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PubMed2006

Liquid chromatographic tandem mass spectrometry method for the quantification of miglitol in human plasma.

A rapid, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of miglitol (CAS 72432-03-2), an alpha-glucosidase inhibitor, in human plasma using gabapentin (CAS 60142-96-3) as internal standard (IS). Following protein precipitation, the analytes were separated using an isocratic mobile phase on a reversed phase phenyl column and analyzed by MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 208/146 for miglitol and m/z 172/154 for the IS. The assay exhibited a linear dynamic range of 100-6000 ng/mL for miglitol in human plasma. The lower limit of quantification was 100 ng/mL with a relative standard deviation of less than 5 %. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The average absolute recoveries of miglitol and the IS from spiked plasma samples were 40.5 +/- 2.7 and 47.1 +/- 2.9 %, respectively. A run time of 2.5 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies. The miglitol plasma concentration profile could be obtained for pharmacokinetic study. The observed maximum plasma concentration (Cmax) of miglitol (100 mg oral dose) is 1740 ng/mL, time to observed maximum plasma concentration (tmax) is 3.5 h and elimination half-life (t(1/2)) is 2.5 h.

1-Deoxynojirimycin↗
PubMed2006

Quantification of oxcarbazeipine and its active metabolite 10-hydroxycarbazepine in human plasma by high-performance liquid chromatography.

A simple, sensitive and selective high-performance liquid chromatography (HPLC) method with ultraviolet detection (230 nm) was developed and validated for the quantification of oxcarbazepine (CAS 28721-07-5), a new antiepileptic drug, and its active metabolite 10-hydroxycarbazepine (CAS 29331-92-8) in human plasma. Following solid-phase extraction, the analytes and internal standard (zaleplon, CAS 151319-34-5) were separated using an isocratic mobile phase on a reverse phase C18 column. The lower limit of quantification was 50 ng/mL for oxcarbazepine and 100 ng/mL for 10-hydroxycarbazepine with a relative standard deviation of less than 10%. A linear dynamic range of 50 to 5000 ng/mL for oxcarbazepine and of 100 to 10000 ng/mL for 10-hydroxycarbazepine was established. This HPLC method was validated with between-batch precision of 0.8 to 8.6% and 3.2 to 7.5% for oxcarbazepine and 10-hydroxycarbazepine respectively. The between-batch accuracy was 94.0 to 102.4% and 95.4 to 105.6%, respectively. Stability of oxcarbazepine and 10-hydroxycarbazepine in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method is sensitive, simple and repeatable enough to be used in pharmacokinetic studies.

Anticonvulsants↗
PubMed2000

Biochemical activities of extracts from Hypericum perforatum L. 5th communication: dopamine-beta-hydroxylase-product quantification by HPLC and inhibition by hypericins and flavonoids.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.) exhibit beneficial effects on patients suffering from mental depressions. Lack of catecholamine neurotransmitters may be one biochemical mechanism for this problem under discussion. It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 of 0.1 mumol/l on the basis of total hypericin content and with an I50 of 21 mumol/l with pure commercial hypericin. As test system polarographic determination of oxygen uptake with tyramine as a substrate analogue was used. In the present paper the quantification of the enzymatic activity and the potential influence of inhibitors are reported using dopamine as substrate and product (noradrenaline) quantification by HPLC. With this test system it could be shown that D-beta-H is strongly inhibited by pseudohypericin (I50 = approx. 3 mumol/l) and hypericin (I50 = approx. 5 mumol/l), whereas the I50-values of various flavonoids (quercitrin, isoquercitrin, hyperoside, rutin, quercetin, amentoflavone, kaempferol) are in the range of 50 mumol/l or higher.

Anthracenes↗
PubMed2000

[Detection and quantification of coronary calcification: an update].

The demonstration of calcification of the coronary arterial wall indicates the presence of coronary heart disease (CHD). The prevalence of coronary calcifications increases with age. The extent of the calcifications correlates with the total coronary plaque burden and with the probability of a future myocardial infarction in symptomatic patients. In asymptomatic subjects with risk factors for a myocardial event demonstration of coronary calcifications is diagnostic for coronary atherosclerotic disease before clinical manifestation of the disease. Exact quantification of coronary arterial calcifications (calcium scoring) has become possible with electron beam computed tomography (EBCT) or ECG triggered subsecond CT scanners. Further improvements in the detection of coronary calcifications can be expected with the introduction of multi-slice CT. The prognostic relevance of coronary calcium scoring in asymptomatic high-risk patients is not yet clearly defined. It remains to be clarified whether newer, volume based methods of calcium quantification will be superior to the classic calcium score (Agatston-Score) for risk assessment and follow-up in this patient group.

Calcinosis↗
PubMed2002

[Comparison between biventricular cine MRI and MR flow quantification in ascending aorta and pulmonary outflow tract for the assessment of intracardial shunt volumes].

PURPOSE: Comparison between biventricular volumetric measurements and flow measurements in ascending aorta (Ao) and pulmonary outflow tract (Pu) for quantification of intracardial shunts, and evaluation of the combination of biventricular cine MRI with flow measurements for the assessment of RV and LV heart failure and valvular regurgitation (VR). MATERIAL AND METHODS: In 24 patients, right (RV) and left (LV) ventricular volumetric and flow measurements were performed in the Ao and Pu to assess the ratio of RV stroke volume (SV) or, respectively, pulmonary SV to LV SV or, respectively, systemic aortic SV (Qp/Qs). 34 patients without echocardiographically proven shunt or VR served as control group for measurement accuracy. Left-to-right shunt ratios were calculated from RV and LV SV, Pu and Ao SV, Pu and LV SV, and RV and Ao SV. Left ventricular VR was calculated by the difference of LV SV and Ao SV, and right ventricular VR by the difference of RV SV and Pu SV. Global systolic function was evaluated by biventricular cine MRI. RESULTS: Intracardial shunts with Qp/Qs > 1.16 can be quantified by flow measurements in Ao and Pu. Using biventricular volumetric measurements in cases without VR, requires a Qp/Qs > 1.21. 17 of 18 intracardiac shunts were identified on MRI, and all 8 hemodynamically significant shunts were quantitatively confirmed. The diagnosis of complete shunt closure or absent shunt was correctly made in all 6 cases. RV EF reduction was found in 6 of 24 patients. LV EF reduction was also found in 6 of 24 patients. CONCLUSION: Flow measurements in Ao and Pu are more accurate than biventricular cine MRI for the assessment of Qp/Qs ratios. Flow measurements in Ao and Pu combined with biventricular cine MRI enables the quantification of hemodynamic significant shunts, higher grade VR and biventricular global systolic function with a single examination.

Adolescent↗
PubMed2003

Quantification of the flavonoid glycosides in Passiflora incarnata by capillary electrophoresis.

Capillary electrophoresis has been applied for the separation and quantification of the flavonoids in Passiflorae herba. Separations were performed using 25 mM sodium borate with 20 % methanol (pH 9.5). For the quantification quercetin 3-O-arabinoside was used as internal standard. The method was applied to the determination of the flavonoid glycosides in 10 different commercial samples of the drug and showed similar flavonoid patterns, but differences concerning the single and total amounts of flavonoids. The total flavonoid contents determined with the new method correlated satisfactorily with those achieved by the spectrophotometric assay according to the European Pharmacopoeia.

Borates↗
PubMed2004

[Fully automatic detection and quantification of emphysema on thin section MD-CT of the chest by a new and dedicated software].

PURPOSE: Introduction of a novel software tool (YACTA -- yet another CT analyzer) for detection and quantification of pulmonary emphysema in thin-slice chest MDCT data sets. MATERIALS AND METHODS: Consisting of grey-level threshold-based algorithms (e. g., region-growing), expert rules and morphological image postprocessing YACTA segments the tracheobronchial tree prior to the detection and quantification of pulmonary emphysema. In addition to general parameters, such as the mean lung density (MLD) and the emphysema index (EI -- also described as pixel index PI), the previously described bullae index (BI) is transformed into a three-dimensional parameter for a morphological description of emphysema. A first evaluation of chest MDCT data sets of 11 patients was performed as well as a comparison of MLD, lung volume (LV), emphysema volume (EV) and PI calculated with two established commercial tools of Siemens Medical Solutions (Volume and Pulmo). Furthermore, the BI was calculated with YACTA. RESULTS: YACTA processed the image data without manual interaction and demonstrated more user-comfort than Volume and Pulmo software, which require manual correction especially for lung segmentation at the hilar regions to separate central airways from lung parenchyma. MLD, LV, and EV values calculated with YACTA were systematically higher (Pulmo: + 50 HU/+ 597 ml/+ 159 ml; Volume: + 32 HU/+ 110 ml/+ 155 ml). Different segmentation algorithms are responsible for this: YACTA includes areas not assessed by mere threshold-based techniques. Constantly lowered LV values of Pulmo are caused by a missing dilatation algorithm. The error correction as a special feature of YACTA results in increased emphysema volumes and indices. The segmentation of the tracheobronchial tree lowers the part of airways falsely classified as emphysema. CONCLUSION: The new developed software shows higher user comfort as established by semi-automated tools. RESULTS: of LV, EV, MLD and PI are comparable or moderately different. Automatic calculation of a BI is possible, providing information about bullous morphology of pulmonary emphysema. Further studies are necessary to correlate data with clinical or pathological parameters.

Adult↗
PubMed2006

[Quantification of pulmonary emphysema in multislice-CT using different software tools].

PURPOSE: The data records of thin-section MSCT of the lung with approx. 300 images are difficult to use in manual evaluation. A computer-assisted pre-diagnosis can help with reporting. Furthermore, post-processing techniques, for instance, for quantification of emphysema on the basis of three-dimensional anatomical information might be improved and the workflow might be further automated. MATERIALS AND METHODS: The results of 4 programs (Pulmo, Volume, YACTA and PulmoFUNC) for the quantitative analysis of emphysema (lung and emphysema volume, mean lung density and emphysema index) of 30 consecutive thin-section MSCT datasets with different emphysema severity levels were compared. The classification result of the YACTA program for different types of emphysema was also analyzed. RESULTS: Pulmo and Volume have a median operating time of 105 and 59 minutes respectively due to the necessity for extensive manual correction of the lung segmentation. The programs PulmoFUNC and YACTA, which are automated to a large extent, have a median runtime of 26 and 16 minutes, respectively. The evaluation with Pulmo and Volume using 2 different datasets resulted in implausible values. PulmoFUNC crashed with 2 other datasets in a reproducible manner. Only with YACTA could all graphic datasets be evaluated. The lung volume, emphysema volume, emphysema index and mean lung density determined by YACTA and PulmoFUNC are significantly larger than the corresponding values of Volume and Pulmo (differences: Volume: 119 cm(3)/65 cm(3)/1 %/17 HU, Pulmo: 60 cm(3)/96 cm(3)/1 %/37 HU). Classification of the emphysema type was in agreement with that of the radiologist in 26 panlobular cases, in 22 paraseptalen cases and in 15 centrilobular emphysema cases. CONCLUSION: The substantial expenditure of time obstructs the employment of quantitative emphysema analysis in the clinical routine. The results of YACTA and PulmoFUNC are affected by the dedicated exclusion of the tracheobronchial system. These fully automatic tools enable not only fast quantification without manual interaction, but also a reproducible measurement without user dependence.

Adolescent↗
PubMed1998

Quantification of cyclical fluctuations in cerebral blood volume in healthy infants.

Cyclical fluctuations in cerebral blood flow velocity in Doppler measurements are a well known phenomenon. In 1992 Livera et al have shown in one patient, that cyclical fluctuations of cerebral blood volume could be measured with near infrared spectroscopy (NIRS). The aim of the present study was a quantification of the amplitude of cyclical fluctuations of cerebral blood volume (represented by total haemoglobin [Hbtot]) in a large number of healthy infants. Furthermore changes of oxygenated haemoglobin (HbO2) and deoxygenated haemoglobin (Hb) were investigated. Measurements were done during two hours of undisturbed daytime sleep. Fifty-eight infants (30 male, 28 female) were included in the study. All but one infant showed cyclical fluctuations. For quantification of cyclical fluctuations only periods during quiet sleep with excellent tracing quality were used. A number of 7894 cycles was analyzed for each of the three NIRS parameters. The median amplitude of the cycling fluctuations was: delta Hbtot 1.1 mumol/l, delta HbO2 1.1 mumol/l, and delta Hb 0.2 mumol/l. The frequency was changing within a range of 3 to 6 cycles/minute. Polynominal regression analysis showed that the relationship of delta HbO2 and delta Hbtot was distinctively stronger compared to the relationship of delta Hb and delta Hbtot. In conclusion we think that these data represent "normal ranges" for parameter fluctuations in long-time NIRS tracings.

Blood Volume↗
PubMed1991

[Value of supine thoracic radiography in the diagnosis and quantification of pleural effusions: comparison with sonography].

The purpose of this prospective study was to verify the value of the supine chest radiograph with regard to the recognition and quantification of pleural effusions. The findings of supine chest radiographs were compared to those of chest sonography in a total of 320 pleural cavities. The correct identification and quantification of a pleural effusion was possible by supine chest radiograph alone in only 55% of cases (176/320). In 20% (64/320) supine chest x-ray was falsely negative and in 15% (48/320) falsely positive. In 10% an existing effusion was in fact recognised on supine chest x-ray; however the amount of effusion was wrongly estimated.

Adolescent↗
PubMed1996

[Quantification of cystoid changes in diabetic macular edema].

BACKGROUND: Cystoid changes in diabetic macular oedema can result in severe visual consequences and were previously difficult to quantify. This study was performed to introduce reliable measurements of the area covered by cysts, of their quantification and relation to visual acuity. PATIENTS AND METHODS: 58 diabetic patients suffering from cystoid macular oedema were examined by means of a scanning laser ophthalmoscope. Fluorescein angiography provides a detailed recognition of well demarcated cystoid formations in the early transit. In three different sampling areas from the center of the fovea (1.2 deg, 2.5 deg and 5 deg) and in the foveal avascular zone (FAZ) itself the area covered by cystoid changes was quantified as well as the number of cysts and their shortest distance from the center of the FAZ. RESULTS: The mean area covered by cystoid formations in the 2.5 degrees area was 0.128 +/- 0.08 micron2, the number of cysts ranged from 1 to 7. In all sampling areas there was a significant correlation between area of cysts and visual acuity. Their number and distance from the center of the FAZ did not show a significant correlation to vision. Measurements within the 2.5 degrees area seem to have the highest predictability concerning visual function. CONCLUSION: Fluorescein angiography allows the quantification of number and area covered by cystoid formations in patients with diabetic macular oedema. There is a significant correlation of visual acuity to the area covered by these cystoid changes. The distance of cysts from the center of the FAZ does not correlate significantly to visual acuity. These measurements can prove useful in following cystoid changes and in monitoring the effect of currently used therapy regimen.

Adult↗
PubMed1994

[Noninvasive quantification of aortic and mitral insufficiency. Comparison of dynamic magnetic resonance imaging and Doppler color echocardiography].

The degree of valvular regurgitation was measured by dynamic magnetic resonance imaging (MRI) and colour-Doppler echocardiography (CDE) in 23 patients (14 men, 9 women; mean age 53 [19-75] years) with aortic (n = 13) or mitral (n = 10) regurgitation. Quantification by MRI was from a section corresponding to the four-chamber view. In aortic regurgitation, maximal regurgitant jet area (JA), ratio of JA to left-ventricular area (JA/LVA) were measured, while in mitral regurgitation, the ratio of JA to left atrial area (JA/LAA) was measured, as well as jet volume (JV) and the ratio of JV to the corresponding volume of the receiving chamber (JV/LVV or JV/LVA). The results were compared with corresponding measurement obtained by CDE in the four-chamber view. The degree of regurgitation was graded as small if JA/LVA or JA/LAA, respectively, was less than 0.2, moderate if 0.2-0.4, and marked if more than 0.4. In the patients with aortic regurgitation the correlation between the two methods was r = 0.91 regarding the jet area, 0.93 regarding JA/LVA and 0.92 regarding JV/LVV and JA/LVA. For mitral regurgitation the r values were 0.93 for JA, 0.89 for JA/LAA, and 0.85 for JV/LAV to JA/LAA. The grading of aortic regurgitation by MRI and CDE agreed in 12 of 13 patients (92%), and in nine of ten (90%) with mitral regurgitation (deviation by one degree of severity in each). These data indicate that quantification of aortic and mitral regurgitation gives similar results with MRI and CDE: thus, MRI is an equal substitute to CDE in patients with inadequate conditions for sonography.

Adult↗
PubMed2002

Direct quantification of transmitral flow volume with dynamic 3-dimensional digital color Doppler: a validation study in an animal model.

Accurately quantifying transmitral flow volume is clinically important not only as a measure of cardiac output, but also as a value from which to subtract aortic flow, for determining the severity of mitral regurgitation. However, controversy exists over the accuracy of pulsed Doppler for mitral flow quantification because of the complexity of mitral flow geometry and dynamic changes in flow profile and flow area. To explore the feasibility of directly quantifying transmitral flow volume with a newly developed dynamic 3-dimensional digital color Doppler technique, this in vivo experimental study was conducted to validate the method. Eight open chest sheep were imaged with a multiplane transesophageal (TEE) probe placed on the heart for digital 3-dimensional gated acquisition of mitral inflow over a 180-degree acquisition. The digital velocity data were contour detected for flow area after computing the velocity vectors and flow profile perpendicular to a spherical 3-dimensional surface across the mitral annulus. Flow areas and actual velocities were then integrated in time and space and the resulting flow volumes were compared with those obtained by a reference electromagnetic flowmeter on the aorta for 26 steady hemodynamic states. The flow volumes correlated closely to the electromagnetic references (y = 0.87x + 2.49, r = 0.92, SEE = 1.9 Ml per beat). Our study shows that transmitral flow volume can be accurately determined in vivo by this dynamic 3-dimensional digital color Doppler flow quantification method.

Animals↗
PubMed2003

Quantification of regional myocardial perfusion using semiautomated translation-free analysis of contrast-enhanced power modulation images.

Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-frame realignment of regions of interest. We developed a technique for semiautomated identification of myocardial regions from power modulation images as a potential tool for quantification of myocardial contrast enhancement. This approach was tested in 13 anesthetized pigs during continuous intravenous infusion of contrast at baseline, left anterior descending coronary artery occlusion, and reperfusion. Regional pixel intensity was calculated for each consecutive end-systolic frame after a high-energy ultrasound impulse, and fitted with an exponential function. Perfusion defects caused by occlusion of left anterior descending coronary artery were confirmed by a significant decrease in both postimpulse steady-state intensity and the initial rate of contrast replenishment (P <.05), which were reversed with reperfusion. Automated measurements of myocardial intensity correlated highly with conventional manual tracing (r = 0.90 to 0.97), and resulted in improved signal-to-noise ratios. This technique allows translation-free quantification of regional myocardial perfusion, without the need for manual tracing.

Algorithms↗
PubMed1991

Quantification of vascular graft seeding by use of computer-assisted image analysis and genetically modified endothelial cells.

Current methods for the evaluation of retention of endothelial cells seeded on vascular grafts are limited by the inability to specifically identify and quantitate seeded cells on a long-term basis. To address this problem we developed a method of quantification of graft surface coverage using genetic labeling of endothelial cells combined with computer-assisted image analysis. Rabbit aortic endothelial cells were transduced with a marker gene (lac-Z) and seeded on polytetrafluoroethylene grafts. After histochemical staining in which the genetically labeled cells turn blue, computer-assisted image analysis was used to measure the percentage of graft surface covered by the seeded cells. The utility of the method was evaluated by using it to assess the effect on graft coverage of seeded cell density and by precoating with fibronectin. Quantification of surface area coverage was automated and reproducible both between scans and between observers. Use of this method allowed the determination of a linear correlation between cell density in the seeding suspension and graft coverage (r2 = 0.93, p less than 0.0001). The method also permitted confirmation of the positive contribution of fibronectin coating to graft coverage by seeded cells: 73% coverage coated versus 8% coverage uncoated (p less than 0.0001). The ability of this method to specifically identify genetically marked endothelial cells and their progeny makes it attractive for use in studies targeted at optimization of graft coverage in vivo.

Animals↗
PubMed2006

Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometry.

The phosphoinositide 3-kinase (PI3K)/Akt pathway controls a vast array of normal physiological processes and is frequently aberrantly activated in cancer, thus identifying PI3K/Akt-signaling components as promising drug targets in oncology. However, implementation of rational cancer therapies for this pathway needs robust and simple tools to stratify patients according to PI3K pathway activation and to validate and measure the impact of targeted inhibition on primary cancer tissues. Herein we present a technique for the quantification of the PI3K/Akt-signaling pathway based on the mass spectrometric measurement of PI3K-dependent protein kinase activity in cell lysates. The concept of this application of MS is to exploit enzymatic activity to amplify the signal of the enzyme under study analogous to the PCR used to amplify nucleic acid sequences. We show that this approach allows quantitative analysis of a cell-signaling pathway with high sensitivity, precision of quantification, and specificity. Due to its special analytical capabilities and potential for multiplexing, this approach could contribute significantly to cell-signaling studies and to the development and implementation of personalized cancer therapies.

Animals↗
PubMed2003

Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS.

A need exists for technologies that permit the direct quantification of differences in protein and posttranslationally modified protein expression levels. Here we present a strategy for the absolute quantification (termed AQUA) of proteins and their modification states. Peptides are synthesized with incorporated stable isotopes as ideal internal standards to mimic native peptides formed by proteolysis. These synthetic peptides can also be prepared with covalent modifications (e.g., phosphorylation, methylation, acetylation, etc.) that are chemically identical to naturally occurring posttranslational modifications. Such AQUA internal standard peptides are then used to precisely and quantitatively measure the absolute levels of proteins and posttranslationally modified proteins after proteolysis by using a selected reaction monitoring analysis in a tandem mass spectrometer. In the present work, the AQUA strategy was used to (i) quantify low abundance yeast proteins involved in gene silencing, (ii) quantitatively determine the cell cycle-dependent phosphorylation of Ser-1126 of human separase protein, and (iii) identify kinases capable of phosphorylating Ser-1501 of separase in an in vitro kinase assay. The methods described here represent focused, alternative approaches for studying the dynamically changing proteome.

Amino Acid Sequence↗
PubMed2002

Immunolocalization and quantification of advanced glycation end products in retinal neovascular membranes and serum: a possible role in ocular neovascularization.

PURPOSE: Earlier studies have revealed the association of advanced glycation end products (AGE) with the pathogenesis of various micro and macro vascular complications. The purpose of the present study is to localize AGEs, namely carboxy methyl lysine (CML-AGE) and methyl glyoxal-derived AGEs (MG-AGE), in retinal neovascular membranes and to quantify them in serum samples. METHODS: Surgically excised retinal neovascular membranes and serum samples obtained from patients with diabetic retinopathy, Eales' disease and nondiabetics were studied. Immunolocalization of AGEs namely CML-AGE and MG-derived AGEs was done using avidin biotin complex method and quantification was done by enzyme linked immunosorbent assay (ELISA). RESULTS: CML-AGE immunoreactivity was detected in all cases of Eales' disease and 61% cases of diabetic retinopathy and none in idiopathic epiretinal membrane (ERM). MG-AGE immunoreactivity was observed in approximately 15% of diabetic retinopathy and none in Eales' disease and and idiopathic ERM. Quantification of AGEs in serum samples revealed statistically significant increased levels of MG-AGE in diabetes, in relation to nondiabetics with idiopathic ERM and CML-AGE in Eales' disease, in relation to diabetics and nondiabetics with idiopathic ERM. CONCLUSION: Results from this study suggest that AGEs formed through glycation and glycoxidation may play an important role in the development of retinal neovascularization. The immunoreactivity of CML-AGEs in neovascular membrane and its increased levels in serum suggest that inspite of the normoglycemic status, glycoxidation and lipid peroxidation due to oxidative stress may trigger retinal neovascularization in Eales' disease, while MG-AGEs in diabetic membrane and serum suggest the role of glycation. Thus the mechanism of neovascularization in different pathological conditions could be different.

Adolescent↗