A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury

Ischemic-reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin-3 is a multi-functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro-inflammatory cytokines. The aim of this study was evaluate the role of galectin-3 in the inflammation triggered by IRI. Galectin-3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP-1, IL-6 and IL-1 beta were studied by real-time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 +/- 85.21 mg/dl vs. gal-3 KO = 123.74 +/- 29.64 mg/dl, P = 0.001). Galectin-3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP-1, IL-6, IL-1 beta, less macrophage infiltration and lower ROS production at early time points. Galectin-3 seems to play a role in renal IRI involving the secretion of macrophage-related chemokine, pro-inflammatory cytokines and ROS production.

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720

Ischemia and reperfusion injury (IR) is an antigen independent inflammatory process that causes tissue damage. After IR, kidneys up-regulate leukocyte adhesion molecules and toll-like receptors (TLRs). Moreover, injured kidneys can also secrete factors (i.e. heat shock protein) which bind to TLRs and trigger intracellular events culminating with the increase in the gene expression of inflammatory cytokines. FTY720 is an immunomodulatory compound and protects at least in part kidneys submitted to IR. The mechanisms associated with FTY720`s beneficial effects on kidneys after IR remain elusive. We investigated whether FTY720 administration in mice submitted to kidney IR is associated with modulation of TLR2 and TLR4 expression. C57BL/6 mice submitted to 30 min of renal pedicles clamp were evaluated for serum parameters (creatinine, urea and nitric oxide), kidney histology, spleen and kidney infiltrating cells expression of TLR2 and TLR4, resident kidney cells expression of TLR2 and TLR4 and IL-6 protein expression in kidney. FTY720-treated mice presented decrease in serum creatinine, urea and nitric oxide, diminished expression of TLR2 and TLR4 both in spleen and kidney infiltrating cells, and reduced kidney IL-6 protein expression in comparison with IR non-treated mice. However, acute tubular necrosis was present both in IR non-treated and IR + FTY720-treated groups. Also, FTY720 did not prevent TLR2 and TLR4 expression in kidney resident cells. In conclusion, FTY720 can promote kidney function recovery after IR by reducing the inflammatory process. Further studies are needed in order to establish whether TLR2 and TLR4 down regulation should be therapeutically addressed as protective targets of renal function and structure after IR. (C) 2011 Elsevier B.V. All rights reserved.

Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B(1) receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. (C) 2010 Elsevier B.V. All rights reserved.

Effect of sildenafil in renal ischemia/reperfusion injury in rats

To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R), by scintigraphy and histopathological evaluation in rats. Methods: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial) renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12) received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12). Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. Results: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (p<0.05). Sildenafil treatment resulted in better differential function of the left kidneys 24h after reperfusion, compared with controls. Histopathologically, the left kidney of control rats (24 hours after I/R) showed a higher degree of cellular necrosis when compared with the sildenafil treated rats (p<0.05). Conclusion: Sildenafil had a protective effect in rat kidneys subjected to normothermic I/R, demonstrated by scintigraphy and histomorphometry

Second generation European corn borer injury and Irish potato physiology, yield, and quality

European corn borer (ECB) [Ostrinia nubilalis (Hubner)] (Lepidoptera: Crambidae) is known to infest Irish potato (Solanum tuberosum L.) but only causes economic damage during the first generation in East Coast potato producing areas. However, in Nebraska, second generation ECB infest potato plants during the bulking period and may reduce yield and/or potato quality. Experiments were conducted in 2001, 2002, and 2003 to examine physiological and yield effects of second generation ECB injury to potato in Nebraska. Pike, Atlantic, and three Frito Lay proprietary varieties (FL1867, FL1879, and FL1833) were used. Experimental plots were infested with four ECB egg masses per plant to simulate ECB infestation by second-generation larvae; controls received no egg masses. Photosynthetic rates, tuber weights, tuber size grades, solids, and fry quality were measured. Potato plants with ECB infestation had significantly reduced photosynthetic rates on ECB-infested stems and on uninfested stems on the same plant when larvae were in the fifth instar. When insects were in the fourth instar, photosynthetic rates were reduced only on ECB-infested stems. In 2001, ECB infestation reduced the average mass of large tubers and increased the amount of small tubers in FL1867 and FL1879. In 2002, significant yield reductions were not observed. Across both years, ECB-infested plots produced fewer large (65- to 100-mm diam.) tubers than control plots. Other tuber properties and chip qualities were unaffected. This study indicates that second generation ECB infestation of approximately 30% infested plants results in economic loss for some chipping varieties and affects tuber bulking. In contrast to east coast growers, Midwest potato farmers must be concerned with second generation ECB.

Influence of Mahanarva fimbriolata (Stål) (Hemiptera: Cercopidae) injury on the quality of cane juice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

High laryngeal mask airway pressures resulting from nitrous oxide do not increase pharyngeal mucosal injury in dogs

Purpose: During general anesthesia, nitrous oxide (N2O) diffuses rapidly into the air-filled laryngeal mask airway (LMA) cuff, increasing intracuff pressure. There is no clear correlation between LMA intracuff pressure and pressure on the pharynx. We have studied the effects of high LMA intracuff pressures secondary to N2O on the pharyngeal mucosa of dogs.Methods: Sixteen mongrel dogs were randomly allocated to two groups: G1 (intracuff volume, 30 mL; n = 8) breathed a mixture of O-2 (1 L.min(-1)) and air (1 L.min(-1)) and G2 (intracuff volume, 30 mL; n=8) a mixture of O-2 (1 L.min(-1)) and N2O (1 L.min(-1)). Anesthesia was induced and maintained with pentobarbitone. LMA cuff pressure was measured at zero (control), 30, 60, 90 and 120 min after #4 LMA insertion. The dogs were sacrificed, and biopsy specimens from seven predetermined areas of the pharynx in contact with the LMA cuff were collected for light (LM) and scanning electron microscopic (SEM) examination by a blinded observer.Results: LMA intracuff pressure decreased with time in G1 (P < 0.001) and increased in G2 (P < 0.001). There was a significant difference between the groups (P < 0.001). In both groups, the LM study showed a normal epithelium covering the pharyngeal mucosa and mild congestion in the subepithelial layer There were no differences between the groups (P > 0.10) or among the areas sampled (P > 0.05). In both groups, the SEM study showed a normal pharyngeal mucosa with mild superficial desquamation. Few specimens in G1 and G2 showed more intense epithelial desquamation.Conclusion: High LMA intracuff pressures produced by N2O do not increase pharyngeal mucosal injury in dogs.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Remifentanil, Isoflurane, and Preconditioning Attenuate Renal Ischemia/Reperfusion Injury in Rats

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

Enzyme Biomarkers of Renal Tubular Injury in Arterial Surgery Patients

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

Lung ultrasound in acute respiratory distress syndrome and acute lung injury

Purpose of reviewLung ultrasound at the bedside can provide accurate information on lung status in critically ill patients with acute respiratory distress syndrome.Recent findingsLung ultrasound can replace bedside chest radiography and lung computed tomography for assessment of pleural effusion, pneumothorax, alveolar- interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/de-recruitment. It can also accurately determine the type of lung morphology at the bedside (focal or diffuse aeration loss), and therefore it is useful for optimizing positive end-expiratory pressure. The learning curve is brief, so most intensive care physicians will be able to use it after a few weeks of training.SummaryLung ultrasound is noninvasive, easily repeatable and allows assessment of changes in lung aeration induced by the various therapies. It is among the most promising bedside techniques for monitoring patients with acute respiratory distress syndrome.

Erythropoietin Attenuates Apoptosis After Ischemia-Reperfusion-Induced Renal Injury in Transiently Hyperglycemic Wister Rats

Background. Hyperglycemia is associated with a decreased tolerance to ischemia and an increased severity of renal ischemia reperfusion (I/R) injury. It has been suggested that erythropoietin (EPO) attenuates this effect in normoglycemic animals. This study sought to examine the effects of EPO on treatment renal I/R injury (IRI) in transiently hyperglycemic rats.Material and Methods. Twenty-eight male Wister rats anesthetized with isoflurane received glucose (2.5 g.kg(-1) intraperitoneally) before right nephrectomy. They were randomly assigned to four groups: sham operation (S); IRI (ISO); IRI+EPO, (600 UI kg(-1) low-dose EPO [EL]); and IRI+EPO 5000 UI kg(-1) (high-dose EPO [EH]). IRI was induced by a 25-minute period of left renal ischemia followed by reperfusion for 24 hours. Serum Creatinine and glucose levels were measure at baseline (M1), immediately after the ischemic period (M2), and at 24 hours after reperfusion (M3). After sacrificing the animals, left kidney specimens were submitted for histological analysis including flow cytometry to estimate tubular necrosis and the percentages of apoptotic, dead or intact cells.Results. Scr in the ISO group was significantly higher at M3 than among the other groups. Percentages of early apoptotic cells in ISO group were significantly higher than the other groups. Percentages of late apoptotic cells in S and ISO groups were significantly greater than EL and EH groups. However, no significant intergroup differences were observed regarding the incidence of tubular necrosis.Conclusions. Our results suggested that, although not preventing the occurrence of tubular necrosis, EPO attenuated apoptosis and glomerular functional impairment among transiently hyperglycemic rats undergoing an ischemia/reperfusion insult.

Fibular Nerve Injury After Small Saphenous Vein Surgery

Superficial nerve injuries are very common during varicose vein surgery. In contrast, deep nerve injuries are rare and reported especially when surgery involves the small saphenous vein (SSV). The deep motor nerves most commonly injured are the tibial nerve and the peroneal nerve, which are directly or indirectly affected by extrinsic compression, stretching, or healing process involvement. In this report, two cases of common fibular nerve injury after SSV stripping are described, including treatment used and patient outcomes. Nerve damage mechanisms, anatomy, and prevention strategies are also discussed. In conclusion, fibular nerve damage may occur during SSV stripping. Preventive measures include careful preoperative ultrasonographic investigation of the anatomy of the vein, determining location of the saphenopopliteal joint, and careful dissection far from fibular nerve and restricted to the popliteal fossa.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUÇÃO: A decisão de quando iniciar a diálise em pacientes com lesão renal aguda (LRA) que apresentam síndrome urêmica está bem estabelecida, entretanto, com ureia < 200 mg/dl o melhor momento para iniciar a diálise torna-se incerto. OBJETIVO: Este estudo teve como objetivo avaliar a mortalidade e a recuperação da função renal em pacientes com LRA, cujo início da diálise ocorreu em diferentes níveis de ureia. MÉTODOS: Estudo retrospectivo desenvolvido em hospital escola, no estado de São Paulo, Brasil, envolvendo 86 pacientes submetidos à diálise. RESULTADOS: A diálise foi iniciada com uréia > 150 mg/dl em 23 pacientes (grupo I) e uréia > 150 mg/dl em 63 pacientes (grupo II). Hipervolemia e mortalidade foram mais frequentes no grupo I que no grupo II (65,2 x 14,2% - p < 0,05; 39,1 x 68,9% - p < 0,05, respectivamente). Entre os sobreviventes, a recuperação renal foi maior no grupo I (71,4 e 36,8%, respectivamente, p < 0,05). A análise multivariada mostrou risco independente de mortalidade relacionado à sepse, idade > 60 anos, diálise peritoneal e uréia > 150 mg/dl no início da diálise. CONCLUSÃO: Menor mortalidade e maior recuperação renal estão associadas com o diálise iniciada precocemente, conforme baixos níveis de ureia, em pacientes com LRA.

Can Delivery Dialysis Dose Affect Survival of Acute Kidney Injury Patients?

Intensity of dialysis dose in acute kidney injury (AKI) might benefit critically ill patients. The aim of this study was to evaluate the effect of intermittent hemodialysis (IHD) dose on mortality in patients with AKI. Methods: Prospective observational study was performed on AKI patients treated with IHD. The delivered dialysis dose per session was calculated based on single-pool Kt/V urea. Patients were allocated in two groups according to the weekly delivered median Kt/V: higher intensity dialysis dose (HID: Kt/V higher than median) and lower intensity dialysis dose (LID: Kt/V lower than median). Thereafter, AKI patients were divided according to the presence or absence of sepsis and urine output. Clinical and lab characteristics and survival of AKI patients were compared. Results: A total of 121 AKI patients were evaluated. Forty-two patients did not present with sepsis and 45 did not present with oliguria. Mortality rate after 30 days was lower in the HID group without sepsis (14.3% x 47.6%; p = 0.045) and without oliguria (31.8% x 69.5%; p = 0.025). Survival curves also showed that the HID group had higher survival rate when compared with the LID group in non-septic and non-oliguric patients (p = 0.007 and p = 0.003, respectively). Conclusion: Higher dialysis doses can be associated with better survival of less seriously ill AKI patients.