N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation

Campos R, Shimizu MH, Volpini RA, de Bragan a AC, Andrade L, Lopes FD, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 302: L640-L650, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00097.2011.-Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the alpha-subunit of the epithelial sodium channel (alpha-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, alpha-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

Purpose: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. Methods: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. Results: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001) but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean +/- standard deviation baseline central macular thickness (552 +/- 150 mu m) reduced significantly one month (322 +/- 127 mu m, P=0.0001) and three months (439 perpendicular to 179 mu m, P=0.01) after treatment. Conclusions: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

INTRAVITREAL INJECTION OF RANIBIZUMAB DURING CATARACT SURGERY IN PATIENTS WITH DIABETIC MACULAR EDEMA

Purpose: To investigate macular thickness and visual acuity changes after 1 intravitreal injection of 0.5-mg ranibizumab during phacoemulsification cataract surgery in eyes with diabetic macular edema refractory to laser treatment. Methods: Eleven eyes of 11 patients with diabetic macular edema refractory to modified Early Treatment Diabetic Retinopathy Study laser therapy received intravitreal during phacoemulsification cataract surgery. Comprehensive ophthalmic evaluation was performed preoperatively and at 1, 4, 8 +/- 1, and 12 +/- 2 weeks postoperatively. Main outcome measures included central subfield thickness and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity. Results: Eleven patients completed the 12-week study visit. Mean central subfield thickness (+/- SEM) was 399.82 +/- 29.50 mu m at baseline and did not change significantly at any postoperative study visit (P > 0.05). Mean (+/- SEM) best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was 0.95 +/- 0.13 logarithm of the minimum angle of resolution (20/200) at baseline and was significantly improved at Weeks 1 (0.38 +/- 0.13), 4 (0.38 +/- 0.11), 8 (0.35 +/- 0.08), and 12 (0.46 +/- 0.12) after treatment (P < 0.05). Conclusion: In this case series of patients with diabetic macular edema refractory to laser therapy, intravitreal ranibizumab administered during cataract surgery was associated with no significant change in central subfield thickness postoperatively. Significant improvement in best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was observed after treatment, likely because of cataract removal. RETINA 32:1799-1803, 2012

Compression stockings have a synergistic effect with walking in the late afternoon to reduce edema of the lower limbs

Aim. The aim of this study was to evaluate whether an association of elastic stockings and walking for a short period in the late afternoon reduces leg edema. Methods. Volume changes of the legs of sixteen patients (32 limbs), who walked on a treadmill for 30 minutes using elastic compression stockings, were analyzed in a quantitative, cross-over randomized (in order of arrival at the clinic) study. They were submitted to volumetry using the water displacement technique and subsequently required to put on 20/30 made-to-measure compression stockings (Sigvaris). The patients walked on a treadmill for 30 minutes and after removing the stockings volumetry of the legs was again performed. Legs were assessed using the CEAP classification and divided into groups. Analysis of variance was used for statistical analysis with an alpha error of 5% being considered acceptable. Results. When participants walked wearing compression stockings, there was a reduction in leg volume. When the CEAP classification was evaluated, it was noted that there was a statistically significant difference for the CEAP C0, C1 and C2 categories of legs using stockings compared to those that did not use. Conclusion. Compression stockings have a synergistic effect with walking in the late afternoon thus reducing edema of the lower limbs. [Int Angiol 2012;31:490-3]

Manifestação rara de edema agudo de pulmão associado à miocardite lúpica aguda

O lupus eritematoso sistêmico (LES) é a mais comum das doenças auto-imunes sistêmicas, ocorrendo com maior freqüência no sexo feminino, usualmente na faixa etária entre 16 e 55 anos1,2. Embora os rins classicamente sejam os órgãos mais acometidos no LES, o coração e a circulação cardiopulmonar também podem ser afetados de forma significativa3. Nesse contexto, a ocorrência de edema agudo de pulmão associado à miocardite lúpica é rara e de tratamento imunossupressor específico ainda incerto.

Pro-inflammatory effects of the aqueous extract of Echinometra lucunter sea urchin spines

The sea urchin, Echinometra lucunter, can be found along the Western Central Atlantic shores. In Brazil, it is responsible by circa 50% of the accidents caused by marine animals. The symptoms usually surpass trauma and may be pathologically varied and last differently, ranging from spontaneous healing in a few days, to painful consequences lasting for weeks. In this work, we have mimicked the sea urchin accident by administering an aqueous extract of the spine into mice and rats and evaluated the pathophysiological developments. Our data clearly indicate that the sea urchin accident is indeed a pro-inflammatory event, triggered by toxins present in the spine that can cause edema and alteration in the leukocyte-endothelial interaction. Moreover, the spine extract was shown to exhibit a hyperalgesic effect. The extract is rich in proteins, as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but also contains other molecules that can be analyzed by reversed phase high-performance liquid chromatography. Altogether, these effects corroborate that an E. lucunter encounter is an accident and not an incident, as frequently reported by the victims.

Lufaxin, a Novel Factor Xa Inhibitor From the Salivary Gland of the Sand Fly Lutzomyia longipalpis Blocks Protease-Activated Receptor 2 Activation and Inhibits Inflammation and Thrombosis In Vivo

Objective-Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. Methods and Results-Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant approximate to 3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl3-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. Conclusion-Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events. (Arterioscler Thromb Vasc Biol. 2012;32:2185-2196.)

Vitreous Pharmacokinetics and Retinal Safety of Intravitreal Preserved Versus Non-preserved Triamcinolone Acetonide in Rabbit Eyes

Purpose: To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina. Methods: A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4 mg/0.1ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4 mg/0.1ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy. Results: Median intravitreal concentrations of TA-BA (mu g/ml) were 1903.1, 1213.0, 857.8, 442.0, 248.6 at 3, 7, 14, 21 and 28 days after injection. Intravitreal concentrations of TA-PF (mu g/ml) were 1032.9, 570.1, 516.6, 347.9, 102.8 at 3, 7, 14, 21 and 28 days after injection. The median intravitreal triamcinolone concentration was significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection (p < 0.05). There was no significant difference between the two groups in median triamcinolone concentration at the other time points evaluated. There was no evidence of toxic effects on the retina in either group based on ERG or histological analyses. Conclusions: Following a single intravitreal injection, the median concentration of triamcinolone acetonide is significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection. No toxic reactions in the retina were observed in either group.

Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients

BACKGROUND: Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. OBJECTIVE: To assess the efficacy of a therapy and its cosmetic results. METHODS: In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. RESULTS: The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). CONCLUSION: PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system

OBJECTIVE: This study evaluated the performance of lungs that were preserved with different solutions (Celsior, Perfadex or saline) in an ex vivo rat lung perfusion system. METHODS: Sixty Wistar rats were anesthetized, anticoagulated and randomized into three groups (n = 20). The rats were subjected to antegrade perfusion via the pulmonary artery with Perfadex, Celsior, or saline, followed by 6 or 12 hours of ischemia (4 degrees C, n = 10 in each group). Respiratory mechanics, gas exchange and hemodynamics were measured at 10-minute intervals during the reperfusion of heart-lung blocks in an ex vivo system (IL2-Isolated Perfused Rat or Guinea Pig Lung System, Harvard Apparatus, Holliston, Massachusetts, USA; Hugo Sachs Elektronik, Germany) for 60 minutes. The lungs were prepared for histopathology and evaluated for edema following reperfusion. Group comparisons were performed using ANOVA and the Kruskal-Wallis test with a 5% level of significance. RESULTS: Gas exchange was not significantly different between lungs perfused with either Perfadex or Celsior at the same ischemic times, but it was very low in lungs that were preserved with saline. Airway resistance was greater in the lungs that were preserved for 12 hours. Celsior lungs that were preserved for 6 and 12 hours exhibited lower airway resistance (p = 0.01) compared to Perfadex lungs. Pulmonary artery pressure was not different between the groups, and no significant differences in histopathology and apoptosis were observed between the groups. CONCLUSIONS: Lungs that were preserved with Celsior or Perfadex exhibited similar gas exchange and histopathological findings. Airway resistance was slightly lower in the Celsior-preserved lungs compared with the Perfadex-preserved lungs.

Electroretinographic findings associated with panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab treatment for high-risk proliferative diabetic retinopathy

To evaluate changes in electroretinographic (ERG) findings after panretinal photocoagulation (PRP) compared to PRP plus intravitreal injection of ranibizumab (IVR) in eyes with high-risk proliferative diabetic retinopathy (PDR). Patients with high-risk PDR and no prior laser treatment were assigned randomly to receive PRP (PRP group; n = 9) or PRP plus IVR (PRPplus group; n = 11). PRP was administered in two sessions (weeks 0 and 2), and IVR was administered at the end of the first laser session (week 0) in the PRPplus group. Standardized ophthalmic evaluations including (ETDRS) best-corrected visual acuity (BCVA), and fluorescein angiography to measure area of fluorescein leakage (FLA), were performed at baseline and at weeks 16 (+/- 2), 32 (+/- 2) and 48 (+/- 2). ERG was measured according to ISCEV standards at baseline and at week 48 (+/- 2). At 48 weeks, 2,400-3,000 laser spots had been placed in eyes in the PRP group, while only 1,400-1,800 spots had been placed in the PRPplus group. Compared to baseline, there was a statistically significant (P < 0.05) FLA reduction observed at all study visits in both groups, with the reduction observed in the PRPplus group significantly larger than that in the PRP group at week 48. ROD b-wave amplitude was significantly reduced to 46 +/- A 5 % (P < 0.05) of baseline in the PRP group and 64 +/- A 6 % (P < 0.05) in the PRPplus group. This reduction was significantly larger in the PRP group than in the PRPplus group (P = 0.024; t Test). Similar results were observed for the dark-adapted Combined Response (CR) b-wave amplitude, with a reduction at 48 weeks compared to baseline of 45 +/- A 4 % in the PRP group and 62 +/- A 5 % in the PRPplus group; the reduction in CR b-wave amplitude was significantly larger in the PRP group than in the PRPplus group (P = 0.0094). CR a-wave, oscillatory potentials, cone single flash, and 30 Hz flicker responses showed statistically significant within-group reductions, but no differences in between-group analyses. These results suggest that treating high-risk PDR with PRP plus IVR is effective for PDR control, and permits the use of less extensive PRP which, in turn, induces less retinal functional loss, in particular for rod-driven post-receptoral responses, than treatment with PRP alone.

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects

The development of the percutaneous muscle biopsy technique is recognized as one of the most important scientific contributions in advancing our understanding of skeletal muscle physiology. However, a concern that this procedure may be associated with adverse events still exists. We reported the incidence of adverse outcomes associated with percutaneous muscle biopsy in healthy and diseased subjects. Medical records of 274 volunteers (496 muscle biopsies) were reviewed. This included 168 healthy subjects (330 muscle biopsies) as well as 106 chronically ill patients (166 muscle biopsies). This latter group encompassed patients with type II diabetes (n=28), osteoarthritis (n=39), inclusion body myositis (n=4), polymyositis (n=4), and chronic heart failure (n=31). The most common occurrences were pain (1.27%), erythema (1.27%), and ecchymosis (1.27%). Panic episode, bleeding, and edema were also reported (0.21%, 0.42%, and 0.84%, respectively), while infection, hematoma, inflammation, denervation, numbness, atrophy, and abnormal scarring were not verified. The percent of incidents did not differ between healthy and ill individuals. In conclusion, the incidence of complications associated with percutaneous muscle biopsy is scarce and of minor clinical relevance. Additionally, the rate of adverse events is comparable between healthy and chronically ill subjects.

Evaluation of tissue reaction to Aroeira (Myracrodruon urundeuva) extracts: a histologic and edemogenic study

Objectives: This study evaluated subcutaneous tissue response to Aroeira (Myracrodruon urundeuva) extract employing edemogenic and histological analyses. Material and methods: Test groups consisted of aqueous and ethanolic Aroeira extracts and saline (control). For groups consisted of aqueous and ethanolic Aroeira extracts and saline Blue. After 30 min, the extracts and saline were injected on the dorsum of the rats, which were then sacrificed after 3 and 6 h. Readings were performed in a spectrophotometer. For subcutaneous implantation, 30 rats received a polyethylene tube containing the extracts on their dorsum and then they were killed after 7 and 28 days. The samples were processed for histological analysis and evaluated with a light microscope. The inflammatory infiltrate was quantified. Results: There were no statistically significant differences between aqueous extract and saline groups in relation to edema quantification in the different periods (p > 0.05). Ethanolic solution resulted in more edema independently of the experimental period (p < 0.05). Histological analysis showed similar results on the 7-day period for the 3 groups. There was a notable reduction on inflammatory cell number for saline and aqueous extract groups at 28 days. Conclusion: The aqueous extract showed biocompatible properties similar to those of saline.

Jatropha curcas pericarp toxicity in sheep

Physic nut (Jatropha curcas) is a plant cultivated for biofuel production. Pericarp is a potential livestock food source by-product. However, its use may be limited due to the presence of toxic compounds, mainly phorbol esters. Thus, this study aimed to evaluate pericarp toxicity. Twenty sheep were divided in four groups, one control group which did not receive the plant and three experimental groups which received pericarp in 15% (G15), 30% (G30) and 45% (G45) concentrations for 23 days. After 10 days of treatment, pericarp ingestion produced food intake decrease, diarrhea, dehydration and loss of body condition. All treated groups showed decrease in alkaline phosphatase activity. G30 animals presented reductions in urea and total protein concentrations, and increase in potassium and sodium levels. G45 animals showed increase in serum aspartate aminotransferase activity and in albumin, creatinin, total and indirect bilirubin levels. Anatomohistopathologic findings included ascites, hydropericardium, congestion of the gastintestinal tract and lungs, pulmonary edema and adhesions in the thoracic cavity, renal tubular cells and centrilobular cytoplasmic vacuolation and lymphohistiocytic pneumonia and lymphoplasmacytic and histiocytic enteritis. On the physiochemical analysis 0.3845mg of phorbol esters/g of pericarp were detected. It is concluded that J. curcas pericarp is toxic and is not recommended for sheep feeding.

Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration-induced Lung Injury

Background: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.