on RyRs, SERCA and Ca2+ signaling. We found that K201 is a more potent SERCA blocker than RyR agonist and that SERCA inhibition remains under acidosis mimicking ischemic conditions. In Aim 3, the focus was on testing drugs with potential to prevent the overloaded SR from leaking Ca2+ (via RyRs) upon reperfusion. For that, we have examined various classes of organic polycationic agents in their ability to act as fast and reversible RyRs blockers. Currently, no agent with these characteristics is availableas a therapeutic or has been well defined for use as an experimental drug. The membrane permeable cation DHBP was identified as a potent RyR inhibitor with potential for rapid and transient inhibition of spontaneous SR Ca2+ release during reperfusion. In summary, we have defined the ability of some BZTs and antiepileptic agents (K201, CGP analog, Sipatrigine and Pimozide) to prevent/slow down SR Ca2+ overload by inhibition of SERCA, which may play an important role in their mechanisms of cell protection in ischemic events. In the case of BZT, these drugs may help their cause by producing mild activation of RyR2 channels, In addition, we have identify DHBP as a reversible and fast acting RyR inhibitor with potential as template for development of transient inhibitors of spontaneous SR Ca2+ release which may have significant protective action against injury during early reperfusion of the heart.
196

Obstrução experimental de jejuno em eqüinos: efeito da hidrocortisona nos parâmetros clínicos e laboratoriais

Costa, Nathalia dos Santos [UNESP] 22 January 2008 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-22Bitstream added on 2014-06-13T20:41:25Z : No. of bitstreams: 1 costa_ns_dr_jabo.pdf: 657826 bytes, checksum: ea3cd1fea9c1ec9dc87c6c0888f96d4d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A síndrome abdômen agudo é uma das principais doenças dos eqüinos, colocando em risco a vida do paciente quando não se institui rapidamente um tratamento adequado. Com o incremento de informações sobre lesões isquêmicas difundiu-se o conceito de que a reperfusão nestes tecidos, apesar de essencial para prevenir a morte celular por anoxia, induz efeito paradoxal de agravamento das lesões pré-existentes, o que se denomina lesão de reperfusão. Os glicocorticóides representam uma alternativa terapêutica para o tratamento das lesões de reperfusão. No estudo proposto foram utilizados 15 eqüinos adultos, machos e fêmeas, sem alterações clínicas aparentes, distribuídos aleatoriamente em três grupos de cinco animais, sob neuroleptoanalgesia e anestesia local, submetidos ou não à obstrução experimental do jejuno, mediante a colocação de um balão intraluminal, , para reproduzir a isquemia intestinal o quadro de abdômen agudo. Os eqüinos do grupo I foram submetidos a todas as manobras cirúrgicas aplicadas aos dos outros grupos, exceto a distensão do balão para provocar obstrução; os do grupo II foram submetidos à isquemia do jejuno durante 4 horas; e os grupo III foram submetidos à isquemia de 4 horas, seguida de tratamento com hidrocortisona uma hora antes da desobstrução. Para os exames laboratoriais, foram obtidas amostras de material biológico em quatro momentos: uma hora antes do procedimento cirúrgico e aplicação da neuroleptoanalgesia (M1), ao final da isquemia (M2) e uma hora (M3) e 18 horas (M4) após o início da reperfusão. Para a verificação de lesões à distância, as amostras de diversos órgãos foram colhidas na ocasião da necropsia ao término do experimento. / The acute abdomen syndrome is a common equine’s disease, which goes on risk the patient when a correct treatment is not established. The reperfusion in ischemical tissues, despite it is essential in preventing cell death by anoxia, leads a paradoxical effect in worsing the pre-existed lesions, was spread and its called reperfusion lesion. Glucocorticoids represents an alternative to treatment of reperfusion’s lesions. In the proposed study, were used 15 adults horses, male or female, without clinical apparent changes, distributed ramdonly in three groups of five animals. These animals were submitted or not to jejuni experimental obstruction through intraluminal ballon, under tranquilization and local anesthesia to imitate acute abdomen. The group I was submitted to surgical procedures, except the distention of the balloon to induce obstruction; the group II was submitted to jejuni’s ischemia for 4 hours and the group III was submitted to jejuni’s ischemia for 4 hours followed by hydrocortisone treatment one hour before desobstruction. For laboratorial tests, samples of biological material were obtained in four moments: one hour before surgical procedure and practice of drugs (M1), in the end of ischemia (M2) and one hour (M3) and 18 hours (M4) after the beginning of reperfusion. To verify distant lesions, samples of many organs were collected in the necropsy at the end of experiment.
197

Efeitos da pentoxifilina e da n-acetilcisteína em lesões causados por isquemia e reperfusão de órgão esplâncnicos em ratos

Cerqueira, Nereide Freire [UNESP] January 2003 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:27:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2003Bitstream added on 2014-06-13T18:31:10Z : No. of bitstreams: 1 cerqueira_bf_dr_botfmvz.pdf: 1499209 bytes, checksum: 7ff8a218fa7c9053994488fe2ecdb205 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A oclusão e a reperfusão das artérias esplâncnicas provoca alterações locais e sistêmicas derivadas principalmente da liberação de substâncias citotóxicas e da interação entre neutrófilos e células endoteliais. Buscando-se estudar os efeitos da pentoxifilina e da n-acetilcisteína em lesões provocadas em um modelo de isquemia e reperfusão (I/R), 60 ratos foram divididos em 6 grupos: SAL/CONT (salina/controle): animais submetidos à cirurgia, mas não à I/R, tratados com solução fisiológica; SAL/ISQ (salina/isquemia): animais submetidos à oclusão da artéria celíaca (AC), artéria mesentérica cranial (AMCr) e artéria mesentérica caudal (AMCa) durante 30 minutos, seguidos de 120 minutos de reperfusão, tratados com solução fisiológica; PTX/CONT: animais submetidos à cirurgia, mas não à I/R, tratados com pentoxifilina; PTX/ISQ: animais submetidos à I/R, tratados com pentoxifilina; NAC/CONT: animais submetidos à cirurgia, mas não à I/R, tratados com n-acetilcisteína; NAC/ISQ: animais submetidos à I/R, tratados com n-acetilcisteína. Os parâmetros avaliados foram pressão arterial média (PAM) carótida, pressão venosa jugular, fluxo sangüíneo na aorta e na AMCr, temperatura esofágica, hematócrito, hemogasometria, histologia intestinal, dosagem de espécies reativas ao ácido tiobarbitúrico (TBARS) em duodeno, jejuno e íleo e de malondialdeído (MDA) plasmático e do íleo. Nos grupos submetidos à I/R, a PAM teve queda significativa após 120 minutos de reperfusão; a pressão venosa não mostrou alterações no decorrer do experimento; houve queda do fluxo sangüíneo na aorta após os 30 minutos de isquemia, com queda mais acentuada ao final do período de reperfusão; o fluxo sangüíneo na AMCr diminuiu significativamente após 120 minutos de reperfusão, porém, em menor grau no grupo NAC/ISQ; a freqüência... . / Splanchnic artery occlusion and reperfusion result in local and remote tissue destruction caused by toxic factors released into the circulation and by neutrophil-endothelial cell interactions. In order to evaluate the effects of pentoxifylline (PTX) and n-acetilcysteine (NAC) on ischemia/reperfusion model (I/R), sixty rats were allocated into six groups: 1) SAL/CONT: Sham operation + saline; 2) SALI/ISQ: 30 min celiac, cranial and caudal mesenteric arteries occlusion + 120 min reperfusion + saline; 3) PTX/CONT: Sham operation + PTX (50 mg/kg); 4) PTX/ISQ: I/R + PTX; 5) NAC/SAL: Sham operation + NAC (430 mg/kg) and 6) NAC/ISQ: I/R + NAC. In all groups above mean arterial blood pressure (MABP), vein pressure, aorta and cranial mesenteric artery blood flow, heart rate, esophagus temperature, hematocrit, blood gas determination, histology, thiobarbituric acid reaction species (TBARS) and malondialdehyde (MDA) levels were determined. In I/R groups, MABP decreased significantly 120 minutes after reperfusion (p<0,05); as no difference in vein pressure were observed. Aorta blood flow decreased 30 minutes after ischemia, decreasing dramatically following restoration of blood flow. Cranial mesenteric artery blood flow decreased significantly after reperfusion, although the fall in NAC/ISQ group was attenuated. During the assays, heart rate was reduced, temperature decreased progressively and metabolic acidosis took place. Pentoxiffyline prevented histopathologic signs of injury in duodenum, jejunum and ileum, as well as n-acetilcysteine prevented ileum histopathologic signs of injury. I/R caused TBARS increase in NAC group jejunum and saline group ileum, but no difference was observed in plasmatic and ileal MDA. The present study allowed concluding that PTX was more efficient in preventing histophatologic injury than NAC, but neither PTX nor NAC... (Complete abstract, click electronic address below).
198

Estudo da proteção renal durante a isquemia e reperfusão em ratos com o CAPE (caffeic acid phenethyl ester) /

Roso, Nilson de Camargos. January 2011 (has links)
Orientador: Pedro Thadeu Galvão Vianna / Banca: Luiz Antonio Vane / Banca: João Abrão / Banca: Antonio Carlos Aguiar Brandão / Banca: Flora Margarida Barra Bisinotto / Resumo: o CAPE, ativo componente da própolis, é um potente antioxidante com importantes ações no estudo da isquemia e reperfusão renal. O objetivo deste estudo é avaliar o efeito do CAPE na lesão renal de isquemia-reperfusão em ratos anestesiados com isoflurano. Utilizou-se 26 ratos Wistar, machos, com peso superior a 250 g, distribuídos de modo aleatório em três grupos de animais, designados: G1 (controle, isquemia; n = 8); G2 (CAPE + isquemia; n = 10); G3 (diluente do CAPE (etanol) + isquemia; n = 8). Todos os grupos receberam indução da anestesia com isoflurano a 4% e a manutenção com isoflurano de 1,5 a 2,0%. A pressão arterial média (PAM) foi medida para controle da anestesia. A injeção intraperitoneal do CAPE (G2) ou do etanol (G3) foi feita 40 minutos antes da isquemia renal esquerda. Nos três grupos a isquemia durou 25 minutos. Todos os animais foram submetidos à nefrectomia direita. Os valores plasmáticos da creatinina foram determinados no início (M1), no final do experimento (M2) e 24 horas após o final do experimento (M3), quando os animais retornaram ao laboratório e foram anestesiados com isoflurano para coleta de amostra sanguínea e nefrectomia esquerda. Para análise histológica foi utilizada uma escala para avaliação da necrose tubular (0 a 5 = lesão máxima). Houve tratamento estatístico para os valores da temperatura dos animais, peso, PAM, da creatinina plasmática e das lesões histológicas, sendo as diferenças consideradas significantes quando p < 0,05. Conforme mediana, 1o e 3o quartis, entre colchetes, segundo o grupo, a creatinina foi maior em M2 do G2 (0,8 [0,6;0,8]) do que M2 do G1 (0,5[0,4;0,6]) e M2 do G3 (0,6[0,6;0,7]) com p = 0,0012. A creatinina também foi maior em M3 do G2 (3,7 [2,6;4,4]) do que M3 do G1 (0,9[0,7;1,4] e M3 do G3 (1,0[0,9;1,6] com p = 0,0014. Os valores... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: CAPE, an active component of propolis, exhibits antioxidant properties with important actions on ischemia and reperfusion renal study. The purpose of this investigation was to examine the effect of CAPE in renal ischemia/reperfusion in rats anesthetized with isoflurane. Twenty six rats were randomly assigned in three groups: G1 (control, ischemia; n = 8); G2 (CAPE + ischemia; n = 10); G3 (dilute of CAPE (ethanol) + ischemia; n = 8). All groups were anesthetized with isoflurane. Mean arterial pressure (MAP) was monitored for anesthesia control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were realized 40 minutes before left renal ischemia. All animals underwent to right nephrectomy and left kidney was submitted to ischemia for 25 minutes. Serum creatinine values were determined in the beginning (M1) and at the end of experiment (M2) and 24 hours after the experiment (M3) rats were anesthetized with isoflurane and intracardiac blood sample was collected and the left kidney removed for histological analysis, using a scale for tubular necrosis (0-5= injury maximum). Statistical analysis was applied to the values of temperature, weight, MAP, serum creatinine and histological score injury and statistical differences were considered when p<0,05. There were no difference among the temperature of different groups. The weight of G2 were higher than others groups. The PAM of group G3 was higher in M2 than other groups. Creatinine values in M2 of group G2 were higher than M2 of group G1 and M2 of group G3 (p=0.0012) and were higher than M3 of group G1 and M3 of group G3 (p=0.0014). There was no difference of creatinine values in M1 of the three groups (p=0.054). Histological examination showed that group G2 had more acute tubular necrosis (2.0[2.0;3.0]) than group G1 (2.0[1.0;2.0]) and... (Complete abstract click electronic access below) / Doutor
199

PrÃ-condicionamento nutricional com misturas de Ãleos Ãmega-3, 6 e 9 na isquemia e reperfusÃo cerebral em ratos / Preconditioning with Omega-3, 6 and 9 fatty acids mixes in brain ischemia and reperfusion in rats

Petrucia Antero Pinheiro 30 September 2011 (has links)
CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Os Ãcidos graxos insaturados Ãmega-3 (&#969;-3) e Ãmega-9 (&#969;-9) possuem aÃÃo anti-inflamatÃria e antioxidante, enquanto os Ãmega-6 (&#969;-6) sÃo prÃ-inflamatÃrios. Este estudo verificou os efeitos do prÃ-condicionamento com misturas de Ãleos contendo baixa relaÃÃo &#969;-6/&#969;-3 e elevada relaÃÃo &#969;-9/&#969;-6, em modelo experimental de isquemia-reperfusÃo cerebral. Foram utilizados 42 ratos Wistar, divididos em dois grupos: Controle (n=24) e Teste (n=18). O grupo Controle foi subdividido em 4 grupos de 6 animais, cada: Simulado - Ãgua (Sim-Ãgua), Isquemia-ReperfusÃo - Ãgua (IR-Ãgua), Simulado - IsolipÃdico (Sim-IsolipÃdico) e Isquemia-ReperfusÃo - IsolipÃdico (IR-IsolipÃdico). Os animais receberam Ãgua ou uma mistura isolipÃdica com relaÃÃes &#969;-6/&#969;-3 = 8:1 e &#969;-9/&#969;-6 = 0,4:1 por via orogÃstrica, durante sete dias, conforme seus grupos. O grupo Teste foi subdividido em 3 grupos de 6 animais: IR-Mix1, IR-Mix2 e IR-Mix3. Os animais do grupo Teste receberam misturas oleosas com relaÃÃes &#969;-6/&#969;-3 = 1,4:1 e &#969;-9/&#969;-6 = 3,4:1 , diferindo apenas na fonte de &#969;-3: Mix1, contendo o Ãcido &#969;-3 &#945;-linolÃnico; Mix2, contendo os Ãcidos &#969;-3 &#945;-linolÃnico, eicosapentaenÃico e docosaexaenoico, e Mix 3, contendo os Ãcidos &#969;-3 &#945;-linolÃnico e docosaexaenÃico, administradas por via orogÃstrica, durante sete dias. No sÃtimo dia, os animais dos grupos IR-Ãgua, IR-IsolipÃdico, IR-Mix1, IR-Mix2 e IR-Mix3 foram submetidos à isquemia cerebral com oclusÃo bilateral das artÃrias carÃtidas comuns por 1 hora, seguida de reperfusÃo por 3 horas. Os animais dos grupos Sim-Ãgua e Sim-IsolipÃdico foram submetidos à operaÃÃo simulada. Ao final do experimento, todos os animais foram decapitados e seus cÃrebros fatiados para anÃlise histopatolÃgica da Ãrea CA3 do hipocampo. A morte neuronal foi quantificada pela contagem de neurÃnios vermelhos (NV). Constatou-se que a quantidade de NV no grupo IR-Ãgua (36,83  9,79) foi maior (P = 0,0046) que a observada do grupo Sim-Ãgua (17,67  8,48), bem como a quantidade de NV no grupo IR-IsolipÃdico (29,83  12,19) foi maior (P = 0,0459) que a observada no grupo Sim-IsolipÃdico (14,17  11,62). NÃo foi constatada diferenÃa na quantidade de NV entre os grupos Sim-Ãgua (17,67  8,48) e Sim-IsolipÃdico (14,17  11,62), ou entre os grupos IR-Ãgua (36,83  9,79) e IR-IsolipÃdico (29,83  12,19). A quantidade de NV no grupo IR-Mix1 (12,33  6,31) foi menor que a verificada nos grupos IR-Ãgua (36,83  9,79; P < 0,01) e IR-IsolipÃdico (29,83  12,19; P < 0,05). As quantidades de NV nos grupos IR-Mix2 (10,67  2,81) e IR-Mix3 (7,33  6,47) tambÃm foram menores que as verificadas nos grupos IR-Ãgua (36,83  9,79; P < 0,001) e IR-IsolipÃdico (29,83  12,19; P < 0,01). NÃo foram constatadas diferenÃas nas quantidades de NV entre os grupos IR-Mix1 (12,33  6,31), IR-Mix2 (10,67  2,81) e IR-Mix3 (7,33  6,47), entre si. Conclui-se que, independentemente da fonte de &#969;-3, o prÃ-condicionamento com misturas de Ãleos contendo baixa relaÃÃo &#969;-6/&#969;-3 e elevada relaÃÃo &#969;-9/&#969;-6, protege os neurÃnios contra as lesÃes de isquemia-reperfusÃo cerebral em modelo experimental. / Omega-3 (&#969;-3) and omega-9 (&#969;-9) unsaturated fatty acids are anti-inflammatory and antioxidant, while omega-6 (&#969;-6) fatty acids are pro-inflammatory. This study investigated the preconditioning effects of fatty acids mixes with low ratio &#969;-6/&#969;-3 and high ratio &#969;-9/&#969;-6, in a brain ischemia-reperfusion experimental model. Forty-two Wistar rats were aleatory assigned to two groups: Control (n=24) and Test (n=18). Control group was divided into 4 groups, each with 6 animals: Water-Simulated (Water-Sim), Water - Ischemia-Reperfusion (Water-IR), Isolipid-Simulated (Isolipid-Sim) and Isolipid - Ischemia-Reperfusion (Isolipid-IR). The animals received water or a isolipid mix with &#969;-6/&#969;-3 ratio of 8:1 and &#969;-9/&#969;-6 ratio of 0,4:1 by gavage, for 7 days, according to their groups. Test group was divided into 3 groups of 6 animals: Mix1-IR, Mix2-IR, and Mix3-IR. All animals from Test group received oil mixes with &#969;-6/&#969;-3 ratio of 1,4:1 and &#969;-9/&#969;-6 ratio of 3,4:1 , differing only on the &#969;-3 source: Mix1, with &#969;-3 linolenic acid; Mix2, with &#969;-3 linolenic, eicosapentaenoic and docosahexaenoic acids, and Mix 3, with &#969;-3 linolenic and docosahexaenoic acids, by gavage, for 7 days. At the 7th day, animals from Water-IR, Isolipid-IR, Mix1-IR, Mix2-IR, and Mix3-IR groups were subjected to 1-hour brain ischemia by occlusion of both common carotid arteries, followed by a 3-hour reperfusion. Animals from Water-Sim and Isolipid-Sim groups were submitted to a simulated operation. At the end of the experiment, all animals were decapitated and their brains were sliced and sent to histological analysis of the CA3 hippocampal region. Neuronal death was quantified by the red neurons (RN) count. It was found that the number of RN in Water-IR group (36.83  9.79) was higher (P = 0.0046) than the number observed in Water-Sim group (17.67  8.48), and similarly, the number of RN in Isolipid-IR group (29.83  12.19) was higher (P = 0.0459) than the number observed in Isolipid-Sim group (14.17  11.62). There was no difference between the amount of RN from Water-Sim (17.67  8.48) and Isolipid-Sim (14.17  11.62) groups, nor between Water-IR (36.83  9.79) and Isolipid-IR (29.83  12.19) groups. The number of RN in Mix1-IR group (12.33  6.31) was lower than the number seen in Water-IR (36.83  9.79; P < 0.01) and Isolipid-IR (29.83  12.19; P < 0.05) groups. The amounts of RN in Mix2-IR (10.67  2.81) and Mix3-IR (7.33  6.47) groups were also lower than the amounts observed in IR-Water (36.83  9.79; P < 0.001) and IR-Isolipid (29.83  12.19; P < 0.01) groups. There were no differences between the Mix1-IR (12.33  6.31), Mix2-IR (10.67  2.81) and Mix3-IR (7.33  6.47) groups. In conclusion, regardless of the source of &#969;-3, preconditioning with fatty acids mixes with low ratio &#969;-6/&#969;-3 and high ratio &#969;-9/&#969;-6, protects the neurons against brain ischemia-reperfusion injuries in this experimental model.
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Isquemia-reperfusão hepática em ratos: efeitos da administração endovenosa da solução salina hipertônica a 7,5% associada a pentoxifilina / Liver ischemia-reperfusion in rats: the synergistic effects of hypertonic saline solution and pentoxifylline

Vinicius Rocha Santos 28 September 2010 (has links)
Introdução: A isquemia-reperfusão hepática é um fenômeno inerente aos procedimentos cirúrgicos sobre o fígado. Descrita pela primeira vez em 1975, apresenta efeitos maléficos tanto locais quanto sistêmicos que aumentam a morbidade e mortalidade dos pacientes. Dentre as formas de se atenuar o processo, a utilização de drogas anti-inflamatórias como a solução salina hipertônica a 7,5% (SSH) e a pentoxifilina vêm sendo testadas com este propósito. As duas substâncias foram utilizadas conjuntamente (HPTX) em modelos experimentais em choque hemorrágico. Contudo, na isquemia-reperfusão de origem hepática, estas foram administradas apenas isoladamente, o que torna o presente estudo pioneiro nesta avaliação. Objetivo: Avaliar os efeitos da solução salina hipertônica a 7,5% associada a pentoxifilina na isquemia-reperfusão hepática. Métodos: Foram utilizados 138 ratos Wistar divididos em quatro grupos de acordo com o tratamento empregado: GC - grupo controle (sem tratamento), SSF - solução salina fisiológica, SSH - solução salina hipertônica a 7,5% e HPTX solução salina hipertônica a 7,5% associada a pentoxifilina. A isquemia hepática foi realizada seletivamente sobre o pedículo comum do lobo mediano e ântero-lateral esquerdo pelo período de 60 minutos. As soluções foram administradas 15 minutos antes da reperfusão hepática. No sangue, foram analisadas as dosagens de transaminases hepáticas nos períodos de quatro e 12 horas e, interleucina-6 e interleucina-10 no período de 12 horas. No tecido pulmonar foram avaliadas as dosagens de azul de Evans e mieloperoxidase pulmonar nos períodos de quatro e 12 horas e, no tecido hepático do lobo isquêmico e não-isquêmico foram analisadas as dosagens de malondialdeído e a avaliação da respiração mitocondrial no período de quatro horas e a histologia nos períodos de quatro, 12 e 24 horas. Resultados: Os grupos tratados com SSH isolada ou em conjunto com a pentoxifilina apresentaram níveis significantemente menores (p<0,05) nas dosagens de transaminases e interleucina-6 em comparação aos outros dois grupos (GC e SSF). Resultados semelhantes entre os grupos foram observados no tecido pulmonar através da análise do azul de Evans e mieloperoxidase pulmonar em quatro e 12 horas e no tecido hepático com relação à respiração mitocondrial. No grupo no qual se adicionou pentoxifilina, houve diminuição estatisticamente significante da peroxidação lipídica e da permeabilidade pulmonar tardia quando comparado ao grupo SSH. Conclusões: A utilização em conjunto das duas soluções reduziu: a resposta inflamatória sistêmica; as lesões histológicas e funcionais do fígado; o estresse oxidativo e a permeabilidade pulmonar / Introduction: The liver ischemia/reperfusion (I/R) injury caused by prolonged ischemia time triggers frequently a systemic inflammatory syndrome leading to remote organ damage. Previous studies have shown that resuscitation with hypertonic saline and pentoxifylline (HPTX) attenuates hemorrhagic shock-induced injury when compared with Ringers lactate. However, it remains unclear if the HPTX protective effect occurs on liver I/R-induced injury, and if this effect overcomes the benefits of HTS used alone. Objective: Evaluated the effects of the combination of hypertonic saline solution (HTS) and pentoxifylline (PTX) on liver I/R injury in rats. Method: One hundred thirty eigth male Wistar rats underwent to one hour of partial liver ischemia performed by clamping the pedicle from the medium and left lateral lobes. Rats were divided into 4 groups: ischemia control group (C), normal saline (0.9% NaCl, 34ml/Kg) treated group (NS), hypertonic saline (7.5%NaCl, 0.4ml/Kg) treated group (HTS), and 7.5% NaCl (0.4ml/Kg) + PTX (25mg/Kg) treated group (HPTX). Samples were collected 4, 12 and 24 hours after reperfusion for determinations of serum AST, ALT, IL-6, and IL-10 levels, liver histology, liver mitochondrial oxidation and phosphorylation, and lipid peroxidation and pulmonary vascular permeability and myeloperoxidase (MPO). Results: The results showed a significant decrease in AST and ALT serum levels in HTS and HPTX groups compared to C and NS groups. Also a significant decrease in mitochondrial dysfunction was observed in HTS and HPTX groups compared to C and NS groups. The oxidative stress was significant decreased in HPTX group compared to C, NS and HTS groups in both ischemic and non-ischemic liver lobes. Elevation in serum IL-6 was significantly lower in HTS and HPTX groups compared to C and NS groups, but there was no difference in IL-10 levels. Pulmonary vascular permeability was significantly lower in groups HTS and HPTX compared with NS group, and even lower in HPTX group compared to HTS group (P < .05). Conclusion: These data suggest that addition of pentoxifylline to hypertonic saline solution decreases the inflammatory response of the liver ischemia/reperfusion injury, decreasing the liver damage as well the pulmonary injury

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