*Edited by Susan L. Renes*

Traveling from Zimbabwe to New Zealand and on to Ghana and the United States, the voices of higher education are presented in a way only scholars from these regions can fully articulate and understand. The changing world of higher education challenges all of those involved in very unique ways. In Global Voices in Higher Education, scholars from 10 different countries share their work, describing not only their research but also the context in which their work exists. This book allows the reader to travel with these scholars to their colleges and universities and discover areas of concern in higher education from around the globe.

ISBN 978-953-51-3229-5

Global Voices in Higher Education

Photo by svengine / iStock


**Meet the editors**

Professor Andrew Tsin is the Chair of Biomedical Sciences Department and the Associate Dean of Research, School of Medicine, at the University of Texas Rio Grande Valley in Edinburg, Texas. His laboratory conducts research to study visual pigment regeneration and ocular diseases from diabetic complications. Professor Tsin has published more than 300 refereed research

articles and conference papers. He is a Gold Fellow of the Association for Research in Vision and Ophthalmology, a Fellow of the Royal Society of Medicine, and a Fellow of the American Association for the Advancement of Science. In 2011, Professor Tsin was presented a Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring by President Obama at the Oval Office.

Jeffery G. Grigsby is a practicing optometrist, biologist, researcher, and writer with a special interest in diabetic eye disease. In his earlier career, he provided patient care in optometric and ophthalmologic practices in West Texas. He chaired or served on 18 different Texas Optometric Association (TOA) committees and served as the president of that organization. He is a four-time re-

cipient of the TOA's Presidential Award for Service. In a mid-career shift, he currently divides his time between seeing patients, doing research, writing reviews on special interest topics in diabetic eye disease, and teaching. Currently, he serves as an adjunct faculty member at the University of Houston, College of Optometry, and a recurrent faculty member at the Texas Tech University Health Sciences Center.

Contents

**Preface VII**

Chapter 1 **Introductory Chapter: Diabetes, It is Always Something 3**

Chapter 2 **Potential Imaging Biomarkers in the Development and Progression of Diabetic Retinopathy 9**

Chapter 4 **Imaging of Hypoxia in Retinal Vascular Disease 47**

Julia Hafner, Sonja Karst and Ursula Schmidt-Erfurth

Chapter 3 **Interphotoreceptor Retinoid-Binding Protein Implications in**

Chapter 5 **Proliferative Diabetic Retinopathy: An Overview of Vitreous**

Derrick J. Feenstra, Faye M. Drawnel and Ashwath Jayagopal

Jeffery G. Grigsby and Andrew T.C. Tsin

**Section 2 Early Events in Diabetic Retinopathy 7**

**Diabetic Retinopathy 37**

**Section 3 Proliferative Diabetic Retinopathy 69**

**Immune and Biomarkers 71** Andi Arus Victor and Ratna Sitompul

Kevin Bermea

**Section 1 Introduction 1**


**Abstract**

This chapter describes a theory and application of satellite gravity and altimetry data for determining Moho constituents (i.e. Moho depth and density contrast) with support from a seismic Moho model in a least-squares adjustment. It presents and applies the Vening Meinesz-Moritz gravimetric-isostatic model in recovering the global Moho features. Internal and external uncertainty estimates are also determined. Special emphasis is devoted to presenting methods for eliminating the so-called non-isostatic effects, i.e. the gravimetric signals from the Earth both below the crust and from partly unknown density variations in the crust and effects due to delayed Glacial Isostatic Adjustment as well as for capturing Moho features not related with isostatic balance. The global means of the computed Moho depths and density contrasts are 23.80.05 km and 340.5 0.37 kg/m3 , respectively. The two Moho features vary between 7.6 and 70.3 km as well as between 21.0 and 650.0 kg/m3 . Validation checks were performed for our modeled crustal depths using a recently published seismic model, yielding an RMS difference of 4 km.

**Keywords:** crustal depth, Moho density contrast, Moho depth, Vening Meinesz-Moritz method


**2. What are anthocyanins?**

Anthocyanins belong to a class of substances known as flavonoids, one of the largest categories of phenolic compounds. The basic structure of anthocyanins is made up of a flavylium cation (C6-C3-C6), which may be attached to different sugars, as well as to hydroxyl and methoxy groups, resulting in over 635 different anthocyanins identified to date. The most common sugar associated to anthocyanins is glucose, although rhamnose, xylose, galactose, arabinose, and rutinose have also been found as part of these molecules [1]. Anthocyanins may be mono-, di-, or tri-glycosides, depending on the number of sugar molecules they contain. Durst and Wrolstad [2] reported that anthocyanins are glycoside groups that belong to the family of flavonoids; their structure contains two aromatic rings A and B, joined by a three-carbon link (**Figure 1**). The structural variations that occur in ring B result in six different anthocyanins as shown in **Table 1**.

Anthocyanins are the most important natural pigments, soluble in water, that give colors red, purple, and blue to flowers, fruits, and other parts of the plant. Besides coloring, these pigments play other roles in plants, such as attracting pollinizers in order to disperse pollen and seeds, as well as protecting the tissue against UV radiation and harmful virus and bacteria. Given the above, the scientific interest on anthocyanin pigments has increased in the past few years, particularly on their role in the reduction of heart disease, cancer, diabetes, anti-inflammatory effects, and improvement of visual acuity [3]. For centuries, these compounds have been a part of the human diet due to their attractive bright colors, anti-inflammatory, and antioxidant properties, without any evident harmful side effects. Anthocyanins are regarded as a potential alternative in the replacement of artificial food colorings, some of which have been associated to certain diseases. Several sources of anthocyanins have been studied in order to find acidified anthocyanins with greater stability at different pH conditions, at an affordable cost. Stability is a relevant factor since the color of these compounds is easily affected by several conditions, mainly pH [4]. Predominant structures of anthocyanins at different pH values are shown in **Figure 2**.

The color of anthocyanins depends on the number and orientation of hydroxyl and methoxy groups. Increases in hydroxylation produce color changes toward the blue side of the color spectrum, while increases in methoxylation produce red colorations [3].

The color changes in anthocyanins given by variations of pH are due to the glycoside substitutions (mono-, di-, or tri-saccharides) in positions 3 and/or 5 of the B ring (**Figure 1**), and this also helps to increase solubility. Some examples of glycosylated saccharides are glucose, galactose, xylose, arabinose, rutinose, sambubiose, and

**Figure 1.** *Structure of anthocyanins [2].*

#### **Table 1.**

*Substituents of the six types of anthocyanins.*

**Figure 2.** *Anthocyanins biosynthesis pathway [5].*

gentiobiose. Another cause of the color displacement toward purple in the molecule is the aromatic acylations in the position 5 of carbon B in the structure [6].

**Figure 2** shows the biosynthesis of anthocyanins as established experimentally, where ring A is synthesized via the malonic acid pathway, by condensing three molecules of the malonyl-CoA. On the other hand, ring B is synthesized via the shikimic acid pathway. The enzyme phenylalanine ammonia lyase (PAL) reacts with phenylalanine, which converts into *p*-coumaric acid by the loss of NH3. Afterward, a condensation reaction of three molecules of malonyl-CoA results in an intermediate 15-carbon compound, which is transformed into a flavanone. Then, the flavanone is converted into an anthocyanin by the hydroxylation of carbon 3 and the subsequent dehydration. Finally, the molecule is stabilized by glycosylations of the heterocycle, and the reaction is catalyzed by the glycosyl transferase enzyme and then by methylation reactions followed by acylations [7].

The use of natural anthocyanin pigments as food colorings in processed products is getting increasing attention, since they are very attractive to consumers, while having beneficial health effects. Anthocyanin pigments are permitted as natural food colors in the United States under the fruit (21 CFR 73.250) and vegetable categories (21 CFR 73.260) [8].

## **3. Anthocyanin sources**

*Hibiscus* flower (*Hibiscus sabdariffa* L.) is a source of vitamins C and E, polyphenolic acids, anthocyanins, and flavonoids, all of which are known to have antioxidant activity, as they are capable of reducing free radicals [9].

Different varieties of *Hibiscus sabdariffa* L. are available in Mexico, and each one is characterized by its anatomy, color, and physicochemical properties. The content of active compounds varies according to the chalice, as well as to the extraction method. These pigments may be an alternative to the industry of colorings, cosmetology, and processed food, while providing extra health benefits [10].

Nowadays, the food and cosmetic industries demand an ample variety of additives and colorings, in order to improve the appearance of a product and make it attractive to consumers. Industrial food colorings are found in many products that we use or buy on a daily basis, such as juice, jellies, pastries, soft drinks, paints, cosmetics, and more. Most of these additives are synthetically produced and may cause adverse health consequences: allergic reactions, digestive problems, cancer, and asthma, among others [11].

Natural food colors are found in fruits such as acai, cherries, cranberries, elderberries, raspberries, blueberries, black and blue grapes, plums, strawberries, figs, pomegranate, and red apple [12]. Other important sources are found in vegetables: beets, purple lettuce, green onion, radish, purple cabbage, red bell peppers, eggplant, as well as cereals such as blue corn (*Zea mays* L.) [13], blue wheat [14], and rice [15]. Recently, other plants and flowers have been studied as potential sources of antioxidants [16, 17], such as elder (*Sambucus nigra*) [18], perilla fruit from Japan (*Perilla frutescens*) [19], and flower petals: iris (*Iris dichotoma*, *Iris domestica*) from China [20], Damascus rose (*Rosa damascena*) [21], cyani flower (*Centaurea cyanus*) [22], dahlia (*Dahlia mignon*) [23], and viola (*Viola tricolor*) [16].

## **4. Anthocyanins as natural colorings**

The growing concern about the use of synthetic colorings in processed foods, cosmetics, and pharmaceuticals is caused by their potential harmful effects. Countries like Australia, Japan, Norway, and Switzerland have banned the use of

### *Natural vs Synthetic Colors DOI: http://dx.doi.org/10.5772/intechopen.86887*

some synthetic colorings, such as Red No. 20 and 40, since they have been related to hyperactivity in children of school age. This effect may be considered as an acute neuronal illness; however, these food additives are still being used in the United States [24].

Regulatory policies dealing with the use of colorings derived from anthocyanins vary from country to country. The United States is the most restrictive country on the use of anthocyanins as natural colorings, where four out of the 26 colorings that are approved for their use in foods are derived from grape peel, vegetable, and fruit juice [25]. In Mexico, there is no regulator policy for natural colorings at this point.

In the European Union, Chile, Colombia, Iran, Israel, South Korea, Malta, Peru, Saudi Arabia, and the Emirates, all colorings derived from anthocyanins are regarded as natural [26].