29 research outputs found

    Assessment of circulating concentrations of proinflammatory and anti-inflammatory cytokines and nitric oxide in dogs with brachycephalic airway obstruction syndrome

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    Objective—To evaluate plasma concentrations of inflammatory mediators in dogs with brachycephalic airway obstruction syndrome, identify a possible role for these mediators in the syndrome, and investigate the relationship between plasma concentrations of inflammatory mediators and severity of clinical signs. Animals—17 dogs with brachycephalic airway obstruction syndrome and 10 mesocephalic (control) dogs. Procedures—A blood sample was collected once from each dog. Plasma concentrations of interleukin (IL)-1ÎČ, tumor necrosis factor (TNF)-α, IL-6, IL-17A, IL-10, and IL-13 were measured with ELISAs. Nitric oxide (NO) concentrations were determined with a Griess test. For analysis, brachycephalic dogs were categorized into groups depending on weight (smal [< 16 kg]) and large [≄ 16 kg]) or on whether they required medical or surgical treatment. Results—Compared with control dog values, plasma concentrations of TNF-α, IL-10, IL-13, and IL-17A were significantly higher in brachycephalic dogs and markedly so for brachycephalic dogs that required surgery; findings for small and large brachycephalic dogs did not differ. A similar pattern of differences between control and brachycephalic dogs was dentified for plasma NO concentration. Plasma IL-1ÎČ and IL-6 concentrations in control and brachycephalic dogs did not differ. Conclusions and Clinical Relevance—In brachycephalic dogs, plasma TNF-α, IL-10, IL-13, L-17A, and NO concentrations were higher than values in control dogs and appeared to be associated with disease severity. These variables may be useful as indicators of inflammatory processes associated with brachycephalic airway obstruction syndrome in dogs.Depto. de BioquĂ­mica y BiologĂ­a MolecularFac. de MedicinaTRUEpu

    Effect of a Combined Treatment With Growth Hormone and Melatonin in the Cardiological Aging on Male SAMP8 Mice

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    The effect of a chronic combined treatment with growth hormone (GH) plus melatonin (Mel) on different age-related processes in cytosolic and nuclear fractions of hearts from SAMP8 mice (2 and 10 months) has been investigated. The parameters studied have been messenger RNA expressions of IL-1, IL-10, NFkBp50, NFkBp52, TNFα, eNOS, iNOS, HO-1, HO-2, BAD, BAX, and Bcl2 and protein expressions of iNOS, eNOS, TNFα, IL-1, IL-10, NFkBp50, NFKbp52, and caspase activity (3 and 9). Our results supported the existence of a proapoptotic and oxidative status together with inflammatory processes in the heart of old mice, with increases of inflammatory cytokines, caspase activity, HO-1, BAX, NFkBp50, and NFkBp52 and decreases of eNOS and Bcl2. Also, we were able to observe the translocation of NFkB to nuclei. The combined treatment was able to partially reduce the incidence of these deleterious changes, showing differences with the separated treatments with GH and Mel as were investigated in previous articles from our group.Instituto de Salud Carlos IIIJunta de AndalucĂ­aMinisterio de Educación y CienciaDepto. de FisiologĂ­aFac. de MedicinaTRUEpu

    Effect of growth hormone treatment on pancreatic inflammation, oxidative stress, and apoptosis related to aging in SAMP8 mice

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    Aging is associated with an increase in inflammation, oxidative stress, and apoptosis. Furthermore, aging is accompanied by an alteration of the growth hormone (GH) -insulin-like growth factor-1 (IGF-1) axis. The aim of this study was to examine the regulation of these parameters in the pancreas of old mice and how GH treatment could affect this process. Male senescence-accelerated prone mice (SAMP8) and male senescence-accelerated resistant mice (SAMR1) 2 (young) and 10 months old were used (n = 40). Animals were divided into five experimental groups: 1 and 2, SAMP8/R1 young control; 3 and 4, SAMP8/R1 old control (untreated); and 5, SAMP8 old treated with GH. Physiologically equivalent doses of GH were administered for 1 month (2 mg subcutaneously [s.c.]/kg/day) and several parameters were analyzed. Aging was associated with increased inflammation, oxidative stress, and apoptosis (increased tumor necrosis factor-α [TNF-α], interleukin-ÎČ [IL-ÎČ], IL-6, monocyte chemoattractant protein-1 [MCP1], IL-2, heme oxygenase [HO-1], inducible nitric oxide synthase [iNOS], and nitric oxide metabolites [NOx]). The ratio of anti/pro apoptotic mRNA expression-B cell lymphoma 2 (Bcl-2) Bcl-2-associated X protein (BAX) + Bcl-xL/Bcl-2-associated death promoter (BAD)-was decreased during aging in SAMP8 mice. X-inhibitor of apoptosis (XIAP) was decreased during the aging process. Furthermore, no changes were observed in protein expression of nuclear factor-ÎșB (NF-ÎșB p65 and NF-ÎșBp50-105. However, the protein expression of NF-ÎșB p52-100 and inhibitor kappa B (IÎșB) alpha was increased with age in the pancreas of SAMP8 mice. On the other hand, the expression of IÎșB beta was decreased with aging. These results indicate that aging is associated with significant alterations in the relative expression of pancreatic genes involved in inflammation, oxidative stress, and apoptosis. According to our results, GH administration to old SAMP8 mice was able to improve pancreas from this parameters.Instituto de Salud Carlos IIIJunta de AndalucĂ­aDepto. de FisiologĂ­aFac. de MedicinaTRUEpu

    Effect of chronic melatonin administration on several physiological parameters from old Wistar rats and SAMP8 mice

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    The effect of melatonin administration on age-induced alterations in hepatocytes, central nervous system, immune system, and skin are reviewed. Twenty-two-month-old Wistar rats and SAMP8 (senescence prone) mice of 10 months of age were used as experimental models. Wistar rats were analyzed untreated or after the chronic administration of melatonin at a dose of 1 mg/kg/day in the drinking water for 10 weeks. At the end of the treatment period, the various parameters were investigated. Results were compared with those of 2-month-old controls. In hepatocytes, aging induced a significant increase in oxidative stress, inflammation, and apoptosis when compared to young animals. Melatonin administration significantly ameliorated all these age-related changes. The impairment of the cardiovascular system with aging appears to contribute to the increased morbidity and mortality of the aged subjects. The process was investigated in SAMP8 mice of 10 months of age. Melatonin was provided for 30 days at two different dosages (1 mg/kg/day and 10 mg/kg/day), also in the drinking water. After treatment, the expression of inflammatory mediators (tumor necrosis factor-α, interleukin 1 and 10, NFÎșBp50 and NFÎșBp52), apoptosis markers (BAD, BAX, and Bcl2), and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart. Inflammation as well as oxidative stress and apoptosis markers were increased in old SAMP8 males, as compared to young controls. After treatment with melatonin, these age-altered parameters were partially reversed. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin is able to reduce these parameters. In the skin, a reduction of epidermal thickness together with a marked increase of the hypodermis with great fat accumulation was observed in old rats, together with an increase in caspase 3, 8 of nucleosomes and LPO and a reduction in Bcl2 levels in the cultured keratinocytes. Melatonin treatment was able to reduce the fat content of the hypodermis and to increase Bcl2 and reduce nucleosomes, caspases, and LPO in keratinocytes. Conclusion: Melatonin administration exerts a beneficial effect against age-induced changes in several physiological parameters in Wistar rats and SAMP 8 mice.Instituto de Salud Carlos IIIDepto. de FisiologĂ­aFac. de MedicinaTRUEpu

    Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8)

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    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was decreased with aging in SAMP8 and increased in SAMR1 mice. Expressions of glucagon and GLUT2 messenger RNAs (mRNAs) were increased with aging in SAMP8 mice, and no differences were observed in somatostatin and insulin mRNA expressions. Furthermore, aging decreased also the expressions of Pdx-1, FoxO 1, FoxO 3A and Sirt1 in pancreatic SAMP8 samples. Pdx-1 was decreased in SAMR1 mice, but no differences were observed in the rest of parameters on these mice strains. Treatment with melatonin was able to decrease plasma insulin levels and to increase its pancreatic content in SAMP8 mice. In SAMR1, insulin pancreatic content and plasma levels were decreased. HOMA-IR was decreased with melatonin treatment in both strains of animals. On the other hand, in SAMP8 mice, treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin mRNA. Furthermore, it was also able to increase the expression of Sirt1, Pdx-1 and FoxO 3A. According to these results, aging is associated with significant alterations in the relative expression of pancreatic genes associated to glucose metabolism. This has been especially observed in SAMP8 mice. Melatonin administration was able to improve pancreatic function in old SAMP8 mice and to reduce HOMA-IR improving their insulin physiology and glucose metabolism.Instituto de Salud Carlos IIIJunta de AndalucĂ­aDepto. de FisiologĂ­aFac. de MedicinaTRUEpu

    Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model†

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    OBJECTIVES: Lung ischaemia/reperfusion (IR) induces a systemic inflammatory response that causes damage to remote organs. The liver is particularly sensitive to circulating inflammatory mediators that occur after IR of remote organs. Recently, remote ischaemic preconditioning has been proposed as a surgical tool to protect several organs from IR. The present study was designed to investigate a possible protective effect of lung ischaemic preconditioning (IP) against the liver inflammatory response to lung IR. METHODS: Two groups [IP and control (CON)] of 10 Large White pigs underwent lung autotransplants (left pneumonectomy, ex situ cranial lobectomy and caudal lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two 5-min cycles of left pulmonary arterial occlusion and a 5-min interval of reperfusion between the two occlusions. Five animals underwent sham surgery. Liver biopsies were obtained during surgery at (i) prepneumonectomy, (ii) prereperfusion, (iii) 10 min after reperfusion of the implanted lobe and (iv) 30 min after reperfusion. The expression of tumor necrosis factor-α (TNF-α), interleukin (IL)- 1, IL-10 and inducible form of nitric oxide synthase (iNOS) was analysed by western blotting. The expression of mRNA for TNF-α, IL1, IL-10, monocyte chemoattractant protein-1 (MCP-1), nuclear factor kappa beta and iNOS was analysed by reverse transcription–polymerase chain reaction. Caspase-3 activity was determined by enzyme-linked immunosorbent assay. Non-parametric tests were used to compare differences between and within groups. RESULTS: Lung IR markedly increased expression of TNF-α (P = 0.0051) and IL-1 (P = 0.0051) and caspase-3 activity (P = 0.0043) in the CON group compared with the prepneumonectomy levels. A decrease of IL-10 mRNA expression was observed in the CON group after lung reperfusion. In the IP group, TNF-α (P = 0.0011) and IL-1 (P = 0.0001) expression and caspase-3 activity (P < 0.0009) were lower after reperfusion than in the CON group. IP caused reversion of the observed decrease of IL-10 mRNA expression (P = 0.016) induced in liver tissue by lung IR. Lung IR markedly increased the expression of mRNA MCP-1 after 10 min (P = 0.0051) and 30 min (P = 0.0051) of reperfusion. These increases were not observed in the IP or sham groups. CONCLUSIONS: IP prevented liver injury induced by lung IR through the reduction of proinflammatory cytokines and hepatocyte apoptosis.Depto. de BioquĂ­mica y BiologĂ­a MolecularFac. de MedicinaTRUEpu

    Postoperative pulmonary complications; pulmonary and systemic inflammatory responses after lung resection surgery with prolonged one-lung ventilation. Randomized controlled trial comparing intravenous and inhalational anaesthesia

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    Background: Recent studies report the immunomodulatory lung-protective role of halogenated anaesthetics during lung resection surgery (LRS) but have not investigated differences in clinical postoperative pulmonary complications (PPCs). The main goal of the present study was to compare the effect of sevoflurane and propofol on the incidence of PPCs in patients undergoing LRS. The second aim was to compare pulmonary and systemic inflammatory responses to LRS. Methods: Of 180 patients undergoing LRS recruited, data from 174 patients were analysed. Patients were randomized to two groups (propofol or sevoflurane) and were managed otherwise using the same anaesthetic protocol. Bronchoalveolar lavage (BAL) was performed in both lungs before and after one-lung ventilation for analysis of cytokines. Arterial blood was drawn for measurement of the cytokines analysed in the BAL fluid at five time points. Intraoperative haemodynamic and respiratory parameters, PPCs (defined following the ARISCAT study), and mortality during the first month and yr were recorded. Results: More PPCs were detected in the propofol group (28.4% vs 14%, OR 2.44 [95% CI, 1.14-5.26]). First-yr mortality was significantly higher in the propofol group (12.5% vs 2.3%, OR 5.37 [95% CI, 1.23-23.54]). Expression of lung and systemic pro-inflammatory cytokines was greater in the propofol group than in the sevoflurane group. Pulmonary and systemic IL-10 release was less in the propofol group. Conclusions: Our results suggest that administration of sevoflurane during LRS reduces the frequency of the PPCs recorded in our study and attenuates the pulmonary and systemic inflammatory response.Ministerio de SanidadDepto. de FarmacologĂ­a y ToxicologĂ­aFac. de MedicinaTRUEpu

    Modulation of monocyte chemoattractant protein-1 expression by ischaemic preconditioning in a lung autotransplant model

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    Objectives: Monocyte chemoattractant protein-1 (MCP-1) is believed to play a crucial role in lung ischaemia-reperfusion injury (LIRI). Ischaemic preconditioning (IP) has been shown to protect several organs from ischaemia-reperfusion (IR) injury, although less is known about IP's effect on MCP-1 modulation. The objective of this study was to investigate IP's effect on MCP-1 expression in lung tissue and its relationship with oxidative stress and proinflammatory cytokine production in an experimental LIRI model. Methods: Two groups (IP and control groups) of seven large white pigs underwent a lung autotransplant (left pneumonectomy, ex situ superior lobectomy and lower lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two cycles of 5 min of left pulmonary artery occlusion with a 5 min interval of reperfusion between the two occlusions. Blood samples and lung biopsies were obtained at prepneumonectomy (PPn), at prereperfusion (PRp) and up to 30 min after reperfusion of the implanted lobe (Rp-10' and Rp-30'). Haemodynamic and blood-gas measurements, evaluation of oxidative stress in lung tissue and MCP-1, tumour necrosis factor-α (TNF-α) and IL-1 protein and mRNA measurements in lung tissue were performed. Nonparametric tests were used to compare differences between groups. Data are expressed as mean ± SEM. Results: In control lungs, MCP-1 protein levels were found to be higher at PRp, Rp-10' and Rp-30' than at PPn (0.59 ± 0.1 vs. 0.21 ± 0.05, 0.47 ± 0.01 vs. 0.21 ± 0.05 and 0.56 ± 0.01 vs. 0.21 ± 0.05, respectively; P < 0.05). These differences were not evident in the IP group. MCP-1 levels at PRp, Rp-10' and Rp-30' were significantly higher in the control group than in the IP group (0.59 ± 0.1 vs. 0.15 ± 0.02, 0.47 ± 0.01 vs. 0.13 ± 0.01 and 0.56 ± 0.01 vs. 0.27 ± 0.01, respectively; P < 0.05). MCP-1, TNF-α and IL-1 mRNA expressions were lower at PRp, Rp-10' and Rp-30' (control vs. IP group, P < 0.05) when IP was carried out. Lipid peroxidation metabolites and myeloperoxidase activity increase in lung tissue were prevented by IP. Conclusions: In this model, LIRI induced the expression of MCP-1 and the proinflammatory proteins TNF-α and IL-1 in control lungs. IP significantly reduced the expression of these chemokines and cytokines. These features may explain the reduction of oxidative stress observed with IP.Instituto Salud Carlos IIISociedad Española de Neuomologia y Cirugía ToracicaDepto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu
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