Edema Index Research Articles

Abstract 12648: Deletion of 12/15 Lipoxygenase Improves Left Ventricle Function and Survival by Resolving Inflammation Post Myocardial Infarction

12/15 lipoxygenase (LOX) is crucial in the inflammatory process leading to diabetes and atherosclerosis. However, the role of 12/15 LOX in myocardial infarction (MI) and left ventricle (LV) remodeling is unclear. We assessed the role of 12/15 LOX in resolving inflammation in post-MI LV remodeling. 8-12 weeks old C57BL/6J wild-type (WT; n=67) and 12/15 LOX (LOX –/– ; n=78) male mice were subjected to permanent coronary artery ligation surgery and monitored through day (d)1 and d5. No MI surgery mice were maintained as d0 naïve controls. LOX -/- mice showed higher survival rate, improved fractional shortening with reduced remodeling and edema index than WT at d1 and d5 post-MI (all p<0.05). LOX -/- mice showed increased Cxcl5 expression at d1 post-MI, consistent with stimulated neutrophil recruitment in the infarct region that was decreased at d5 compared to WT. LOX -/- mice infarct had increased expression of Ccl2 and Cxcl1, that stimulated an earlier recruitment of monocytes with increased macrophages population at d5 (all p<0.05) compared to WT. The altered kinetics of immune cells post-MI indicates a rapid resolving phase, through increase in alternative macrophage phenotypes with reduced collagen density in LOX -/- mice compared to WT mice at d5 post-MI. LOX -/- mice showed a coordinated COX-1 and COX-2 response at d1 post MI, leading to an evident increase in 5-LOX and hemoxygenase-1 (HO-1) at d5 post-MI. 12/15 LOX deletion enhanced the recruitment of alternative macrophages with secretion of HO-1 to resolve inflammation. In-vitro addition of LOX metabolite 12 hydroxyeicosatetraenoic acid to LOX -/- fibroblast induced early expression of COX-2 and 5-LOX compared to WT, indicating 5LOX role in resolution of inflammation. Post-MI increased expression of TIMP-1 and decrease in MMP-9 at d1 and α-SMA at d5 in LOX -/- mice suggested controlled differentiation of fibroblast-to-myofibroblast which is key event during ventricular tissue repair and resolving phase. This change is supported by increased expression of tgf-βi, ctgf and admats-2 (all P<0.05) at d5 post MI. In conclusion, absence of 12/15 LOX improves post-MI survival rates and attenuates LV dysfunction by resolving inflammation through coordination of 5-LOX and HO-1 as key inflammation resolving enzymes.

Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells

This study aims to determine if erythromycin has neuroprotective effects against transient ischemia and oxygen-glucose deprivation (OGD) in cultured neuronal cells. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90min, followed by reperfusion. The animals received a subcutaneous single injection of erythromycin lactobionate (EM, 50mg/kg) or vehicle immediately after ischemia. Infarct volume, edema index, and neurological performance were evaluated at 24 and 72h after reperfusion. Immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) were conducted in the cortex at 24h. Primary cortical neuronal cell cultures were prepared from the cerebral cortices of the animals and then subjected to OGD for 3h. Ten or 100μM EM was added before OGD to determine the effect of EM on cell viability after OGD. EM significantly reduced infarct volume (p<0.01) and edema volume (p<0.05) and improved neurological deficit scores (p<0.05) at 24 and 72h. EM significantly suppressed the accumulation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) and markedly reduced Iba-1 (p<0.01) and TNF-α expression (p<0.01). Treatment with 100M EM in vitro significantly reduced cell death after OGD. EM reduces neuronal damage following cerebral ischemia and OGD and may have antioxidant and anti-inflammatory effects.

Clinical Scenario is Well Correlated with Systemic Edema Index by Bio-impedance Analysis Only If Classified Appropriately

Clinical Scenario (CS) in acute decongestive heart failure (ADHF) is categorized by both initial systolic blood pressure (SBP) and clinical condition. Edema index (EI) is recently advocated heart failure management index measured by bio-impedance analysis. The aim is to compare the difference of EI in CS groups (CS1-5) classified by SBP only and SBP with clinical condition.

Exercise Pretreatment Promotes Mitochondrial Dynamic Protein OPA1 Expression after Cerebral Ischemia in Rats

Exercise training is a neuroprotective strategy in cerebral ischemic injury, but the underlying mechanisms are not yet clear. In the present study, we investigated the effects of treadmill exercise pretreatment on the expression of mitochondrial dynamic proteins. We examined the expression of OPA1/DLP1/MFF/Mfn1/Mfn2, which regulatesmitochondrial fusion and fission, and cytochrome C oxidase subunits (COX subunits), which regulatemitochondrial functions, after middle cerebral artery occlusion (MCAO) in rats. T2-weighted magnetic resonance imaging (MRI) was evaluated as indices of brain edema after ischemia as well. Treadmill training pretreatment increased the expression levels of OPA1 and COXII/III/IV and alleviated brain edema, indicating that exercise pretreatment provided neuroprotection in cerebral ischemic injury via the regulation of mitochondrial dynamics and functions.

3D Blood Pressure Pulse Analyzer로 측정한 맥파 에너지와 산후 부종과의 상관성 연구

Purpose: This study was performed to find correlations between Edema Index and Pulse Energy in early postpartum period. Methods: Fiftynine postpartum women were participated in this study which was conducted with Inbody 720 (Biospace Co. Ltd) and 3D Blood Pressure Pulse Analyzer (3D-MAC). Edema Index (Extra Cellular Water/Total Body Water) calculated after body composition analysis and 3D-MAC result (Pulse Energy) were analysed within a week after delivery. Results: The results were as follows 1. Edema Indexes of the upper, lower limbs, trunk and whole body were associated with each other respectively. 2. Edema Indexes and Right Kwan pulse energy had significant positive correlation. 3. Right Kwan pulse energy showed positive correlations with Left Kwan, Right Chon, Right Cheok. Conclusions: Viscera associated with Postpartum Edema are Spleen, Lung, Liver and Vital Gate. The most important thing is thought to be Spleen.

Preliminary clinical study of recombinant human endostatin combined with radiotherapy in the treatment of brain metastases of non-small cell lung cancer and the patients suitable for this therapy

Objective To investigate the therapeutic effects of recombinant human endostatin (RHES) combined with radiotherapy on brain metastases (BM) of non-small cell lung cancer (NSCLC) and the patients suitable for this therapy. Methods Eighty patients with BM of NSCLC were randomly divided into RHES combined with radiotherapy group (combination group) and radiotherapy alone group (each group with 40 patients). The short-term effective rate, overall survival time, cerebral edema index and adverse reactions were observed and the expressions of vascular endothelial growth factor receptor 2 (VEGFR2) protein in primary lesions were detected with immunohistochemical method in all patients. Results Compared with radiotherapy alone group, brain edema was significantly relieved (t=4.9, P=0.000) and there were no marked adverse reactions in combination group. In short-term effective rate, there was no statistical significance in total population (n=80, 90% vs. 75%, χ2=3.11, P=0.07), but there was statistical significance in the patients with positive VEGFR2 (93% vs. 67.7%, χ2=6.31, P=0.012). In overall survival time, there was no statistical significance in total population (n=80, P=0.35, 95% CI: 0.25-1.30) or in the patients with positive VEGFR2 (P=0.109, 95% CI: 0.40-1.34). Conclusion Compared with radiotherapy alone, RHES combined with radiotherapy can relieve brain edema in the patients with BM of NSCLC and obtain better short-term effective rate in the patients with positive VEGFR2. Key words: Recombinant human endostatin; Radiotherapy; Vascular endothelial growth factor receptor 2; Lung cancer; Brain metastases

Abstract W MP94: Acute Inflammation Expands Cerebral Microbleeds in a Mouse Model of Cerebral Amyloid Angiopathy

Introduction: Cerebral microscopic hemorrhages are the pathologic substrate of cerebral microbleeds (CMB). Little is known about mechanisms of expansion of CMB. Here we studied the dynamics of CMB after acute inflammation, using a transgenic mouse model of cerebral amyloid angiopathy with spontaneous microscopic hemorrhages and endotoxin (lipopolysaccharide, LPS) as an inflammatory stimulus. Methods: 21-month old Tg2576 mice and wildtype littermates received a single dose of LPS, 100 or 1000 ug/kg i.p., or phosphate-buffered saline (PBS) as control. Mice were sacrificed 48 hours later and brains were collected for the analysis of microscopic hemorrhages, as well as edema formation, blood-brain barrier constituents and glial activation. Differences among groups were tested by anova and contrasts. Results: Hematoxylin and eosin staining demonstrated no freshly-formed microscopic hemorrhages in LPS-treated mice. Using Prussian blue staining, we found that total area, average size, and number of CMB differed significantly between PBS-treated wildtype and transgenic mice (p=0.03, p=.04 and p=.03 respectively). Acute inflammation did not significantly affect total area, average size, or number of CMB in wildtype animals. For transgenic mice, both doses of LPS significantly (p&lt;.01) increased the total area of Prussian blue-positive lesions (2.2 to 2.9-fold increase), and higher LPS dose significantly (p&lt;.01) increased average size of CMB by 2.6-fold; both average and total size of CMB increased in a dose-dependent manner. IgG and fibrinogen levels significantly increased after high dose LPS injection in both wildtype and transgenic mice (p&lt;.05). Tight junction protein claudin-5 levels were also increased in high dose LPS-treated mice (p&lt;0.05). LPS injection significantly increased expression of activated microglia markers CD45, CD14, and Iba1. Conclusions: In a mouse model of cerebral amyloid angiopathy, acute inflammatory stimulus induced expansion of CMB without producing fresh hemorrhage. Increased size of CMB was associated with indices of cerebral edema, alteration of tight junction constituents, and microglial activation. These findings suggest that cerebral edema may mediate expansion of cerebral microbleeds.

Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice

Zingerone, one of the active components of ginger, is a phenolic alkanone with antioxidant and anti-inflammatory properties. In the present study, we analyzed the role of zingerone against RAW 264.7 cells and acute lung injury induced by lipopolysaccharide (LPS) in mice. RAW cells or BALB/c mice were pretreated with zingerone one hour before stimulated with LPS. We found that zingerone significantly inhibited the production of LPS-induced proinflammatory cytokines in vitro and in vivo. When pretreated with zingerone, pulmonary histopathologic changes, as well as alveolar hemorrhage and neutrophil infiltration were substantially suppressed in lung tissues, with evidence of reduced myeloperoxidase (MPO) activity in murine acute lung injury model. The lung wet-to-dry weight (W/D) ratios, as the index of pulmonary edema, were markedly decreased by zingerone pretreatment. Furthermore, we demonstrated that zingerone attenuates the mitogen-activated protein kinases (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways through blocking the phosphorylation of ERK, p38/MAPK and IκBα, NF-κB/P65. These results suggest that zingerone may provide protective effects against LPS-induced ALI.

Differentiation of benign angiomatous and microcystic meningiomas with extensive peritumoral edema from high grade meningiomas with aid of diffusion weighted MRI.

Objective. To determine whether angiomatous and microcystic meningiomas which mimic high grade meningiomas based on extent of peritumoral edema can be reliably differentiated as low grade tumors using normalized apparent diffusion coefficient (ADC) values. Methods. Preoperative magnetic resonance imaging (MRI) of seventy patients with meningiomas was reviewed. Morphologically, the tumors were divided into 3 groups. Group 1 contained 12 pure microcystic, 3 pure angiomatoid and 7 mixed angiomatoid and microcystic tumors. Group 2 included World Health Organization (WHO) grade II and WHO grade III tumors, of which 28 were atypical and 9 were anaplastic meningiomas. Group 3 included WHO grade I tumors of morphology different than angiomatoid and microcystic. Peritumoral edema, normalized ADC, and cerebral blood volume (CBV) were obtained for all meningiomas. Results. Edema index of tumors in group 1 and group 2 was significantly higher than in group 3. Normalized ADC value in group 1 was higher than in group 2, but not statistically significant between groups 1 and 3. CBV values showed no significant group differences. Conclusion. A combination of peritumoral edema index and normalized ADC value is a novel approach to preoperative differentiation between true aggressive meningiomas and mimickers such as angiomatous and microcystic meningiomas.

The lion's mane sign: surgical results using the bilateral fronto-orbito-nasal approach in large and giant anterior skull base meningiomas

Concerns about extreme peritumoral edema and its ensuing surgical and perioperative complications led the authors to use the bilateral fronto-orbito-nasal approach to remove midline anterior skull base meningiomas that were larger than 4 cm. The authors hypothesize that extreme vasogenic edema exemplified by finger-like hyperintensities extending into the bifrontal white matter and external capsule and/or the extreme capsule, coined the lion's mane sign (LMS), would help identify patients with a challenging postoperative course. They hypothesize that the LMS would better predict symptomatic postoperative cerebral edema than the edema index (EI). This is an observational case series of 9 patients. The authors noted the grade, pathology, tumor volume, EI, and the presence or absence of the LMS in all tumors. They used the intensive unit care (ICU) length of stay as a nonspecific measure reflecting postoperative symptomatic cerebral edema. Comparisons of edema-related postoperative complications and the EI were made between patients with and without an LMS. Bifrontal hyperintensities, extending into at least three-eighths of the length of the external capsules on T2-weighted MRI, seen in 4 of 9 patients, portended a longer postoperative ICU stay. The presence of an LMS better predicted postoperative complications related to cerebral edema than tumor grade, pathology, volume, or EI. The LMS predicts an increased duration of stay in the ICU after a bilateral fronto-orbito-nasal approach for resection of large and giant anterior skull base meningiomas. Furthermore, the LMS better predicted increased length of stay in the ICU than did the EI.

Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws.

Study on Lung Cancer Cells Expressing VEGFR2 and the Impact on the Effect of RHES Combined With Radiotherapy in the Treatment of Brain Metastases

IntroductionBrain metastases are often accompanied by edema. Endostatin therapy can prevent tumor tissue edema. Therefore, we investigated the therapeutic effects of endostatin combined with radiotherapy in the treatment of brain metastases of non–small cell lung cancer (NSCLC) and assessed the relations between the effect and vascular endothelial growth factor receptor 2 (VEGFR2) expression. Patients and MethodsEighty patients with brain metastases of NSCLC were randomly divided into a combination therapy group and a radiotherapy-alone group, each group with 40 patients. The short-term effective rate, overall survival time, cerebral edema index, and adverse reactions were observed, and the expressions of VEGFR2 protein and KDR gene in primary lesions were detected via immunohistochemical methods and fluorescence in-situ hybridization (FISH) in all patients. ResultsCompared with the radiotherapy-alone group, brain edema was significantly relieved (P = .003) and there were no marked adverse reactions in the combination therapy group. Regarding the short-term effective rate, there was no statistical significance in the total population (n = 80, 90% vs. 75%, P = .07), but there was statistical significance in cases of positive VEGFR2 (93% vs. 67.7%, P = .012) or positive KDR gene (94.4% vs. 47.3%, P = .002) in both groups. For overall survival time, there was no statistical significance in total population (n = 80, P = .35), positive VEGFR2 patients (P = .109), and positive KDR gene patients (P = .147). ConclusionCompared with radiotherapy alone, endostatin combined with radiotherapy can relieve brain edema in patients with brain metastases of NSCLC and can obtain a better short-term effective rate in patients with positive VEGFR2 or positive KDR gene, but endostatin therapy does not significantly improve overall survival time.

Bladder pain relief by HMGB1 neutralization and soluble thrombomodulin in mice with cyclophosphamide-induced cystitis

High mobility group box 1 (HMGB1), one of damage-associated molecular patterns (DAMPs), plays roles in not only inflammation but also processing of somatic pain. Given that no evidence for roles of HMGB1 in visceral pain signaling is available, we asked if HMGB1 participates in bladder pain accompanying cystitis caused by cyclophosphamide in mice, using the anti-HMGB1 neutralizing antibody and recombinant human soluble thrombomodulin (rhsTM) that sequesters HMGB1 and promotes its degradation by thrombin. Cyclophosphamide, administered i.p., caused bladder pain-like nociceptive behavior and referred hyperalgesia accompanying cystitis symptoms including increased bladder weight, an indicator of edema, in mice. The cyclophosphamide-induced bladder pain and referred hyperalgesia, but not increased bladder weight, were prevented by i.p. preadministration of the anti-HMGB1 neutralizing antibody or rhsTM. HMGB1, given i.p., facilitated the bladder pain and referred hyperalgesia caused by a subeffective dose of cyclophosphamide, an effect blocked by rhsTM. In the cyclophosphamide-treated mice, HMGB1 levels greatly decreased in the bladder tissue, particularly in the urothelial cells, but did not change in the plasma. Low molecular weight heparin, known to inhibit the receptor for advanced glycation end products (RAGE), but not lipopolysaccharide from Rhodobacter sphaeroides, an inhibitor of toll-like receptor 4 (TLR4), blocked the cyclophosphamide-induced bladder pain and referred hyperalgesia. Thus, our data indicate involvement of HMGB1 in the cyclophosphamide-induced bladder pain signaling, but not cystitis itself, and suggest that targeting HMGB1 with rhsTM or blocking RAGE might serve as a novel therapeutic strategy for the management of bladder pain.

Recombinant human endostatin combined with radiotherapy in the treatment of brain metastases of non-small cell lung cancer

Since brain metastases (BM) is often accompanied by edema, and endostatin (ES) can prevent tumor tissue edema, we investigated the therapeutic effects of ES combined with radiotherapy in the treatment of BM of NSCLC. We also determined the patients who are suitable for this therapy. Eighty patients with BM of NSCLC were randomly divided into combination group and radiotherapy alone group. The primary endpoint was overall response rate, and secondary endpoints were overall survival time, cerebral edema index and adverse reactions. These were observed and the expressions of vascular endothelial growth factor receptor 2 (VEGFR2) protein and KDR gene in primary lesions were detected with immunohistochemical method and fluorescence in situ hybridization. Compared with radiotherapy alone, brain edema was significantly reduced in the ES group (P = 0.003) without marked adverse reactions. For the overall response rate, there was no statistical significant difference between the two groups (control, 90 % vs. ES, 75 %, P = 0.07), but there was statistical significance in the patients with positive VEGFR2 (93 vs. 67.7 %, P = 0.012) or positive KDR gene (94.4 vs. 47.3 %, P = 0.002). In overall survival time, there was no statistical significance in the two groups (P = 0.35), in the tumors with positive VEGFR2 (P = 0.109) or with positive KDR gene (P = 0.147). Compared with radiotherapy alone, ES combined with radiotherapy can reduce brain edema in NSCLC patients with BM and obtain better short-term response rate in tumors with positive VEGFR2 or positive KDR gene, but does not improve the overall survival.

Biphasic inflammatory effects of Voacanga globosa ethanolic leaf extract in ICR mice

Voacanga globosa is an endemic plant traditionally used as remedy for boils in the Philippines. Four concentrations of the ethanolic leaf extracts (0.5, 5, 50 and 100 mg/kg bw) were administered intraperitoneally to 6 to 8 weeks old female imprinting control region (ICR) mice. Mice treated with 5 mg/kg bw V. globosa extract significantly potentiated the inflammatory response, exhibiting the highest edema index and enhanced leukocyte infiltration and hypertrophy. Inflammatory response was reduced at higher concentrations, suggesting that V. globosa might be immunosuppressive at high concentrations. These indicate that the ethanolic leaf extract of V. globosa exhibit biphasic inflammatory effects since it appears immunostimulatory at low concentration and immunosuppressive at high concentrations. Key words: Voacanga globosa, delayed-type hypersensitivity test, biphasic response, immunomodulation, histopathology, ICR mice.

P.17.4 Magnetic Resonance Imaging (MRI) to evaluate the effect of enzyme replacement therapy in Late Onset Pompe Disease (LOPD)

Pompe disease is a rare, progressive and often fatal neuromuscular disorder resulting from mutations in the gene for acid alpha-glucosidase (GAA), an enzyme necessary to degrade glycogen. The deficiency or dysfunction of the GAA enzyme leads to lysosomal glycogen accumulation in multiple tissues and results in cardiac and skeletal muscle dysfunction. Glycogen content may vary between muscle groups and in regions of the same muscle. Most importantly, glycogen content may change during the course of the disease. Enzyme replacement therapy (ERT) is the only FDA approved treatment for Pompe disease. However, translation from preclinical to clinical studies is challenged by the lack of reliable, noninvasive outcome measures suitable for repeated evaluations. Effect of treatment is commonly measured by muscle glycogen clearance using biochemical assays, which rely on muscle biopsy. In this study, we used Magnetic Resonance Imaging (MRI) of the thigh and lower leg muscles to evaluate the effect of 12 and 24 weeks of ERT in individuals affected by Late Onset Pompe Disease (LOPD) (n = 4; age 35–50). Maximum cross-sectional area (CSAmax) – an index of muscle mass – increased in average by 1.16- and 1.09-fold at 12 weeks, and by 1.13- and 1.09-fold at 24 weeks in the lower and upper legs respectively. In addition, we studied the MR proton traverse relaxation time (T2) – an index of muscle damage and edema – by applying a mono exponential decay equation to four echo times (TE). At 24 weeks, T2 values reduced by 1.20- and 1.10-fold in the lower and upper legs, respectively. These data demonstrate an increase in CSAmax associated accompanied by a reduction of T2 value, which may suggest a reduction of glycogen accumulation and an increase of contractile myofibers. In support of this hypothesis, biochemical assay from muscle biopsy specimens showed a reduction of glycogen concentration by 2.21-fold at week 24 compare to baseline.

Pre-Existing Hypoxia Is Associated with Greater EEG Suppression and Early Onset of Evolving Seizure Activity during Brief Repeated Asphyxia in Near-Term Fetal Sheep

Spontaneous antenatal hypoxia is associated with high risk of adverse outcomes, however, there is little information on neural adaptation to labor-like insults. Chronically instrumented near-term sheep fetuses (125 ± 3 days, mean ± SEM) with baseline PaO2 < 17 mmHg (hypoxic group: n = 8) or > 17 mmHg (normoxic group: n = 8) received 1-minute umbilical cord occlusions repeated every 5 minutes for a total of 4 hours, or until mean arterial blood pressure (MAP) fell below 20 mmHg for two successive occlusions. 5/8 fetuses with pre-existing hypoxia were unable to complete the full series of occlusions (vs. 0/8 normoxic fetuses). Pre-existing hypoxia was associated with progressive metabolic acidosis (nadir: pH 7.08 ± 0.04 vs. 7.33 ± 0.02, p<0.01), hypotension during occlusions (nadir: 24.7 ± 1.8 vs. 51.4 ± 3.2 mmHg, p<0.01), lower carotid blood flow during occlusions (23.6 ± 6.1 vs. 63.0 ± 4.8 mL/min, p<0.01), greater suppression of EEG activity during, between, and after occlusions (p<0.01) and slower resolution of cortical impedance, an index of cytotoxic edema. No normoxic fetuses, but 4/8 hypoxic fetuses developed seizures 148 ± 45 minutes after the start of occlusions, with a seizure burden of 26 ± 6 sec during the inter-occlusion period, and 15.1 ± 3.4 min/h in the first 6 hours of recovery. In conclusion, in fetuses with pre-existing hypoxia, repeated brief asphyxia at a rate consistent with early labor is associated with hypotension, cephalic hypoperfusion, greater EEG suppression, inter-occlusion seizures, and more sustained cytotoxic edema, consistent with early onset of neural injury.

Change in Body Composition in Accordance With Residual Renal Function in Patients on Peritoneal Dialysis

The aim of this study is to evaluate changes in body composition in accordance with residual renal function (RRF). Two hundred forty-four patients with more than 1 year of follow-up were enrolled. The mean value of RRF at peritoneal dialysis (PD) initiation and 1 year after PD initiation was used as an indicator of the time-averaged RRF (TA-RRF). The patients were divided into 3 groups with respect to the tertile of the TA-RRF level: low tertile (n = 81), middle tertile (n = 82), and high tertile (n=81). Body composition measurement was determined from dual-energy X-ray absorptiometry and bioimpedance analysis. This analysis was performed at PD initiation and 1 year after PD initiation. Multivariate analysis showed that the high TA-RRF tertile was associated with an increase in lean mass index. Fat mass index in all tertiles and bone mineral content index in the middle and high TA-RRF tertiles were increased, but no significant difference were observed in these changes among the 3 tertiles. The edema index decreased over the 1-year PD period. The high TA-RRF tertile was associated with a lower edema index. Although there was no statistical significance, the increase in fat mass/lean mass ratio (FM/LM) attenuated as the grade of TA-RRF tertile increased. The increase in fat mass index was similar to the trend in FM/LM. TA-RRF was associated with an increase in total lean mass and a decrease in edema index.

Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice

Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1β, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1β, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.

Incidence of irregular astigmatism eligible for contact lens fitting after Descemet membrane endothelial keratoplasty

To evaluate the incidence and causes of anterior corneal surface irregularities after successful Descemet membrane endothelial keratoplasty (DMEK) and the efficacy of contact lens fitting in these cases. Tertiary referral center. Retrospective study of prospectively collected data. Eyes with a subnormal visual outcome or monocular diplopia after successful DMEK were fitted with a contact lens. These cases were evaluated with Pentacam rotating Scheimpflug camera imaging preoperatively and 6 months postoperatively, and outcomes were compared with those in a randomly selected DMEK control group. In a series of 262 surgeries, 23 eyes (21 patients) were fitted with contact lenses; the control group comprised 23 eyes. Indications for contact lens fitting included (1) obvious corneal surface irregularities due to preexisting corneal scarring, (2) surface irregularities associated withlongstanding preoperative stromal edema, and (3) undetectable optical imperfections. The postoperative corrected distance visual acuity (CDVA) with spectacles improved after contact lens correction (P<.001). Preoperative and postoperative irregularity indices were significantly higher in the contact lens group than in the DMEK control group (P<.05). Positive correlations were found between the duration of preoperative stromal edema and postoperative Scheimpflug camera indices (P<.02). After successful DMEK, 23 of 262 eyes (9%) showed subnormal spectacle CDVAand/or monocular diplopia due to corneal scarring, surface irregularities, or undetectable optical imperfections that could be managed by contact lens fitting. Prolonged preoperative corneal edema for more than 12 months may be a risk factor for diffuse irregular astigmatism after DMEK. Dr. Melles is a consultant to DORC International BV/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned.