A aplicação de soluções de digluconato de clorexidina (CHX), em diferentes concentrações, tem demonstrado potencial em prevenir a progressão da erosão dentinária in situ e a diminuição, com o passar do tempo, dos valores de resistência de união (RU) de resinas compostas (RC) à dentina normal ou afetada por cárie. Entretanto, seu papel na adesão à dentina já erodida é desconhecido. Este estudo se propôs, portanto, a avaliar o efeito da aplicação de soluções de CHX em diferentes concentrações na RU de uma RC à dentina normal (parâmetro para comparações) e à dentina erodida, ao longo do tempo. Terceiros molares humanos hígidos extraídos (n=48) tiveram seu terço oclusal seccionado e as superfícies dentinárias expostas foram somente submetidas à ação de uma lixa de carbeto de silício de granulação 600/1 min (dentina normal-N, n=24), ou subsequentemente erodidas por um refrigerante a base de cola (imersões de 5 min, 3x/dia, 5 dias; dentina erodida-E, n=24). Foram, então, condicionadas (H3PO4 a 37%; 15 s), lavadas, secas e reidratadas com 1,5 L, respectivamente, de água deionizada (controle-NC, n=8 / EC, n=8), de CHX a 0,004% (N0,004%, n=8 / E0,004%, n=8) ou de CHX a 2% (N2%, n=8 / E2%, n=8). O sistema adesivo AdperTMSingle Bond 2® foi aplicado em todos os espécimes e a porção coronária foi incrementalmente reconstruída com a RC FiltekTMZ350®. Depois de armazenados em água deionizada (24 h, 37oC), os espécimes foram seccionados em palitos (secção transversal 0,81 mm2), que foram testados, sob força de tração (EMIC; célula de carga de 50 kgf; 0,5 mm/minuto), imediatamente ou depois de 6 meses ou 1 ano de envelhecimento. As falhas foram analisadas e classificadas em adesivas, mistas, coesivas em dentina ou em resina. Paralelamente, avaliou-se a qualidade da hibridização para cada grupo experimental, por meio da obtenção de imagens em microscopia confocal de varredura a laser de um espécime por grupo, hibridizado pelo mesmo adesivo, mas marcado pela adição de rodamina B, e seccionado apenas no sentido mésio-distal. Os dados obtidos da microtração foram analisados por meio dos testes de ANOVA a três critérios e de Tukey (p<0,05). Os valores médios de RU (MPa±dp; imediatamente / 6 meses / 1 ano) foram: NC (34,74±9,79 / 20,77±14,35 / 7,58±4,94); N0,004% (35,69±9,85 / 23,10±8,13 / 13,82±10,12); N2% (41,22±5,38 / 34,64±6,62 / 13,25±4,83); EC (20,94±5,37 / 7,87±8,81 / 5,43±4,99); E0,004% (22,12±7,44 / 3,47±6,25 / 4,97±3,11); E2% (15,97±5,17 / 22,23±9,12 / 5,41±5,47). Falhas adesivas e/ou mistas consistiram-se nas preponderantemente observadas. Os valores de RU da RC à dentina erodida foram sempre inferiores àqueles da RC à dentina normal. Tais valores, para ambas as condições de dentina, experimentaram redução significante com o passar do tempo, mas a aplicação da solução de CHX a 2% foi capaz de mantê-los estáveis até os 6 meses de envelhecimento dos espécimes. Portanto, a aplicação de soluções de CHX, a 2%, apresenta-se como uma estratégia promissora para conservar a RU de resinas compostas tanto à dentina normal quanto à dentina erodida. Com o tempo, no entanto, seu efeito pode tornar-se reduzido ou irrelevante. / The application of chlorhexidine digluconate (CHX) solutions, in different concentrations, has shown potential in preventing the progression of dentin erosion in situ and the decline, in the course of time, of the bond strength (BS) values of composite resins (CR) to normal or caries-affected dentin. However, its role on adhesion to already eroded dentin is unknown. This study aimed, therefore, to evaluate the effect of the application of CHX solutions in different concentrations on BS of a CR to normal (parameter for comparisons) and to eroded dentin over time. Extracted sound human third molars (n=48) had their occlusal thirds sectioned and exposed flat dentin was only submitted to a 600-grit SiC paper/1min (normal dentin- N, n=24), or subsequently eroded by a regular-cola soft-drink (5-min immersions, 3x/day, 5 days; eroded dentin-E, n=24). They were, then, acid-etched (37% H3PO4; 15 s), washed, vigorously dried, and rehydrated with 1.5 L, respectively, of deionized water (control-NC, n=8 / EC, n=8); of 0.004% CHX (N0.004%, n=8 / E0.004%, n=8); or of 2% CHX (N2%, n=8 / E2%, n=8). AdperTMSingle Bond 2® was applied in all specimens and composite core buildups were incrementally constructed with FiltekTMZ350®. After storage in deionized water (24 h, 37°C), specimens were sectioned in beams (cross-section 0.81 mm2), which were tested, under tensile (EMIC; 50 kgf load cell; 0.5 mm/minute), immediately or after 6 months or 1 year of aging. Failures were analyzed and classified in adhesive, mixed, cohesive in dentin or in resin. In parallel, the quality of the hybridization for each experimental group was evaluated, by means of the obtainment of laser scanning confocal microscopy images from one specimen per group, hybridized with the same adhesive, but marked by the addition of rhodamine B and sectioned only mesiodistally. Microtensile data were analyzed by three-way ANOVA and Tukey tests (<0.05). Mean TBS values (MPa±sd; immediately / 6 months / 1 year) were: NC (34,74±9,79 / 20,77±14,35 / 7,58±4,94); N0,004% (35,69±9,85 / 23,10±8,13 / 13,82±10,12); N2% (41,22±5,38 / 34,64±6,62 / 13,25±4,83); EC (20,94±5,37 / 7,87±8,81 / 5,43±4,99); E0,004% (22,12±7,44 / 3,47±6,25 / 4,97±3,11); E2% (15,97±5,17 / 22,23±9,12 / 5,41±5,47). Adhesive and/or mixed failures consisted in the mainly observed ones. BS values of the CR to the eroded dentin were always lower than that of the CR to the normal dentin. These values, to both dentin conditions, experienced a significant reduction in the course of time, but application of the 2% CHX solution was able to keep them stable until 6-months aging of the specimens. Therefore, the application of CHX solutions, at 2%, is presented as a promising strategy to conserve BS both to normal and to eroded dentin. Over time, however, its effect may become reduced or irrelevant.

Diabetic symmetrical polyneuropathy is the most common secondary complication of diabetes, with no effective treatment, apart from maintaining tight glycemic control. It is therefore essential to understand the mechanisms underlying the pathogenesis of the disease in order to develop new therapeutic strategies. Biochemical and structural changes are observed in the extracellular matrix (ECM) of the peripheral nerve in diabetes: including increased endoneurial collagen; reduplication of basement membranes around endoneurial capillaries; a thickening of basal lamina; and accumulation of advanced glycation end-products (AGEs). In normal nerves, ischaemic or other damage to distal axons provokes a regenerative response; in diabetes this is abortive and failure of axonal regeneration is a hallmark of clinical and experimental diabetic neuropathy. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes that cleave the protein components of the ECM. MMP-2 and MMP-9 play a central role in Wallerian degeneration and regeneration following nerve injury. This thesis investigates whether MMP-2 and -9 expression and/or activity were altered in the peripheral nerve in diabetes, and could contribute to regenerative failure in diabetic neuropathy. Using an experimental model of diabetes, we have demonstrated that MMP-2, but not MMP-9, is upregulated at gene, protein and activity levels in the rat sciatic nerve 8 weeks post-streptozotocin (STZ). This upregulation was not maintained at later time-points of diabetes. In vitro sciatic nerve cryoculture studies showed that peripheral nerve from STZ-diabetic rats was less supportive for neurite outgrowth from dissociated adult rat sensory neurons than nerve obtained from age-matched control rats. Cyrocultures were pre-treated with either MMP-2 or chondroitinase ABC, remodelling the peripheral nerve ECM, via the removal of inhibitory chondroitin sulfate proteoglycans from the sciatic nerve, and significantly enhanced its ability to support axonal regeneration, and partially restored the diabetes-associated regenerative deficit. However, exogenous MMP-2 or MMP-9 did not directly affect neurite outgrowth of dissociated adult rat sensory neurons. Finally, we assessed the neuroprotective effects of the AGE inhibitors LR90 and pyridoxamine in experimental diabetes, using a number of electrophysiological, behavioural and biochemical endpoints. These inhibitors were effective at preventing the development of some of the functional deficits observed in STZ-diabetes. Sensory nerve conduction velocity deficits and lipid peroxidation in the sciatic nerve were prevented by both LR90 and pyridoxamine. These agents have potential for the treatment of diabetic neuropathy.

Metaloproteinases da matriz extracelular (MMPs) são uma família de endopeptidases zinco-dependentes conhecidas por degradar componentes do tecido conjuntivo em processos fisiológicos e patológicos. A regulação da atividade das MMPs pode ser feita pelos inibidores teciduais de metaloproteinases (TIMPs). A doença periodontal (DP) é a inflamação crônica em que atividade excessiva das MMPs e mieloperoxidase (MPO) são apontadas como responsáveis pela destruição dos tecidos suporte dos dentes. Os componentes da saliva são derivados da vascularização local sendo possível encontrar neste fluido o reflexo de muitas moléculas presentes no plasma. Desta forma, os objetivos deste trabalho foram: 1) Comparar os níveis de MMPs, TIMPs e MPO na saliva total estimulada (STE) e plasma de pacientes com DP antes (DA) e após (DT) o tratamento periodontal não cirúrgico, e em voluntários saudáveis no início do estudo (CA) e após 3 meses (CT); 2) Avaliar se existe correlação entre os resultados. Foram realizadas as dosagens de MMP-8, MMP-9, TIMP-1 e TIMP-2 pelo método de ELISA; a atividade gelatinolítica das formas da MMP-9 por zimografia; e a atividade da MPO por ensaio colorimétrico. Houve uma menor atividade gelatinolítica, assim como menores concentrações de MMP-8 e TIMP-2 na STE de DT quando comparadas a DA (p < 0,05). A atividade de MPO foi superior no grupo DA em relação a CA (p < 0,05). Foram encontradas correlações moderadas e estatisticamente significantes entre a MMP-9 quantificada por ELISA no plasma e todos os parâmetros resultantes da zimografia de STE, isto é, MMP-9 de massa molecular de 92 kDa (r = 0,37, p = 0,002), 130 kDa (r = 0,35, p =0,003 ), a soma da sua atividade gelatinolítica (130 + 92 kDa) (r = 0,43, p = 0,0002), gelatinase de 180 kDa (r = 0,35, p = 0,003), e soma da atividade gelatinolítica total (180+130+92 kDa ) (r = 0,37, p = 0,002). A MMP-8 plasmática apresentou correlação com a atividade gelatinolítica das bandas de 92 kDa (r = 0,30 e p = 0,01) e soma da atividade gelatinolítica (130 + 92 kDa) (r = 0,24 e p= 0,04) presentes na STE. Também foi possível observar uma correlação fraca entre a atividade gelatinolítica da MMP-9 de 92 kDa do plasma e a atividade gelatinolítica da banda de 180 kDa (r = 0,26 e p = 0,03), e uma correlação moderada entre o TIMP-2 do plasma e o TIMP-2 da STE (r = 0,32 e p =0,04). Os resultados mostram que a atividade gelatinolítica da STE pode estar refletindo as concentrações de marcadores inflamatórios sistêmicos tais como a MMP-8 e MMP-9, assim como a concentração de TIMP-2 na STE pode estar refletindo a concentração de TIMP-2 circulante. A avaliação conjunta destes resultados sugere que existe uma atenuação de alguns dos marcadores inflamatórios analisados na STE e no plasma após o tratamento da DP, e que os níveis salivares e plasmáticos de alguns destes marcadores se correlacionam. Como a coleta de saliva é menos invasiva, mais estudos sobre a correlação destes marcadores nestes dois fluidos pode ser muito interessante. / Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to cleave components of the connective tissue in physiological and pathological processes. The regulation of MMP activities is done by the tissue inhibitors of metalloproteinases (TIMPs). Periodontal disease (PD) is a chronic inflammation with excessive activity of MMPs, which degrade the tooth supporting tissues. The saliva components are derived from the local blood supply, and this fluid may therefore reflect the plasma. So, the objectives of this study were: 1) to compare the levels of MMPs, TIMPs and MPO in stimulated whole saliva (SWS) and plasma of PD patients before (PB) and 3 months after (PT) the non-surgical periodontal treatment, and in healthy volunteers at baseline (CB) and 3 months after baseline (CT), and 2) to evaluate the correlations between the results found. Measurements of MMP-8, MMP-9, TIMP-1 and TIMP-2 were performed by ELISA. Gelatinolitic activity of MMP-9 forms were determined by zymography, and the MPO activity was determined by colorimetric assay. There was lower gelatinolitic activity, and lower concentrations of MMP-8 and TIMP-2 in SWS on PT group compared with PB group (p <0.05). MPO activity was higher in PB compared to CB (p <0.05). Statistically significant moderate correlations were observed in all associations between MMP-9 performed by ELISA in plasma and gelatinolitic activity bands of STE: MMP-9 molecular form of 92 kDa (r = 0,37, p = 0,0017), MMP-9 molecular form of 130 kDa (r = 0,35, p = 0,003), the sum of its gelatinase activity (130 +92 kDa) (r = 0,43, p = 0,0002), gelatinase of 180 kDa (r = 0,35, p = 0,003), and the sum of total gelatinase activity (180+130+92 kDa) (r = 0,37, p = 0,002). Circulating MMP-8 levels correlate with salivary gelatinase activity bands of 92 kDa (r = 0,30, p = 0,01) and the sum of gelatinase activity (130 +92 kDa) (r = 0,24, p = 0,04). In addition, a weak correlation between gelatinase activity of plasmatic 92 kDa MMP-9 and gelatinase of 180 kDa in SWS (r= 0,26 p = 0,03) was found, and a moderate correlation between plasmatic TIMP-2 and TIMP-2 of SWS (r = 0,32, p = 0,004). The results show that the gelatinase activity of SWS may reflect the concentrations of systemic inflammatory markers such as MMP-8 and MMP-9, also the concentration of TIMP-2 in the SWS may reflect the circulating concentration of TIMP-2. The evaluation of these results suggests that there is an attenuation of some inflammatory markers analyzed in the SWS and in plasma after treatment of PD. Furthermore, there are correlations between salivary and plasma levels in some of these markers. Because saliva sampling is less invasive, more studies about the correlations between these markers in these two fluids are necessary.

Orientador: Carlos Alan Candido Dias Junior / Resumo: O presente estudo teve por objetivo investigar e comparar as alterações relacionadas à reatividade vascular e aos biomarcadores de estresse oxidativo e da inflamação em ratos anestesiados com isoflurano ou sevoflurano. Para alcançar nossos objetivos, ratos Wistar machos adultos foram distribuídos aleatoriamente em três grupos experimentais: não anestesiado (grupo controle) e anestesiados com isoflurano (grupo Iso) ou sevoflurano (grupo Sevo). A responsividade vascular à fenilefrina (PHE) e acetilcolina (ACh) na presença ou ausência de éster N-nitro-L-arginina-metílico (L-NAME) foram avaliadas em anéis de aorta torácica com endotélio intacto (E +) e endotélio desnudo (E-). Os metabólitos do óxido nítrico (NO) (NOx), a peroxidação lipídica, a função antioxidante, os níveis de citocinas e a atividade das metaloproteinases de matriz extracelular (MMPs) também foram avaliados. Nenhuma diferença significativa foi observada com relação aos dados hemodinâmicos e temperatura entre os grupos anestesiados. Nos anéis com endotélio intacto, a anestesia com o sevoflurano reduziu a vasoconstrição induzida pela PHE e pelo KCL quando comparado ao grupo controle e Iso, respectivamente (P ˂ 0.05). O isoflurano aumentou significativamente a vasoconstrição induzida pela PHE e pelo KCl, nos anéis com endotélio desnudo (P ˂ 0.05). Níveis de NO reduzidos foram observados após a anestesia com sevoflurano (P = 0.01), mas não com isoflurano. O estresse oxidativo foi significativamente aumentado em ambo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The current study aimed to investigate and compare the changes on vascular reactivity, biomarkers of oxidative stress and inflammation of rats anesthetized with isoflurane or sevoflurane. Adult Wistar rats were assigned to three experimental groups (n = 6 per group): Non-anesthetized (Control group) and anesthetized with isoflurane (Iso group) or sevoflurane (Sevo group). Vascular responsiveness to phenylephrine (PHE) and acetylcholine (ACh) in the presence or absence of Nω-nitro-L-arginine-methyl ester (L-NAME) was evaluated in thoracic aortic rings with intact endothelium (E+) and denuded endothelium (E-). Nitric oxide (NO) metabolites (NOx), lipid peroxidation, antioxidant function, cytokines levels and matrix metalloproteinases (MMPs) activity were also assessed. In intact endothelium-aortic rings sevoflurane impairs PHE-induced vasoconstriction versus control group and reduces KCl-induced vasoconstriction versus Iso group (P ˂ 0.05). In denuded endothelium-aortic rings isoflurane increases vasoconstriction induced by both PHE and KCl (P ˂ 0.05). Sevoflurane, but not isoflurane, reduces NO (P = 0.01). Oxidative stress was increased in Sevo and Iso groups (P ˂ 0.05). While sevoflurane reduced IL-10 and IL-1β, isoflurane increased IL-1β. MMP-2 activity in aorta was increased in Sevo (P ˂ 0.05), but not in Iso group. We concluded that 150 minutes of anesthesia with sevoflurane, but not with isoflurane, impairs vascular responsiveness to vasoconstrictors agents. Also, while b... (Complete abstract click electronic access below) / Doutor

Orientador: Fernanda Gonçalves Basso / Resumo: A mucosite é um dos principais efeitos adversos do tratamento oncológico e apresenta influência significativa na morbidade e qualidade de vida dos pacientes submetidos a este tipo de tratamento. A etiopatogenia desta condição vem sendo relacionada não só a toxicidade direta dos quimioterápicos e radiação ionizante, mas também a uma ativação exacerbada da resposta inflamatória dos tecidos. Recentemente, o desenvolvimento e a severidade da mucosite oral também tem sido relacionada a expressão exacerbada de metaloproteinases (MMPs), que resulta na desorganização dos tecidos epitelial e conjuntivo e consequentemente, em atraso do processo de reparo. O manejo da mucosite oral tem sido baseado na utilização de agentes analgésicos tópicos, antibióticos e antifúngicos, bem como na aplicação da laserterapia de baixa intensidade (LBI). A LBI apresenta resultados positivos sobre as lesões de mucosite oral, porém, esta modalidade terapêutica requer a utilização de um equipamento de custo moderado e deve ser feita sob supervisão. Desta forma, novas estratégias preventivas e terapêuticas, que possam atuar na modulação da resposta inflamatória e na expressão de MMPs para diminuir a incidência e a severidade das lesões de mucosite oral e também acelerar o processo de reparo têm sido propostas. Estudos recentes demonstraram a efetividade de compostos naturais, como as antocianinas, na redução da incidência e severidade destas lesões. O objetivo desta pesquisa in vitro foi avaliar comparativam... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Mucositis is the major adverse effect of oncological treatment and presents huge impact on oncological patients' morbidity and quality of life. Etiopathogenesis of oral mucositis has been not only related to a direct toxicity of chemotherapy drugs and radiant therapy, but also to an extended inflammatory reaction. Recently, development and severity of oral mucositis has also been associated to increased expression of metalloproteinases (MMPs), that results in disorganization of epithelial and connective tissues, leading to a delayed tissue healing. Treatment of oral mucositis is based on the application of topic analgesic and antimicrobial compounds, as also low-level lasertherapy (LLLT). LLLT shows positive outcomes on oral mucositis, however, this therapy requires the use of a moderate cost equipament and professional supervision. Therefore, new preventive and therapeutic strategies that can act on the modulation of inflammatory response as well as on MMPs expression could decrease the incidence and severity of oral mucositis, therefore enhancing oral mucosa healing. Recent studies demonstrated the effectiveness of natural compounds, such as antocyanins on the decreased incidence and severity of these lesions. Consequently, the aim of the present in vitro study were to assess the effects of proanthocyanidins (PAs, grape seed extract), naringenin (NA, proanthocyanidins-derived synthetic compound), also denominated flavanones, and LLLT as modulators for synthesis of interleukin-6 and MMPs from gingival fibroblasts. Cells were isolated from the papillary gingival tissue of a young (24 years) and healthy individual by enzymatic digestion, then cultured and submitted to different treatments. The influence of two chemotherapeutic agents (5-fluorouracil - 5-FU and methotrexate - MTX) and inflammatory cytokines (TNF-α, IL-6 and -8) on the induction of MMP-2 and -9 synthesis and gene expression were ... (Complete abstract electronic access below) / Mestre

Initialement, la vision restreinte des MMPs en tant que de simples « destructeurs » de la matrice extracellulaire avait largement sous-estimé limportance et la diversité de leurs contributions aux différentes étapes de la progression tumorale et de la dissémination métastatique. Ces dernières années, les fonctions complexes des MMPs dans la progression tumorale ont été renforcées par la découverte de nombreux nouveaux substrats dégradés, clivés ou activés par les MMPs, incluant non seulement des composants de la matrice extracellulaire mais aussi des récepteurs, des molécules dadhésion et de nombreuses molécules potentiellement bioactives. La complexité et la diversité de laction des MMPs dans la progression tumorale fournissent certaines explications quant à « léchec thérapeutique » de linhibition des MMPs dans les études cliniques de cancers humains. Une compréhension complète et spécifique de la biologie de chaque MMP est néanmoins requise avant de les considérer à nouveau comme des cibles thérapeutiques contre le cancer ou dautres pathologies. Les travaux réalisés dans le cadre de ce doctorat ont contribué à la compréhension des mécanismes moléculaires impliquant la MT1-MMP dans la croissance et langiogenèse tumorale et ont identifié, pour la première fois, une implication de la MT4-MMP dans la croissance tumorale et la dissémination métastatique du cancer du sein. Malgré sa faible activité de dégradation de la matrice extracellulaire, cette protéase à lien glycosylphosphatidyl inositol pourrait promouvoir la progression tumorale en affectant la structure des vaisseaux sanguins intratumoraux.

Thèse de doctorat : Médecine. Biochimie : Reims : 2001. / 2001REIMM201. Bibliogr. :153-176 f.

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Includes bibliographical references. Also available online.

Previous studies have shown that ischemia-reperfusion (I/R) injury is associated with cardiac dysfunction and depression in sarcolemmal Na+-K+-ATPase activity. This study was undertaken to evaluate the role of proteases in these alterations by subjecting rat hearts to different times of global ischemia, and reperfusion after 45 min of ischemia. Decreases in Na+-K+-ATPase activity at 60 min of global ischemia were associated with augmented activities of both calpain and MMPs and depressed protein content of β1- and β2-subunits, without changes in α1- and α2-subunits of the enzyme. However, reperfusion of ischemic heart produced depression in Na+-K+-ATPase activity, no change in the augmented calpain activity, but decreases in augmented MMP-2 activity and Na+-K+-ATPase content. MDL28170, a calpain inhibitor, was more effective in attenuating I/R-induced alterations than doxycycline, an MMP inhibitor. Incubation of control SL preparation with calpain, unlike MMP-2, depressed Na+-K+-ATPase activity and decreased α1, α2 and β2 without changes in β1. These results support the view that activation of calpain is involved in depressing Na+-K+-ATPase activity and degradation of its subunits in hearts subjected to I/R injury.

Previous studies have shown that ischemia-reperfusion (I/R) injury is associated with cardiac dysfunction and depression in sarcolemmal Na+-K+-ATPase activity. This study was undertaken to evaluate the role of proteases in these alterations by subjecting rat hearts to different times of global ischemia, and reperfusion after 45 min of ischemia. Decreases in Na+-K+-ATPase activity at 60 min of global ischemia were associated with augmented activities of both calpain and MMPs and depressed protein content of β1- and β2-subunits, without changes in α1- and α2-subunits of the enzyme. However, reperfusion of ischemic heart produced depression in Na+-K+-ATPase activity, no change in the augmented calpain activity, but decreases in augmented MMP-2 activity and Na+-K+-ATPase content. MDL28170, a calpain inhibitor, was more effective in attenuating I/R-induced alterations than doxycycline, an MMP inhibitor. Incubation of control SL preparation with calpain, unlike MMP-2, depressed Na+-K+-ATPase activity and decreased α1, α2 and β2 without changes in β1. These results support the view that activation of calpain is involved in depressing Na+-K+-ATPase activity and degradation of its subunits in hearts subjected to I/R injury.