Estresse oxidativo em ovinos das raças Suffolk e Santa Inês experimentalmente infectados por Haemonchus contortus

Pós-graduação em Ciência Animal - FMVA

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiopulmonary bypass: development of John Gibbon's heart-lung machine

To provide a brief review of the development of cardiopulmonary bypass. A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation. The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies. Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function.

The role of renin-angiotensin system in the chronic allograft nephropathy: an immunohistochemical study

Evidences suggest a role of renin-angiotensin system (RAS) in the development of chronic allograft injury. We correlated intrarenal angiotensin-converting enzyme, angiotensin II (Angio II) and transforming growth factor β1 (TGFβ1) expression in 58 biopsies-proven chronic allograft nephropathy (CAN) with tissue injury and allograft survival. The biopsies with CAN were graded according to Banff classification as I (22 cases), II (17) and III (19); 27 biopsies also showed a mononuclear inflammatory infiltrate in scarred areas. There were increased expression of angiotensin converting-enzyme (ACE), Angio II and TGFβ1 mainly in tubulointerstitial compartment in the group with CAN; there was no association of Angio II and TGFβ1 expression with interstitial fibrosis. There were no significant differences of ACE, Angio II and TGFβ1 expression between the patients treated and untreated with RAS blockade, and with the graft outcome. Interstitial inflammatory infiltrate had positive correlation with interstitial fibrosis and significant impact on graft survival at 8 years. Our study showed in a group of cases with CAN a high percentage of inflammatory infiltrate that correlated with interstitial fibrosis and graft outcome. The chronic inflammatory changes in these cases did not show significant association with local RAS expression.

Papel dos receptores TLR2 e TLR4 na produção de citocinas em pacientes chagásicos crônicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise do padrão de resposta Th17 e de células T regulatórias em pacientes com a forma digestiva da doença de Chagas crônica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute phase response following ovariohysterectomy in female dogs

The concentrations of acute phase proteins are correlated with the severity of the surgical trauma, being elevated when severe tissue injury is produced. The aim of this study was to evaluate the leukogram and the acute phase proteins concentrations in healthy female dogs submitted to minimally invasive ovariohysterectomy, with the use of nylon cable ties (G1), and conventional (laparotomy) ovariohysterectomy, with the use of nylon suture (G2), as methods to ligate the ovarian pedicles and uterine body, respectively. Blood samples from 30 adult healthy female dogs (15 for each group) were obtained before surgery, and at 24 and 48 h and 7 days after surgery. Serum protein fractions were determined by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis. Neutrophilia was observed 24 h after both surgical procedures but did not differ (P ≥ 0.05) between the groups. In G1, the estimated concentration of ceruloplasmin increased (P ≤ 0.05) 48 h after the surgical procedure. The estimated ceruloplasmin concentration was significantly higher in G1 (P ≤ 0.05) when compared to G2 48 h postoperatively, and the estimated haptoglobin concentration was also significantly greater in G1 (P ≤ 0.05) than in G2 from 24 h to 7 days after surgery. Through the ceruloplasmin and haptoglobin estimated concentrations, we conclude that the minimally invasive ovariohysterectomy caused a more intense inflammatory response, which was not reflected in the white blood cell count.

Análise comparativa da incidência de hemólise e resposta inflamatória sistêmica induzida pela circulação extracorpórea em bomba de roletes e em bomba centrífuga em cirurgia de revascularização do micárdio

Pós-graduação em Bases Gerais da Cirurgia - FMB

Análise comparativa da incidência de hemólise e resposta inflamatória sistêmica induzida pela circulação extracorpórea em bomba de roletes e em bomba centrífuga em cirurgia de revascularização do micárdio

Pós-graduação em Bases Gerais da Cirurgia - FMB

Augmented nitric oxide production and up-regulation of endothelial nitric oxide synthase during cecal ligation and perforation

Nitric oxide (NO) has been pointed out as being the main mediator involved in the hypotension and tissue injury taking place during sepsis. This study aimed to investigate the cellular mechanisms implicated in the acetylcholine (ACh)-induced relaxation detected in aortic rings isolated from rats submitted to cecal ligation and perforation (CLP group), 6 h post-CLP. The mean arterial pressure was recorded, and the concentration-effect curves for ACh were constructed for endothelium-intact aortic rings in the absence (control) or after incubation with one of the following NO synthase inhibitors: L-NAME (non-selective), L-NNA (more selective for eNOS), 7-nitroindazole (more selective for nNOS), or 1400W (selective for iNOS). The NO concentration was determined by using confocal microscopy. The protein expression of the NOS isoforms was quantified by Western blot analysis. The prostacyclin concentration was indirectly analyzed on the basis of 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) levels measured by enzyme immunoassay. There were no differences between Sham- and CLP-operated rats in terms of the relaxation induced by acetylcholine. However, the NOS inhibitors reduced this relaxation in both groups, but this effect remained more pronounced in the CLP group as compared to the Sham group. The acetylcholine-induced NO production was higher in the rat aortic endothelial cells of the CLP group than in those of the Sham group. eNOS protein expression was larger in the CLP group, but the iNOS protein was not verified in any of the groups. The basal 6-keto-PGF(1 alpha) levels were higher in the CLP group, but the acetylcholine-stimulated levels did not increase in CLP as much as they did in the Sham group. Taken together, our results show that the augmented NO production in sepsis syndrome elicited by cecal ligation and perforation is due to eNOS up-regulation and not to iNOS. (C) 2012 Elsevier Inc. All rights reserved.

Ethanol consumption increases the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and metalloproteinases in the rat kidney

Objectives The effects of longterm ethanol consumption on the levels of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS) and metalloproteinase-2 (MMP-2) were studied in rat kidney. Methods Male Wistar rats were treated with 20% ethanol (v/v) for 6 weeks. Nitrite and nitrate generation was measured by chemiluminescence. Protein and mRNA levels of eNOS and iNOS were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. MMP-2 activity was determined by gelatin zymography. Histopathological changes in kidneys and indices of renal function (creatinine and urea) and tissue injury (mitochondrial respiration) were also investigated. Results Chronic ethanol consumption did not alter malondialdehyde levels in the kidney. Ethanol consumption induced a significant increase in renal nitrite and nitrate levels. Treatment with ethanol increased mRNA expression of both eNOS and iNOS. Immunohistochemical assays showed increased immunostaining for eNOS and iNOS after treatment with ethanol. Kidneys from ethanol-treated rats showed increased activity of MMP-2. Histopathological investigation of kidneys from ethanol-treated animals revealed tubular necrosis. Indices of renal function and tissue injury were not altered in ethanol-treated rats. Conclusions Ethanol consumption increased renal metalloproteinase expression/activity, which was accompanied by histopathological changes in the kidney and elevated NO generation. Since iNOS-derived NO and MMPs contribute to progressive renal injury, the increased levels of NO and MMPs observed in ethanol-treated rats might contribute to progressive renal damage.

Kinin-B2 Receptor Mediated Neuroprotection after NMDA Excitotoxicity Is Reversed in the Presence of Kinin-B1 Receptor Agonists

Background: Kinins, with bradykinin and des-Arg(9)-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg(9)-bradykinin as well as Lys-des-Arg(9)-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-Daspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Principal Findings: Bradykinin at 10 nM and 1 mu M concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg(9)-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059,showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. Conclusions: Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg(9)-bradykinin by carboxypeptidases, present in different areas including in brain, our results provide a mechanism for the neuroprotective effect in vitro despite of the deleterious effect observed in vivo.

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.

Occlusal trauma can not be compared to orthodontic movement or Occlusal trauma in orthodontic practice and V-shaped recession

The mechanisms of tissue changes induced by occlusal trauma are in no way comparable to orthodontic movement. In both events the primary cause is of a physical nature, but the forces delivered to dental tissues exhibit completely different characteristics in terms of intensity, duration, direction, distribution, frequency and form of uptake by periodontal tissues. Consequently, the tissue effects induced by occlusal trauma are different from orthodontic movement. It can be argued that occlusal trauma generates a pathological tissue injury in an attempt to adapt to new excessive functional demands. Orthodontic movement, in turn,performs physiological periodontal bone remodeling to change the position of the teeth in a well-planned manner, eventually restoring normalcy.

Sindrome da Asfissia Perinatale nel puledro neonato: protocolli diagnostico-terapeutici

La Sindrome da Asfissia Perinatale (PAS) è una delle più comuni patologie che colpiscono il puledro neonato nelle prime 72 h di vita. È una patologia difficile da diagnosticare in quanto non esistono parametri o segni clinici specifici, la sintomatologia è molto variabile in base alla durata e all’intensità dell’insulto ipossico ischemico e al tipo di organo maggiormente colpito. Lo scopo di questo studio è la ricerca e la valutazione di alcuni parametri biochimico-clinici e di alcuni biomarkers per la diagnosi precoce e il corretto trattamento dei puledri affetti da PAS. Nei puledri neonati che presentano questa patologia è stata riscontrata un’ipermagnesiemia al momento del ricovero associata a prognosi infausta, probabilmente causata da un grave danno cellulare con rilascio in circolo del magnesio intracellulare. La PAS potrebbe essere un’ulteriore causa di Euthyroid Sick Syndrome, in quanto abbiamo riscontrato una diminuzione delle concentrazioni di T3 e T4 nei puledri malati rispetto ai sani della stessa età, come avviene in altre malattie sistemiche. Lo studio del profilo proteomico ha permesso di separare le più importanti frazioni proteiche del liquido amniotico di cavalla, mettendo in evidenza similitudini e differenze qualitative e quantitative nei ferogrammi dei puledri sani e di quelli affetti da PAS ed una maggiore variabilità è stata riscontrata nei profili dei liquidi amniotici dei puledri malati. Il glutatione è risultato poco espresso nel puledro neonato, i puledri sani presentano concentrazioni più basse sia rispetto ai malati della stessa età sia agli adulti ma con una tendenza all’aumento nelle prime 24 ore di vita per i sani ed un calo nei malati. La somministrazione della terapia antiradicalica non influisce sulle concentrazioni di glutatione totale ed i puledri deceduti presentano concentrazioni più alte.