The role of oxidative stress in renal injury related to obesity

The mechanisms linking obesity to kidney damage are unknown. AGEs are responsible for renal damage in obese individuals. The receptor AGEs (RAGE) contributes to nuclear transcription factors that result in the production of proinflammatory cytokines and this seems to contribute to the development of renal disease. Thus, intervention with antioxidant can have an important effect in the prevention and treatment of pro-oxidant and pro-inflammatory state in the kidneys resulting from obesity.

Ventilator-induced lung injury and acute respiratory distress syndrome: a basic science review

Acute respiratory distress syndrome is the most severe manifestation of acute lung injury and it is associated with high mortality rate. Despite better understanding of ARDS pathophysiology, its mechanism is still unclear. Mechanical ventilation is the main ARDS supportive treatment. However, mechanical ventilation is a non-physiologic process and complications are associated with its application. Mechanical ventilation may induce lung injury, referred to as ventilator-induced lung injury. Frequently, VILI is related to macroscopic injuries associated with alveolar rupture. The present article is a review of the literature on ventilator-induced lung injury in acute respiratory distress syndrome. Animal and human studies were reviewed. We mainly selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications.

Prone positioning attenuates TNF-alpha production in rabbits with lung injury under protective conventional mechanical ventilation (CMV)

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

HMGB1 in an experimental model of acute lung injury

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

Fatores de risco nutricionais associados à mortalidade em pacientes com lesão renal aguda de acordo com os critérios do Acute Kidney Injury Network (AKIN)

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

MATERIAL MODELING AND ANALYSIS FOR THE DEVELOPMENT OF A REALISTIC BLAST HEADFORM

Blast traumatic brain injury (BTBI) has become an important topic of study because of the increase of such incidents, especially due to the recent growth of improvised explosive devices (IEDs). This thesis discusses a project in which laboratory testing of BTBI was made possible by performing blast loading on experimental models simulating the human head. Three versions of experimental models were prepared – one having a simple geometry and the other two having geometry similar to a human head. For developing the head models, three important parts of the head were considered for material modeling and analysis – the skin, skull and brain. The materials simulating skin, skull and brain went through many testing procedures including dynamic mechanical analysis (DMA). For finding a suitable brain simulant, several materials were tested under low and high frequencies. Step response analysis, rheometry and DMA tests were performed on materials such as water based gels, oil based mixtures and silicone gels cured at different temperatures. The gelatins and silicone gels showed promising results toward their use as brain surrogate materials. Temperature degradation tests were performed on gelatins, indicating the fast degradation of gelatins at room temperature. Silicone gels were much more stable compared to the water based gels. Silicone gels were further processed using a thinner-type additive gel to bring the dynamic modulus values closer to those of human brain matter. The obtained values from DMA were compared to the values for human brain as found in literature. Then a silicone rubber brain mold was prepared to give the brain model accurate geometry. All the components were put together to make the entire head model. A steel mount was prepared to attach the head for testing at the end of the shock tube. Instrumentation was implemented in the head model to obtain effective results for understanding more about the possible mechanisms of BTBI. The final head model was named the Realistic Explosive Dummy Head or the “RED Head.” The RED Head offered potential for realistic experimental testing in blast loading conditions by virtue of its material properties and geometrical accuracy.

Fatores de risco nutricionais associados à mortalidade em pacientes com lesão renal aguda de acordo com os critérios do Acute Kidney Injury Network (AKIN)

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Investigating South American biogeographic history using patterns of skull shape variation on Cerdocyon thous (Mammalia: Canidae)

Patterns of geographic variation of the canid Cerdocyon thous have historically been obscured by its remarkable intraspecific morphological variability. The observed distribution is highly associated with phytophysiognomy, a feature considered highly dynamic along geological time. In the present study, we tested whether vegetation distribution during the Holocene Glacial Maximum of South America (HGM) explains the patterns of morphological variation within Cerdocyon thous. The species was divided in groups according to paleohabitats that could support their presence during the HGM, and then tested for differences in skull morphometrics. The results obtained demonstrate that the climatic changes during the HGM influenced the population structure of this species, resulting in the establishment of geographical groups with different degrees of morphological cohesion. Higher morphological cohesion found in the Northern group might be explained by the marked discontinuity between its geographical range and the rest of the species`distribution. The Eastern and Southern morphological divergence is less striking and, although this could be related to past vegetation distribution, the disappearance of those barriers leads to a population structure that could be slowly breaking down. (C) 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 98, 77-84.

Nitric oxide is responsible for oxidative skin injury and modulation of cell proliferation after 24 hours of UVB exposures

Nitric oxide (NO) is produced by various mammalian cells and plays a variety of regulatory roles in normal physiology and in pathological processes. This article provides evidence regarding the participation of NO in UVB-induced skin lesions and in the modulation of skin cell proliferation following UVB skin irradiation. Hairless mice were subjected to UVB irradiation for 3 hours and the skin evaluated immediately, 6 and 24 hours postirradiation. The skin lipid peroxidation, and NO levels evaluated by chemiluminescence and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunolabelling increased significantly 24 hours after irradiation and decreased under the treatment with aminoguanidine (AG). On the other hand, cell proliferation markers, PCNA and VEGF showed a strong labelling index when AG was used. The data indicate that NO mediates, at least in part, the lipid peroxidation and protein nitration and also promotes the down regulation of factors involved in cell proliferation. This work shows that the NO plays an important role in the oxidative stress damage and on modulation of cell proliferation pathways in UVB irradiated skin.

Effect of simvastatin on passive strain-induced skeletal muscle injury in rats

Introduction: HMG-CoA reductase inhibitors are the most frequently prescribed drugs for treatment of lipid imbalance, but they have side effects, such as myopathy. Our aim was to assess the effect of simvastatin on the inflammatory process induced by skeletal muscle injury. Methods: Rats were divided into experimental groups [control group, simvastatin (20 mg/kg) group, group treated with simvastatin (20 mg/kg) and subjected to injury, and group subjected to injury only]. Histological analysis and analyses of creatine kinase activity and C-reactive protein were performed. Results: Animals treated with simvastatin exhibited significantly greater morphological and structural skeletal muscle damage in comparison to the control group and injured animals without treatment. Conclusions: Although simvastatin has a small anti-inflammatory effect in the early stage after a muscle strain injury, the overall picture is negative, as simvastatin increases the extent of damage to muscle morphology. Further studies are needed. Muscle Nerve 46: 908-913, 2012

Prevention of Intradialytic Hypotension in Patients with Acute Kidney Injury Submitted to Sustained Low-Efficiency Dialysis

Objectives: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). Methods: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0 degrees C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5 degrees C with a variable sodium concentration [150-138 mEq/L] and UF rate. Results: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 +/- 1.25 L vs. 1.59 +/- 1.03 L in control, p = 0.04) when compared with control group. Conclusions: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.

Smart histogram analysis applied to the skull-stripping problem in T1-weighted MRI

In this paper we address the "skull-stripping" problem in 3D MR images. We propose a new method that employs an efficient and unique histogram analysis. A fundamental component of this analysis is an algorithm for partitioning a histogram based on the position of the maximum deviation from a Gaussian fit. In our experiments we use a comprehensive image database, including both synthetic and real MRI. and compare our method with other two well-known methods, namely BSE and BET. For all datasets we achieved superior results. Our method is also highly independent of parameter tuning and very robust across considerable variations of noise ratio.

Antioxidant treatment protects against matrix metalloproteinase activation and cardiomyocyte injury during acute pulmonary thromboembolism

Increased reactive oxygen species (ROS) promote matrix metalloproteinase (MMP) activities and may underlie cardiomyocyte injury and the degradation of cardiac troponin I (cTI) during acute pulmonary thromboembolism (APT). We examined whether pretreatment or therapy with tempol (a ROS scavenger) prevents MMP activation and cardiomyocyte injury of APT. Anesthetized sheep received tempol infusion (1.0 mg kg(-1) min(-1), i.v.) or saline starting 30 min before or 30 min after APT (autologous blood clots). Control animals received saline. Hemodynamic measurements were performed. MMPs were studied in the right ventricle (RV) by gelatin zymography, fluorimetric activity assay, and in situ zymography. The ROS levels were determined in the RV and cTI were measured in serum samples. APT increased the pulmonary arterial pressure and pulmonary vascular resistance by 146 and 164 %, respectively. Pretreatment or therapy with tempol attenuated these increases. While APT increased RV + dP/dt (max), tempol infusions had no effects. APT increased RV MMP-9 (but not MMP-2) levels. In line with these findings, APT increased RV MMP activities, and this finding was confirmed by in situ zymography. APT increased the RV ROS levels and tempol infusion, before or after APT, and blunted APT-induced increases in MMP-9 levels, MMP activities, in situ MMP activities, and ROS levels in the RV. cTI concentrations increased after APT, and tempol attenuated these increases. RV oxidative stress after APT increases the RV MMP activities, leading to the degradation of sarcomeric proteins, including cTI. Antioxidant treatment may prevent MMP activation and protect against cardiomyocyte injury after APT.