*2.2.1. Hemolysis and vasculopathy*

Hemolysis in SCD leads to release of arginase 1, asymmetric dimethylarginine and adenine nucleotides, these promote vasomotor dysfunction and proliferative vasculopathy. Circulating hemoglobin and heme both referred to as erythrocytic danger-associated molecular pattern (eDAMP) molecules activate endothelial inflammatory and angiogenesis. Hemolysis in SCD therefore leads to anemia, increased superoxide anion and reactive oxygen species (ROS) production and low ROS scavenging enzymes activity promote oxidative stress-induced vascular complications. Itokua et al. reported in their study [20] that albuminuria was associated with increased white blood cell (WBC) count and LDH enzyme levels. Oxidative damage may alter both the structure and the function of the glomerulus due to its effects on mesangial and endothelial cells. Activated circulating white blood cells and platelets express adhesion glycoproteins leading to endothelial cell adhesion molecules and endothelial dysfunction.


2.2.6. Peroxiredoxin Expression in Neuro-2a Cells by Immunoblotting

In order to evaluate the effect of urolithin A on the expression of Prx1 and Prx3, Neuro-2a were grown in 6-well culture plates and treated with 0.5–4 μM urolithin A for 24h. Twenty-four hours later, cells were washed with PBS and scraped in lysis buffer (EDTA 1 mM, Tris 25 mM, NaCl 150 mM, 0.1% Triton; PMSF, leupeptin, and pepstatin; pH = 7.4) for 20 min. Supernatants were collected for protein determination with the bicinconinc acid method and dilutions were prepared to obtain the concentrations of proteins. Then, 10 μg of protein extract per sample was mixed with Laemmli buffer with β-mercaptoethanol, loaded onto 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and subsequently transferred to nitrocellulose membranes. Immediately after this, protein transfer and loading were controlled by Ponceau red staining, followed by membrane blocking with bovine serum albumin (BSA). The following antibodies were used: anti-Peroxiredoxin 1 (ab41906; Abcam, Cambridge, UK) and anti-Peroxiredoxin 3 (AV52341; Sigma-Aldrich, St. Louis, MO, USA). Antibody binding was detected by chemiluminescence with species-specific secondary antibodies labeled with horseradish peroxidase (HRP) and visualized on a digital luminescent imager analyzer

(Fujifilm LAS-4000, Cambridge, MA, USA). Images were quantified using ImageQuant TL software (Global Life Sciences Solutions, Pittsburgh, PA, USA).


**1. Introduction**

It is well known that the classical Fourier transform refers to the decomposition of a function belonging to an appropriate space into exponentials, which can be viewed as the irreducible unitary representations of the additive group of the real numbers. However, in the current most popular interpretation, particularly in connection with non-commutative groups, the phrase *harmonic analysis* has lost its original function-theoretic meaning and now it generally refers not to functions but to representations. It thus becomes natural to regard irreducible representations as the basic building blocks of the theory in place of exponential functions [1]. There are however examples in the theory of the semi-simple non-compact Lie groups where the classical setup prevails, in the sense that one can find a class of functions which play a role similar to that played by the exponentials on the real line. A typical example thereof is the group SU(1, 1): hereafter, we shall work at the level of homogeneous spaces associated with this group and, accordingly, we shall study the spherical functions that can be constructed in these spaces.

Within this framework, a fundamental role is played by the Helgason construction of the so-called *non-Euclidean Fourier analysis* [2]. The working ambient is the symmetric space SU(1, 1)/ SO(2), i.e., the non-Euclidean disk. By the use of the Poisson kernel, the analog of the plane waves are constructed in the case of the hyperbolic disk and, successively, an integral representation of the conical functions *P*− 1 2 +i*μ*(cosh *r*) (i.e., the Legendre functions of the first kind with index (−1 2 + i*μ*), *μ* ∈ R) is derived in terms of these *hyperbolic waves*. It can thus be proved for these functions a product formula, which corresponds to the classical product formula of the exponentials. Finally, a Fourier transform on the non-Euclidean disk can be set up, which is exactly the tool analogous to the classical Fourier transform. In this connection, it is worth recalling that the conical functions can be associated with the

principal series of the irreducible unitary representation of the group SU(1, 1), which acts transitively on the hyperbolic disk.

Consider now an isotropic cone in R3. We focus on the two-sheeted hyperboloid interior to the cone. By stereographic projection, the upper sheet of the two-sheeted hyperboloid can be mapped into the interior of the unit disk. Since the connected component of the two-sheeted hyperboloid is the homogeneous space SO0(1, 2)/ SO(2), the non-Euclidean Fourier analysis coincides with the harmonic analysis on SO0(1, 2)/ SO(2). We can thus define and study the Fourier transform on the two-sheeted hyperboloid.

Harmonic analysis can be studied also on the one-sheeted hyperboloid, which is a pseudo-Riemannian symmetric space SO0(1, 2)/ SO0(1, 1). It is then possible to construct on this symmetric space spherical functions, which turn out to be the Legendre functions of the second kind. A peculiar feature of this space is that it can be equipped with the partial ordering associated with the light cone in R3: namely, *x y* ⇔ (*x* − *y*) belongs to the closed future cone of R3. The one-sheeted hyperboloid equipped with this ordering relation is a *causal symmetric space* [3]. Accordingly, we can introduce a *Volterra algebra* of kernels, i.e., kernels *K*(*x*, *y*) whose support is contained in the set Γ . = {(*x*, *y*) ∈ *X*2 × *X*2 : *x y*}, where *X*2 is the one-sheteed hyperboloid. A kernel *K* is said to be invariant under *G* ≡ SO0(1, 2) if for any *g* ∈ *G*: *K*(*gx*, *gy*) = *K*(*x*, *y*), (*x*, *y*) ∈ Γ. An invariant Volterra kernel *K* can be identified with a function *f* on *G* through the equality: *K*(*ge*2,*e*2) = *f*(*g*), where *g* ∈ *G* and *e*2 = (0, 0, 1) (see next Figure 1) is the point which features *he*2 = *e*2, with *h* ∈ SO0(1, 1) [4–7]. Successively, the *spherical Laplace transform* for this class of functions can be defined. This transform, as the ordinary Laplace transform, is holomorphic in a half-plane and, in the specific case of the spherical Laplace transform, this analyticity property follows from the analyticity property of the Legendre functions of the second kind *Qλ*(·), which are holomorphic in the half-plane C(+) (−1) . = {*λ* ∈ C : Re *λ* > −1}. These latter functions are indeed the spherical functions on ordered symmetric spaces in the sense of Faraut et al. [7].

**Figure 1.** Horocyclic fibration of the one-sheteed hyperboloid *X*+ 2 .

Another question closely related to this type of problems is the holomorphic extension associated with Fourier–Legendre expansions of the type: 14*π* ∑∞*n*=0(2*n* + 1)*anPn*(cos *θ*), where *Pn*(·) denotes the Legendre polynomials. In this paper, we prove that, if the sequence {(*n* + 1)2*an*}∞*n*=0 satisfies a suitable Hausdorff-type condition [8], then the function *f*(cos *θ*), to which the Fourier–Legendre series converges in the interval (−1, 1), admits a holomorphic extension to the complex cos *θ*-plane cut along the semi-axis [1, +∞). The first result we prove is a basic feature of the holomorphic extension associated with Fourier–Legendre series: the *dual analyticity property*. To classes of functions which are holomorphic in the cos *θ*-plane cut along [1, +∞), there correspond classes of functions, denoted *a*˜(*λ*) (*λ* ∈ C), which are expressed as a spherical Laplace transform, holomorphic in the half-plane Re *λ* > −12 , of Carlsonian-type (i.e., of suitable exponential growth; see next Theorem 1) and, therefore, unique interpolants of the coefficients *an* of the Fourier-Legendre series, i.e., *a*˜(*λ*)|*λ*=*n* = *an* (*n* = 0, 1, 2, . . .).

At this point, two strictly related problems emerge. On the one hand, the possibility of connecting, via analytic continuation, the completeness of the spherical functions for SO(3) to the completeness of the corresponding expansion of SL(2, R), which is the group acting transitively on the upper half-plane, where the model of the non-Euclidean geometry can be realized, while, on the other hand, continuing the unitary representations of SO(3) to give the unitary representations of SL(2, R). The first problem has been initially tackled by Stein and Wainger [9], while, for what concerns the second one, the reader is referred to the work of R. Hermann [10]. However, both of these problems require linking the spherical Laplace transform to the non-Euclidean Fourier analysis. When we consider the ordinary Laplace transform of a function *f* ∈ *L*1(0, +∞) ∩ *L*2(0, +∞),

$$\widetilde{f}(\lambda) = \int\_0^{+\infty} e^{-\lambda v} f(v) \, \mathrm{d}v \qquad (\lambda \in \mathbb{C}, \mathrm{Re}\,\lambda > 0),$$

we obtain for *λ* = i*μ* (*μ* ∈ R):

$$\widetilde{f}(\mathbf{i}\mu) = \int\_{-\infty}^{+\infty} e^{-i\mu v} f(v) \,\mathrm{d}v \qquad (\mu \in \mathbb{R})\_{\prime}$$

which is precisely the Fourier transform of *f*(*v*), it being well-defined in view of the assumption *f* ∈ *L*1(0, +∞). Since *f* ∈ *L*1(0, +∞) ∩ *L*2(0, +∞), the Fourier transform can be inverted to recover *f*(*v*) in terms of *f* , (i*μ*) through the *inverse Fourier transform*, which converges to *f*(*v*) as a limit in the mean order two. Correspondingly, we pass from the non-unitary representation *e*−*λv* (*λ* ∈ C, Re *λ* > 0, *μ* ≡ Im *λ* ∈ R) to the unitary irreducible representation *e*−i*μv* (*μ*, *v* ∈ R) that we mentioned at the beginning of the Introduction. This connection can be extended. One of our results consists indeed of proving that the spherical Laplace transform reduces to the non-Euclidean Fourier transform at Re *λ* = −12 , which is precisely the value corresponding to the principal series of the unitary representations of the group SU(1, 1), which acts transitively on the hyperbolic disk. This result has been obtained by establishing a bridge between the harmonic analysis on the one-sheeted hyperboloid and the harmonic analysis on the two-sheeted hyperboloid.

The harmonic analysis in causal symmetric spaces has been a subject of growing interest in the last three decades, and the research on these topics has flowed in various directions. Some papers have been devoted to the proof of the Paley–Wiener theorem for spherical Laplace transform [11,12] and others have treated the inversion problem extended up to the so-called Θ-transform [13]. In [14], Bertram has studied the compact symmetric space and its non-compact dual, both realized as real forms of their common complexification; this analysis has been performed by exploring the Ramanujan garden and by the use of the so-called *Master Theorem*. Working in a different direction, Gindinkin and Krötz [15] have studied the complex crown of Riemannian symmetric spaces and non-compactly causal symmetric spaces.

This allowed them to prove the conjecture that every non-compactly causal symmetric space occurs as a component of a distinguished boundary of some complex crown [15]. Finally, it is worth recalling that the question of relating the harmonic analysis of different real forms of a complex symmetric space has been studied also in the context of scattering theory and resonances [16–20].

The paper is organized as follows. In Section 2, we study the holomorphic extension associated with the Fourier–Legendre expansion by means of the spherical Laplace transform. We are thus led to develop the harmonic analysis on the complex one-sheeted hyperboloid *X*(*c*) 2 , which contains as submanifolds either the Euclidean sphere (iR × R2) ∩ *X*(*c*) 2 on which the Fourier–Legendre expansion can be developed, and the real one-sheeted hyperboloid, which contains the support of the cut. In Section 3, we analyze the relationship between the spherical Laplace transform and the *non-Euclidean Fourier transform*. For this purpose, we consider a real two-sheeted hyperboloid, and, in this geometrical setting, we can recover the non-Euclidean Fourier transform in the sense of Helgason. Finally, in Section 4, some conclusions will be drawn.

### **2. Holomorphic Extension Associated with the Fourier–Legendre Expansion and the Spherical Laplace Transform**

### *2.1. The Complex One-Sheeted Hyperboloid*

In the space C3 of the variable *z* = (*z*0, *z*1, *z*2), we consider the complex quadric *X*(*c*) 2with equation

$$-z\_0^2 + z\_1^2 + z\_2^2 = 1\_\prime$$

which is a one-sheeted complex hyperboloid. Next, we introduce two systems of coordinates: polar and horocyclic coordinates.


**1. Introduction**

Green energy and renewable energy are one of the most essential fundamentals for future developments of countries all over the world. Running out of fossil fuels in near future, makes the use of renewable energies almost inevitable. Evaluation of the capability of using these types of energies is an essential issue at present. Extreme dependency of mankind to the limited energy resources is both dangers and unsustainable and finding a way out is one of the most important challenges that we face. Achieving some unlimited energy sources has been human's dream. Daily increase of energy demands and limitation of fossil energy resources from one side, and increase of environmental pollutants caused by using these resources in the other side, has made application of renewable energies more essential and widespread. The wind, as one of the climatological factors has a wide effects on agriculture, transport, pollution, energy, manufacturing and industrial plans. Wind power is one of the first energy sources discovered by humans. It is applied for different purposes such as power source for ship movement, irrigation and milling in some countries such as Iran and China. However, construction of wind power plants would make this type of energy more applicable. Nowa‐ days, coal, oil and gas are the main resources to provide energy. In recent years, an increasing trend in price of the mentioned materials has become vivid due to the globalization and political events and mostly because of water crises. These increasing prices make us to find an appropriate solution to decrease the expenses and increasing the stability. Furthermore, renewable energies are considered as available, exchangeable and inexhaustible resources. New energies are available until these resources exist. Wind energy is used in two ways, first in direct way in which the wind is applied for drying and ventilation, and secondly, the wind is utilized indirectly for milling the grains, to pump water to the fields and to generate

© 2013 Fakhry et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Fakhry et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

electricity. The evidence shows that in some countries such as Iran, Iraq, Egypt, China, Italy, Spain, the wind energy has been used for milling and irrigation. According to IPCC special report on renewable energy sources and decreasing the climate change damages, there is an increasing trend in the magnitude of the wind power plants from 17 meters high and 75 kilowatts in 1980 decade to 80 meters high and 1800 kilowatts in 2005-2010. It is predicted that the size of these generators should be 250 meters high and 20000 kilowatts in future years which is clarifying the increasing trend of application of this green energy. An important challenge in front of this kind of power plants is the uncertainty in accessible capacity of electrical power. This problem has been caused by random nature of effective factors such as random variation in mechanical forces generating wind power. In other words, due to the continuous variations in meteorological and climatological conditions, the wind speed, duration, density and power are randomly changing. Thus, for using its power, it is necessary to study the windy conditions in the area and statistical data reported by meteorology centers. However, the analysis of such large amount of data recorded in meteorology centers to estimate the mechanical power input of wind power plants is not possible except using some applied methods. Obviously, the study of the behavior and speed of winds will lead to more accurate estimation of accessible capacity in wind power plants. Moreover, spatial analysis of this climatological phenomenon will provide some essential knowledge about the areas with potential capacity of constructing wind power plants. The frequency analysis is an operative tool in assessing this aim. This study is going to describe these materials and their effects on regionalization of wind speed under effect of climate change.

**Results Paper Type Location Scenarios Model References**

Case study USA A1b, A2 4 GCM

2 scenarios CCM

HWIND and SIMA

Wind Speed Regionalization Under Climate Change Conditions

Case study Indian A2 CGCM3 Deepthi and Deo (2010)

Texas and California

Sailor et al. (2008) In order to create the scenarios of changes in power density under climate change, a method is

Case study Finland A2

15 – 30 % wind speed growth Case study Brazil A1B HADCM3 Pereira et al. (2012)

Case study

developed for mapping the daily-resolution downscaled GCM output to the hourly level. The model results for either of the SRES scenarios were similar. In most cases, the impacts of the A2 scenario were slightly larger than those for the A1B scenario, but these inter-scenario differences were smaller than the inter-model differences, even after downscaling.

> Review Paper

Sailor et al. (2000)

http://dx.doi.org/10.5772/55985

217

Peltola et al. (2010)

Pryor and Barthelmie (2010)

include improved estimates of vulnerabilities in the wind power site

**Table 1.** Wind speed investigations in future period

there is an evidence for small magnitude changes in the wind resource and increases in extreme wind speeds, and the declines in sea

ice and icing frequencies.

climate impacts.

downscaling.

selection decision process. -ANN and statistical downscaling -A2 is preferred to A1b changes in daily mean wind speeds at each location and they are presented and discussed with respect to potential implications for wind power

generation.


Preface

Demyelination disorders are among the most frequent neurological conditions that affect either the central or the peripheral structures of the nervous system or non-rarely both of them. These disorders have a multifactorial causative background and result in serious physical incapacity. They induce suffering, physical inability, and psychological and mental distress in millions of patients worldwide, increasing socioeconomic burden and negatively affecting patient quality of life. The most common type of central demyelination disease is multiple sclerosis (MS), which remains an unsolved problem in the field of neurosciences with a mosaic of clinical manifestations and a long labyrinth of therapeutic approach.

Many factors cause the complicated etiological pattern of demyelinating diseases, some of which are innate and some of which are exogenous. Among the innate causes, genetic factors play a dominant role in the majority of cases of central demyelination [1] as well as in a considerable number of peripheral ones. Among a large number of exogenous agents are viral infections, dietary habits, smoking, obesity, physical or psychological trauma, latitudinal gradient and climate of a country, and ultraviolet light exposure. Genetic predispositions affecting autoimmune reactions, which are mostly mediated by T and B cells, play the most substantial role in the dramatic course and conclusion of the disease. Current therapeutic protocols are scheduled based on the autoimmune character of MS, attempting to control the activation of lymphocytes and the many cellular interactions characteristic of the disease [2].

In this volume, the authors analyze many aspects of demyelination from clinical, diagnostic, and therapeutic points of view. They describe the role of Schwann cells in the periphery and that of pericytes in the brain using experimental models, which offer the possibility of close observation and detailed study of the morphological alterations and pathogenetic mechanisms of demyelination and remyelination.

The multiform clinical manifestations of MS have a global character involving the physical, psychological, and mental aspects of the patients' life. The first chapter [3], discusses depression in patients with demyelination disease [4]. Rarely in serious cases, depression may be associated with suicidal ideation [5], whereas in the majority of cases it is related to anxiety, phobic phenomena, or even panic disorders that are proportional to the physical inability of the patients. On the contrary, some patients show emotional inertia, apathy, or absence of interest for the course of the disease. Many patients neglect environmental conditions and show behavioral changes, including euphoria [6], which might be attributed to the gradual degeneration of the frontal or prefrontal areas of the brain.

In Chapter 2, the authors discuss the non-pharmacological treatment of MS. The authors suggest that physiotherapy is a crucial and effective measure for increasing neuroplasticity and thus enabling the patient to retain functional independence. Physical education and exercises [7] may generally increase the concentration

of neurotrophic factors in the brain, enhancing synaptogenesis and improving the physical condition of patients. Among the various types of physical therapy, Judo seems to have beneficial effects in cases of relapsing-remitting (RR) MS [8], especially when incorporated at the initial stages of the disease, given that it may improve the development of proprioception, motor coordination, endurance, and muscle strength.

Chapter 3, [9], analyzes the activity of the Schwann cell, concluding that it plays a preponderant role in recovering nerve fibers after Wallerian degeneration, forming bands of Büngner, which guide the centrifugal propagation of axonal sprouts, reforming the myelin sheath and providing support for axonal outgrowth by the initiation of a reciprocal dialogue between axon and Schwan cell basal lamina by the plastic potentiality of Schwann cell [10]. Unfortunately, human Schwan cells have a limited in-time regenerative capacity and their contribution in axonal regeneration and remyelination gradually declines [11]. The authors underline that the understanding of the "extraordinary plasticity" of Schwann cells may inspire the introduction of novel therapeutic methods for the healing of peripheral neuropathies and traumatic nerve injuries.

However, all Schwan cells do not participate in the formation of the myelin sheath and the remyelination of damaged nerve fibers. Some of them, the so-called Remak fibers, are non-myelinated Schwann cells (NMSCs). Nevertheless, they have an important contribution in axonal maintenance and neuronal survival and are essential for the normal development and function of the peripheral nerves [12]. Remak fibers also play an important role in the modulation of pain sensitivity in peripheral sensory neuropathies. Chapter 4 describes in detail the different functions of Remak fibers according to their distribution in the nervous system [13]. Thus, the chapter describes their role as immune-competent cells [14] in the modulation of pain sensitivity in peripheral sensory neuropathies as well as in the formation and function of the neuromuscular junction. The authors' of this chapter conclude that a better understanding of the function of Remak fibers could lead to potential new treatment approaches to sensory neuropathies and even spinal muscular atrophy.

It is unanimously accepted that acute demyelinating polyradiculoneuropathy or Guillain Barré syndrome (GBS) is among the most serious conditions of peripheral demyelination. It is one of the main causes of flaccid paralysis in previously healthy individuals, particularly children [15]. In a considerable number of cases, respiratory infection is noticed to occur before the initiation of clinical phenomena of the disease. Chapter 5, describes an unusual case of recurrent GBS in a child who suffered from the disease in two successive episodes: from the acute inflammatory demyelinating variant in the first episode and from the acute axonal motor variant in the second one [16]. Both appeared following an episode of respiratory infection. The authors underline the value of early diagnosis based on the clinical estimation of the patient, in correlation with neurophysiological data, which should be important for the prompt therapeutic intervention of intravenous immunoglobulins (IVIGs) [17, 18].

Peripheral neuropathies are substantial causes of motor, sensory, and even autonomic disabilities with an unfavorable impact on quality of life. Among the broad etiopathological spectrum of these neuropathies, diabetic peripheral neuropathy

**V**

affects between 23% and 76% of the general population [19, 20]. Chapter 6 describes the various clinical and neuropathological types of diabetic neuropathies [21]. The authors emphasize the importance of the early clinical assessment of patients for

The vascular factor is an additional component in the broad pathogenetic background of central and peripheral demyelination. Anti-neutrophil cytoplasmic antibodies (ANCAs) may induce necrotizing vasculitis, which has polymorphic symptomatology including peripheral neuropathy in 50% of cases [23, 24]. In Chapter 7 [25] discusses the prevalence, clinical manifestations, prognosis, and treatment of peripheral neuropathies due to ANCAs, underlining that mononeuritis multiplex is the most common clinical form of peripheral neuropathy in antibodies-associated vasculitides (AAV), necessitating prompt treatment with

The mechanical lesions of the peripheral nerves are not a rare phenomenon. Compression on peripheral nerves may provoke serious functional deficits, particularly whenever it occurs for a long time at certain points along the nerves' anatomical pathways [27]. In Chapter 8, [28] the authors discuss the many types of entrapment neuropathies concerning the upper extremities. The authors present a detailed schematic topographic analysis of the vulnerable points of the nerves along their course. In addition, they offer a precise description of the clinical signs of diagnostic significance in each one of the syndromes of entrapment neuropathies, highlighting the substantial role that anatomical variations, trauma, metabolic diseases, tumors, synovitis, and vitamin B6 deficiency play, among others, in their

The main doctrine in medicine based on the Hippocratic aphorism οφελέειν ή μη βλάπτειν is the alleviation of human suffering and the improvement of the quality of life of patients. For the realization of this doctrine, according to Galen, experimental research is essential for further understanding of the pathogenetic mechanisms of diseases and subsequent tracing of new proper and efficient therapeutic approaches. In the field of demyelinating diseases, the development of experimental models of demyelination and remyelination in vitro and in vivo is a necessity [30]. Given that MS has a dominant place in the spectrum of demyelinating disorders, several models of experimental encephalomyelitis have been introduced, approximating the clinical and neuropathological phenomena of the disease [31]. Many of those models, such as experimental autoimmune encephalomyelitis (EAE), toxic, viral, and transgenic models, are described in Chapter 9 [32], which emphasize the value of understanding MS via patient data.

Finally, Chapter 10 discusses the role of pericytes in demyelination and remyelination in an experimental model of MS [33]. It is known that pericytes participate in the functional neurovascular unit [34], being a substantial component in the development and maintenance of the stability of the blood–brain barrier (BBB). In addition, pericytes cooperate with other cells in the autoimmune reactions of the central nervous system (CNS), having the capacity to interact with oligodendrocytes and astrocytes and even to generate other cell lines. The chapter describes the ultrastructural characteristics of pericytes in EAE, concluding that novel therapeutic regimes that protect pericytes at the initial stages of demyelination may open

proper management and treatment of the disease [22].

corticosteroids and immunosuppressants [26].

promising new horizons in the treatment of MS.

pathogenetic procedure [29].

affects between 23% and 76% of the general population [19, 20]. Chapter 6 describes the various clinical and neuropathological types of diabetic neuropathies [21]. The authors emphasize the importance of the early clinical assessment of patients for proper management and treatment of the disease [22].

The vascular factor is an additional component in the broad pathogenetic background of central and peripheral demyelination. Anti-neutrophil cytoplasmic antibodies (ANCAs) may induce necrotizing vasculitis, which has polymorphic symptomatology including peripheral neuropathy in 50% of cases [23, 24]. In Chapter 7 [25] discusses the prevalence, clinical manifestations, prognosis, and treatment of peripheral neuropathies due to ANCAs, underlining that mononeuritis multiplex is the most common clinical form of peripheral neuropathy in antibodies-associated vasculitides (AAV), necessitating prompt treatment with corticosteroids and immunosuppressants [26].

The mechanical lesions of the peripheral nerves are not a rare phenomenon. Compression on peripheral nerves may provoke serious functional deficits, particularly whenever it occurs for a long time at certain points along the nerves' anatomical pathways [27]. In Chapter 8, [28] the authors discuss the many types of entrapment neuropathies concerning the upper extremities. The authors present a detailed schematic topographic analysis of the vulnerable points of the nerves along their course. In addition, they offer a precise description of the clinical signs of diagnostic significance in each one of the syndromes of entrapment neuropathies, highlighting the substantial role that anatomical variations, trauma, metabolic diseases, tumors, synovitis, and vitamin B6 deficiency play, among others, in their pathogenetic procedure [29].

The main doctrine in medicine based on the Hippocratic aphorism οφελέειν ή μη βλάπτειν is the alleviation of human suffering and the improvement of the quality of life of patients. For the realization of this doctrine, according to Galen, experimental research is essential for further understanding of the pathogenetic mechanisms of diseases and subsequent tracing of new proper and efficient therapeutic approaches. In the field of demyelinating diseases, the development of experimental models of demyelination and remyelination in vitro and in vivo is a necessity [30]. Given that MS has a dominant place in the spectrum of demyelinating disorders, several models of experimental encephalomyelitis have been introduced, approximating the clinical and neuropathological phenomena of the disease [31]. Many of those models, such as experimental autoimmune encephalomyelitis (EAE), toxic, viral, and transgenic models, are described in Chapter 9 [32], which emphasize the value of understanding MS via patient data.

Finally, Chapter 10 discusses the role of pericytes in demyelination and remyelination in an experimental model of MS [33]. It is known that pericytes participate in the functional neurovascular unit [34], being a substantial component in the development and maintenance of the stability of the blood–brain barrier (BBB). In addition, pericytes cooperate with other cells in the autoimmune reactions of the central nervous system (CNS), having the capacity to interact with oligodendrocytes and astrocytes and even to generate other cell lines. The chapter describes the ultrastructural characteristics of pericytes in EAE, concluding that novel therapeutic regimes that protect pericytes at the initial stages of demyelination may open promising new horizons in the treatment of MS.

The editors wish to extend their gratitude to the authors for their valuable contributions as well as to the staff at IntechOpen for their assistance throughout the publication process.


*Article* **Optimization of Collagenase Production by** *Pseudoalteromonas* **sp. SJN2 and Application of Collagenases in the Preparation of Antioxidative Hydrolysates**

**Xinghao Yang 1,2,†, Xiao Xiao 1,†, Dan Liu 1, Ribang Wu 1, Cuiling Wu 1, Jiang Zhang 1, Jiafeng Huang 1, Binqiang Liao 1 and Hailun He 1,\***

Received: 18 October 2017; Accepted: 29 November 2017; Published: 4 December 2017

**Abstract:** Collagenases are the most important group of commercially-produced enzymes. However, even though biological resources are abundant in the sea, very few of these commercially popular enzymes are from marine sources, especially from marine bacteria. We optimized the production of marine collagenases by *Pseudoalteromonas* sp. SJN2 and investigated the antioxidant activities of the hydrolysates. Media components and culture conditions associated with marine collagenase production by *Pseudoalteromonas* sp. SJN2 were optimized by statistical methods, namely Plackett–Burman design and response surface methodology (RSM). Furthermore, the marine collagenases produced by *Pseudoalteromonas* sp. SJN2 were seen to efficiently hydrolyze marine collagens extracted from fish by-products, and remarkable antioxidant capacities of the enzymatic hydrolysates were shown by DPPH radical scavenging and oxygen radical absorbance capacity (ORAC) tests. The final optimized fermentation conditions were as follows: soybean powder, 34.23 g·L−1; culture time, 3.72 d; and temperature, 17.32 ◦C. Under the optimal fermentation conditions, the experimental collagenase yield obtained was 322.58 ± 9.61 U·mL−1, which was in agreement with the predicted yield of 306.68 U·mL−1. Collagen from Spanish mackerel bone, seabream scale and octopus flesh also showed higher DPPH radical scavenging rates and ORAC values after hydrolysis by the collagenase. This study may have implications for the development and use of marine collagenases. Moreover, seafood waste containing beneficial collagen could be used to produce antioxidant peptides by proteolysis.

**Keywords:** collagenase; fermentation optimization; collagen; *Pseudoalteromonas*; antioxidant peptides