Search tips
Search criteria

Results 1-12 (12)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study 
Scientific Reports  2014;4:5668.
The aim of this randomized double-blind study was to evaluate in healthy adult subjects, with functional magnetic resonance imaging (fMRI), long lasting changes in brain activation patterns following administration of a single, 250 milliseconds pulse emitted with radio-electric asymmetric conveyer (REAC) technology in the Wi-Fi bands. The REAC impulse was not administered during the scan, but after this, according to a protocol that has previously been demonstrated to be effective in improving motor control and postural balance, in healthy subjects and patients. The study was conducted on 33 healthy volunteers, performed with a 1.5 T unit while operating a motor block task involving cyclical and alternating flexion and extension of one leg. Subsequently subjects were randomly divided into a treatment and a sham treatment control group. Repeated fMRI examinations were performed following the administration of the REAC pulse or sham treatment. The Treated group showed cerebellar and ponto-mesencephalic activation components that disappeared in the second scan, while these activation components persisted in the Sham group. This study shows that a very weak signal, such as 250 milliseconds Wi-Fi pulse, administered with REAC technology, could lead to lasting effects on brain activity modification.
PMCID: PMC4092330  PMID: 25011544
2.  Metabolomic Heterogeneity of Pulmonary Arterial Hypertension 
PLoS ONE  2014;9(2):e88727.
Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.
PMCID: PMC3923046  PMID: 24533144
3.  Bone Marrow Cells Expressing Clara Cell Secretory Protein Increase Epithelial Repair After Ablation of Pulmonary Clara Cells 
Molecular Therapy  2013;21(6):1251-1258.
We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP+ cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP+ cells is beneficial after ablation of lung CCSP+ cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP+ or CCSP− BMC. Compared with mice administered CCSP− cells, mice treated with CCSP+ cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP+ cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP+ BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP+ BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised.
PMCID: PMC3677308  PMID: 23609017
4.  Vitreous TIMP-1 levels associate with neovascularization and TGF-β2 levels but not with fibrosis in the clinical course of proliferative diabetic retinopathy 
In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and CCN2 (connective tissue growth factor; CTGF) cause blindness by neovascularization and subsequent fibrosis. This angio-fibrotic switch is associated with a shift in the balance between vitreous levels of CCN2 and VEGF in the eye. Here, we investigated the possible involvement of other important mediators of fibrosis, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor (TGF)-β2, and of the matrix metalloproteinases (MMP)-2 and MMP-9, in the natural course of PDR. TIMP-1, activated TGF-β2, CCN2 and VEGF levels were measured by ELISA in 78 vitreous samples of patients with PDR (n = 28), diabetic patients without PDR (n = 24), and patients with the diabetes-unrelated retinal conditions macular hole (n = 10) or macular pucker (n = 16), and were related to MMP-2 and MMP-9 activity on zymograms and to clinical data, including degree of intra-ocular neovascularization and fibrosis. TIMP-1, CCN2 and VEGF levels, but not activated TGF-β2 levels, were significantly increased in the vitreous of diabetic patients, with the highest levels in PDR patients. CCN2 and the CCN2/VEGF ratio were the strongest predictors of degree of fibrosis. In diabetic patients with or without PDR, activated TGF-β2 levels correlated with TIMP-1 levels, whereas in PDR patients, TIMP-1 levels, MMP-2 and proMMP-9 were associated with degree of neovascularization, like VEGF levels, but not with fibrosis. We confirm here our previous findings that retinal fibrosis in PDR patients is significantly correlated with vitreous CCN2 levels and the CCN2/VEGF ratio. In contrast, TIMP-1, MMP-2 and MMP-9 appear to have a role in the angiogenic phase rather than in the fibrotic phase of PDR.
PMCID: PMC3590360  PMID: 23054594
Diabetic retinopathy; CCN2; VEGF; TGF-β; TIMP-1; MMP-2; MMP-9; Neovascularization; Fibrosis
5.  Pars plana vitrectomy for the repair of primary, inferior rhegmatogenous retinal detachment associated to inferior breaks. A comparison of a 25-gauge versus a 20-gauge system 
To compare anatomical, functional outcomes and complications of high-speed 25-gauge (G) pars plana vitrectomy (PPV) versus 20-G PPV for the management of primary inferior rhegmatogenous retinal detachment (RRD) associated to inferior breaks/holes.
Eighty-five eyes from 85 patients with a minimum follow-up of 3 months were retrospectively evaluated. Forty-one patients underwent 25-G and 44 patients underwent 20-G PPV. All patients underwent PPV with fluid-air exchange, sulfur hexafluoride (SF6) 20 % gas tamponade and laser or cryo retinopexy.
The mean follow-up interval was 6.51(±2.32) and 6.63 (±2.58) months in the 25-G and 20-G groups respectively. Single-operation success rate was 92.7 % for the 25-G group and 81.8 % for the 20-G group (P = 0.24). Post-operative hypotony was observed in no case. Redetachment occurred in 3 eyes operated on with 25-G and in 8 eyes operated on with 20-G system. All retinas were attached at final follow-up. Logarithm of the minimum angle of resolution visual acuity significantly improved from 0.69 ± 0.76 to 0.33 ± 0.37 in the 25-G and from 0.47 ± 0.59 to 0.21 ± 0.28 in the 20-G group (P = 0.0007 and P < 0.0001 respectively).
High-speed PPV and SF6 gas tamponade using either 25-G or 20-G PPV system, yields similar single operation anatomical success rates for the repair of uncomplicated, primary inferior RRDs associated to inferior breaks.
PMCID: PMC3565081  PMID: 22588289
Rhegmatogenous retinal detachment; Small-gauge vitrectomy; Inferior breaks; Sulfur hexafluoride
6.  Preliminary pilot fMRI study of neuropostural optimization with a noninvasive asymmetric radioelectric brain stimulation protocol in functional dysmetria 
This study assessed changes in functional dysmetria (FD) and in brain activation observable by functional magnetic resonance imaging (fMRI) during a leg flexion-extension motor task following brain stimulation with a single radioelectric asymmetric conveyer (REAC) pulse, according to the precisely defined neuropostural optimization (NPO) protocol.
Population and methods
Ten healthy volunteers were assessed using fMRI conducted during a simple motor task before and immediately after delivery of a single REAC-NPO pulse. The motor task consisted of a flexion-extension movement of the legs with the knees bent. FD signs and brain activation patterns were compared before and after REAC-NPO.
A single 250-millisecond REAC-NPO treatment alleviated FD, as evidenced by patellar asymmetry during a sit-up motion, and modulated activity patterns in the brain, particularly in the cerebellum, during the performance of the motor task.
Activity in brain areas involved in motor control and coordination, including the cerebellum, is altered by administration of a REAC-NPO treatment and this effect is accompanied by an alleviation of FD.
PMCID: PMC3333783  PMID: 22536071
motor behavior; motor control; cerebellum; dysmetria; functional dysmetria; fluctuating asymmetry
7.  A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy 
In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF and VEGF in the eye is associated with this angiofibrotic switch. This study investigated whether anti-VEGF agents induce accelerated fibrosis in patients with PDR, as predicted by this model.
CTGF and VEGF levels were measured by ELISA in 52 vitreous samples of PDR patients, of which 24 patients had received intravitreal bevacizumab 1 week to 3 months before vitrectomy, and were correlated with the degree of vitreoretinal fibrosis as determined clinically and intra-operatively.
CTGF correlated positively, and VEGF correlated negatively with the degree of fibrosis. The CTGF/VEGF ratio was the strongest predictor of fibrosis. Clinically, increased fibrosis was observed after intravitreal bevacizumab.
These results confirm that the CTGF/VEGF ratio is a strong predictor of vitreoretinal fibrosis in PDR, and show that intravitreal anti-VEGF treatment causes increased fibrosis in PDR patients. These findings provide strong support for the model that the balance of CTGF and VEGF determines the angiofibrotic switch, and identify CTGF as a possible therapeutic target in the clinical management of PDR.
PMCID: PMC3308470  PMID: 22289291
Angiogenesis; choroid; CTGF; diabetic retinopathy; drugs; fibrosis; imaging; macula; retina; VEGF; vitreous
8.  Heavy trypan blue staining of epiretinal membranes: an alternative to infracyanine green 
By using dyes, it is easier to identify the extent of an epiretinal membrane (ERM) or the inner limiting membrane (ILM) during surgery. Trypan blue (TB) stains ERM and ILM weakly, but with less apparent toxicity than other intraocular dyes. Its main drawback in vitreoretinal surgery is the requirement of an air–fluid exchange (AFX) before its use.
To propose a modified form of TB denser than water, thus obviating the need for an AFX.
A prospective, consecutive trial with heavy trypan blue in vitreoretinal surgery.
A consecutive group of patients with ERMs was recruited prospectively. Patients were operated on using conventional methods. Heavy TB was prepared by mixing glucose 10% with Membrane blue (Dorc, Zuidland, The Netherlands) isovolumetrically. Patients were preoperatively and postoperatively assessed at 3 and 6 months (vision and ocular coherence tomography (OCT)). Ease of surgery was also assessed.
29 eyes were included in the study. Reapplication of dye was necessary in 25% of the cases, leading to improved contrast further facilitating the peeling process. In no case was an AFX necessary to obtain sufficient staining. All patients with ERM had an improvement in vision (from median 0.30 to 0.55) and macular volume and foveal thickness (from median 450 to 238 mm) on OCT. No retinal detachment or other complications developed as a result of surgery.
Heavy TB can be delivered efficiently to the retinal surface without an AFX. Staining was sufficient to allow a safe and efficient peeling of ERM. Repeat applications were easily performed. Its use was associated with vision improvement and decreased in foveal thickness, and the absence of adverse events in this small case series.
PMCID: PMC1955665  PMID: 17576712
9.  Macular Pigment Optical Density in the Elderly: Findings in a Large Biracial Midsouth Population Sample 
To report the macular pigment optical density (MPOD) findings at 0.5° of eccentricity from the fovea in elderly subjects participating in ARMA, a study of aging and age-related maculopathy (ARM) ancillary to the Health, Aging, and Body Composition (Health ABC) Study.
MPOD was estimated with a heterochromatic flicker photometry (HFP) method in a large biracial population sample of normal 79.1 ± 3.2-year-old adults living in the Midsouth (n = 222; 52% female; 23% black, 34% users of lutein-containing supplements). Within a modified testing protocol, subjects identified the lowest and the highest target intensity at which the flicker sensation disappeared, and the exact middle of this “no-flicker zone” was interpolated by the examiner.
An MPOD estimate was obtained successfully in 82% of the participants. The mean MPOD in our sample was 0.34 ± 0.21 (SD). The interocular correlation was high (Pearson’s r = 0.82). Compared with lutein supplement users, mean MPOD was 21% lower in nonusers (P = 0.013). MPOD was also 41% lower in blacks than in whites (P = 0.0002), even after adjustment for lutein supplement use. There were no differences in MPOD by gender, iris color, or history of smoking.
Older adults in the Midsouth appear to have average MPOD and interocular correlation comparable to those in previous studies. Lutein supplement use and white race correlated with higher MPOD. No evidence of an age-related decline in MPOD was seen in the sample. The HFP method for the measurement of MPOD is feasible in epidemiologic investigations of the elderly, the group at highest risk of ARM.
PMCID: PMC2279193  PMID: 17389471
10.  Estimation of macular pigment optical density in the elderly: Test–retest variability and effect of optical blur in pseudophakic subjects 
Vision research  2007;47(9):1253-1259.
The reproducibility of macular pigment optical density (MPOD) estimates in the elderly was assessed in 40 subjects (age: 79.1 ± 3.5). Test–retest variability was good (Pearson’s r coefficient: 0.734), with an average coefficient of variation (CV) of 18.4% and an intraclass correlation coefficient (ICC) of 0.96. The effect of optical blur on MPOD estimates was investigated in 22 elderly pseudophakic subjects (age: 79.9 ± 3.6) by comparing the baseline MPOD, obtained with an optimal correction, with MPODs obtained with a ±1.00-diopter optical blur. This optical blur did not cause differences in the MPOD estimates, its accuracy, or test duration.
PMCID: PMC2271149  PMID: 17376502
Macular pigment optical density; Heterochromatic flicker photometry; Reliability; Optical blur; Aging
11.  Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice 
PLoS ONE  2008;3(1):e1527.
Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice.
Methodology/Principal Findings
Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung.
This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.
PMCID: PMC2211395  PMID: 18231608
12.  The early responses of VEGF and its receptors during acute lung injury: implication of VEGF in alveolar epithelial cell survival 
Critical Care  2006;10(5):R130.
The function of the vascular endothelial growth factor (VEGF) system in acute lung injury (ALI) is controversial. We hypothesized that the role of VEGF in ALI may depend upon the stages of pathogenesis of ALI.
To determine the responses of VEGF and its receptors during the early onset of ALI, C57BL6 mice were subjected to intestinal ischemia or sham operation for 30 minutes followed by intestinal ischemia-reperfusion (IIR) for four hours under low tidal volume ventilation with 100% oxygen. The severity of lung injury, expression of VEGF and its receptors were assessed. To further determine the role of VEGF and its type I receptor in lung epithelial cell survival, human lung epithelial A549 cells were treated with small interference RNA (siRNA) to selectively silence related genes.
IIR-induced ALI featured interstitial inflammation, enhancement of pulmonary vascular permeability, increase of total cells and neutrophils in the bronchoalveolar lavage (BAL), and alveolar epithelial cell death. In the BAL, VEGF was significantly increased in both sham and IIR groups, while the VEGF and VEGF receptor (VEGFR)-1 in the lung tissues were significantly reduced in these two groups. The increase of VEGF in the BAL was correlated with the total protein concentration and cell count. Significant negative correlations were observed between the number of VEGF or VEGFR-1 positive cells, and epithelial cells undergoing cell death. When human lung epithelial A549 cells were pre-treated with 50 nM of siRNA either against VEGF or VEGFR-1 for 24 hours, reduced VEGF and VEGFR-1 levels were associated with reduced cell viability.
These results suggest that VEGF may have dual roles in ALI: early release of VEGF may increase pulmonary vascular permeability; reduced expression of VEGF and VEGFR-1 in lung tissue may contribute to the death of alveolar epithelial cells.
PMCID: PMC1751039  PMID: 16968555

Results 1-12 (12)