Brian J. Song

Tea Catechin Auto-oxidation Dimers are Accumulated and Retained by Caco-2 Human Intestinal Cells

Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 mumol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 mumol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% +/- 0.28% and 1.53% +/- 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% +/- 2.1% and 10.1% +/- 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% +/- 2.2% and 4.65% +/- 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% +/- 22% and 29.6% +/- 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium.

Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma.

Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue-protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials.

Mechanistic Insights into Pathological Changes in the Diabetic Retina: Implications for Targeting Diabetic Retinopathy

Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy.

Assessment of phytochemical content in human milk during different stages of lactation

OBJECTIVE The present study reports the presence of several carotenoids and flavonoids in human milk samples. METHODS Samples were collected from 17 women who delivered healthy term babies (≥ 37 wk of gestation) at 1-, 4-, and 13-wk postpartum intervals. RESULTS Epicatechin (63.7-828.5 nmol/L), epicatechin gallate (55.7-645.6 nmol/L), epigallocatechin gallate (215.1-2364.7 nmol/L), naringenin (64.1-722.0 nmol/L), kaempferol (7.8-71.4 nmol/L), hesperetin (74.8-1603.1 nmol/L), and quercetin (32.5-108.6 nmol/L) were present in human milk samples with high inter-/intraindividual variability. With the exception of kaempferol, the mean flavonoid content in human milk was not statistically different among lactation stages. In contrast, carotenoids α-carotene (59.0-23.2 nmol/L), β-carotene (164.3-88.0 nmol/L), α-cryptoxanthin (30.6-13.5 nmol/L), β-cryptoxanthin (57.4-24.8 nmol/L), zeaxanthin (46.3-21.4 nmol/L), lutein (121.2-56.4 nmol/L), and lycopene (119.9-49.5 nmol/L) significantly decreased from weeks 1 to 13 of lactation. CONCLUSION The observed differences in the relative concentrations of the two phytochemical classes in human milk may be a result of several factors, including dietary exposure, stability in the milk matrix, efficiency of absorption/metabolism, and transfer from plasma to human milk. These data support the notion that flavonoids, as with carotenoids, are dietary phytochemicals present in human milk and potentially available to breast-fed infants.

Photo- and Thermodegradation of Anthocyanins from Grape and Purple Sweet Potato in Model Beverage Systems

Recently, interest in the application of natural pigments to replace synthetic dyes in beverages has grown. The present study investigates the stability of anthocyanin-rich grape and purple sweet potato (PSP) extracts to photo- and thermostresses in ready-to-drink (RTD) beverage models including hot fill beverages with various concentrations of ascorbic acid, a preserved beverage, and a vitamin-enriched water beverage. Thermo- and photostresses were induced at 40, 60, and 80 °C and 250, 500, and 750 W/m(2), respectively. Qualitative and quantitative data on anthocyanin content were collected by pH differential assay and LC-MS. Increasing concentration of ascorbic acid caused more rapid degradation through thermostress, but had a protective effect through photostress. Additionally, PSP was significantly less stable than grape extract in the vitamin-enriched water model beverage through photostress. Furthermore, photostress caused the formation of monoacylated peonidins from diacylated peonidins.

Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model.

SCOPE Metabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome. METHODS AND RESULTS We found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity. CONCLUSION Our study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory.

New directions in the treatment of normal tension glaucoma

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.

Thermal degradation of green tea flavan-3-ols and formation of hetero- and homocatechin dimers in model dairy beverages.

Interactions between polyphenols and macromolecules may impact polyphenol stability and bioavailability from foods. The impact of milk on tea flavan-3-ol stability to thermal treatment was investigated. Single strength (36.2 protein per L), quarter strength (9.0 g protein per L) milk, and control model beverages were incubated with epigallocatechin gallate and green tea extract at 62 or 37 °C for 180 min. Intact flavan-3-ols and select auto-oxidation products [theasinesins (THSNs) and P-2 dimers] were quantified by LC-MS. Generally, greater polyphenol to protein ratios increased first order degradation rates, consequently decreasing formation of oxidation products. The presence of galloyl and hydroxy moieties was associated with higher stability of monomeric flavan-3-ols with increasing protein concentrations suggesting potential for protein affinity to stabilise flavan-3-ols to thermal treatment. Absence of these moieties led to no observable improvements in stability. These results suggest that protein interactions may be useful in stabilising flavan-3-ols through thermal processing.

Aqueous vascular endothelial growth factor and endothelin-1 levels in branch retinal vein occlusion associated with normal tension glaucoma.

Purpose:To evaluate aqueous levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in patients with branch retinal vein occlusion (BRVO) with and without normal tension glaucoma (NTG), and to assess the therapeutic efficacy of intravitreal bevacizumab (IVB) in these patients. Methods:Sixteen eyes with NTG of 48 age and sex-matched eyes without NTG that had previously received IVB for BRVO were followed for 6 months. Aqueous VEGF and ET-1 levels were measured by enzyme-linked immunosorbent assay at the time of baseline IVB. Logarithm of the minimum angle of resolution best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and then at 1, 3, and 6 months postinjection. Results:The obstruction site of BRVO was closer to the optic disk in eyes with NTG compared with controls (P=0.001). Baseline BCVA, CMT, and VEGF levels were similar between the 2 groups. Baseline ET-1 levels were significantly higher in eyes with NTG than those without NTG (P=0.009). After IVB, there was a significant improvement in both BCVA and CMT at 6 months, irrespective of the presence of NTG. However, BCVA in the presence of NTG was significantly worse at 6 months compared with eyes without NTG even though CMT was similarly reduced in both groups (P=0.04). Conclusions:Aqueous VEGF levels are similar in patients with BRVO with or without NTG, whereas aqueous ET-1 levels are elevated in the presence of NTG. Although IVB may be effective in the treatment of BRVO, the presence of NTG may limit visual recovery despite anatomic recovery of CMT.

Regional Image Features Model for Automatic Classification between Normal and Glaucoma in Fundus and Scanning Laser Ophthalmoscopy (SLO) Images

Glaucoma is one of the leading causes of blindness worldwide. There is no cure for glaucoma but detection at its earliest stage and subsequent treatment can aid patients to prevent blindness. Currently, optic disc and retinal imaging facilitates glaucoma detection but this method requires manual post-imaging modifications that are time-consuming and subjective to image assessment by human observers. Therefore, it is necessary to automate this process. In this work, we have first proposed a novel computer aided approach for automatic glaucoma detection based on Regional Image Features Model (RIFM) which can automatically perform classification between normal and glaucoma images on the basis of regional information. Different from all the existing methods, our approach can extract both geometric (e.g. morphometric properties) and non-geometric based properties (e.g. pixel appearance/intensity values, texture) from images and significantly increase the classification performance. Our proposed approach consists of three new major contributions including automatic localisation of optic disc, automatic segmentation of disc, and classification between normal and glaucoma based on geometric and non-geometric properties of different regions of an image. We have compared our method with existing approaches and tested it on both fundus and Scanning laser ophthalmoscopy (SLO) images. The experimental results show that our proposed approach outperforms the state-of-the-art approaches using either geometric or non-geometric properties. The overall glaucoma classification accuracy for fundus images is 94.4 % and accuracy of detection of suspicion of glaucoma in SLO images is 93.9 %.