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JOURNAL OF ADVANCED DIELECTRICS

Vol. 5, No. 3 (2015) 1550021 (10 pages)


© The Author(s)
DOI: 10.1142/S2010135X15500216

Dielectric properties of human diabetic blood: Thermodynamic characterization


and new prospective for alternative diagnostic techniques
F. Farsaci*, S. Ficarra†, A. Russo†, A. Galtieri† and E. Tellone†,‡
*IPCF-C.N.R., Via Ferdinando Stagno d'Alcontres 37
98158 Faro Superiore, Messina, Italy
and
†Department of Chemical Sciences
University of Messina, Viale Ferdinando Stagno
d'Alcontres 31, 98166 Messina, Italy
‡etellone@unime.it

Received 12 March 2015; Revised 9 April 2015; Accepted 9 June 2015; Published 2 July 2015
In this paper, we will show the possibility of studying physical properties and irreversible phenomena that occur in blood by
applying the dielectric Kluitenberg's nonequilibrium thermodynamic theory. Namely, we shall use some recent extensions of this
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

theory that allow to infer its main characteristic parameters from experimental measures. Applying these results to the study of
normal and diabetic blood we show, by comparing them, that it is possible to determine the difference, in some details, of the
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amount of particular phenomena occurring inside them and give a biological meaning to these phenomena. Moreover, observing a
correspondence between a particular value of the frequency for which state coefficients are equal and glucose levels we introduce an
alternative diagnostic method to measure the values of the glucose in the blood by determining only this frequency value. The
thermodynamic description will be completed by determining the trend of the entropy production.
Keywords: Blood; dielectric relaxation in blood; nonequilibrium thermodynamics.

1. Introduction 1.1. Dielectric properties approach


Diabetes mellitus (DM) is a group of complex multisystem The study of the dielectric properties of materials can be
metabolic disorders characterized by a relative or absolute in- approached in two ways: (i) a theoretical point of view and
sufficiency of insulin secretion and/or concomitant resistance (ii) an experimental point of view. The experimental ap-
to the metabolic action of insulin on target tissues. Diabetes is proach is fundamental because it is the first interaction with
an increasingly significant health problem as the prevalence the medium and it furnishes a quantitative and qualitative
increases with age, the lifetime risk of developing diabetes is vision of the phenomena object of study which occur in the
around 10%.1 According to the 1999 World Health Organi- medium and the evolution of these phenomena. This infor-
zation (WHO) criteria (which are also endorsed by Diabetes mation is utilized to formulate models which are in agreement
UK), diagnosis of diabetes is made if the fasting blood glucose with experimental data. Obviously for the formulation of
level is 7.0 mmol/L or more, or a random blood glucose test these models it is necessary to identify the variables which
shows a level of 11.1 mmol/L or more. People with diabetes describe the phenomena. Unfortunately, the number of vari-
have an increased risk of developing a number of serious health ables that describe a biological system is very large, so it is
problems such as coronary heart disease, blindness, kidney essential to reduce this number to formulate a concrete
failure, stroke and peripheral vascular disease.2–4 In fact, hy- model. Obviously this means substituting the real system
perglycemia, i.e., consistently high blood glucose levels easily with an ideal one whose description is limited to the chosen
can lead to serious oxidative stress due to the increased pro- variables. But, as a consequence of the complexity of bio-
duction of free radicals. The reactive oxygen and nitrogen logical phenomena, it is very difficult to identify the variables
species (ROS and RNS) through lipid peroxidation of mem- giving the best — or at least a sufficiently good — descrip-
brane are responsible for the irreversible changes in the tion. Every model will be associated to a particular choice of
structure of the red blood cell (RBC) cytoskeleton. Therefore, variables so to conceive the theoretical approach. From a
the toxic effect of glucose on erythrocytes manifests itself not dielectric point of view, well-known models are based on the
only as an alteration of the phospholipids' bilayer but also as a introduction of combination in series or in parallel of ca-
modification of the integral proteins and of the hemoglobin pacitance and conductance. We call the models based on
(Hb), protein involved in the oxygen transport, abundantly these combinations classical models. These electrical models,
expressed in the RBCs. in some cases, describe well the real biological elements and

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(CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited.

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F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

their functions; for example, it is well known that some over time, but, unlike models cited, they may depend on some
aspects of the cell membrane are well described by a ca- characteristic of the perturbation acting on the medium. In the
pacitance element.5,6 case considered by us they may depend on the frequency of
In this context, the classical models are used to determine the harmonic perturbation acting on the medium. Here, as in
dynamical constitutive differential equations for dielectric the aforementioned classical models, if the phenomenological
relaxation which describe some specific properties of the and state coefficients are known and, for example, the po-
medium under consideration. Of course, depending on the larization, it is possible by integration of the dielectric
analyzed medium, a suitable combination of capacitance and equation to obtain the behavior of electric field.
conductance can be chosen. These models are able to de- In previous papers,11–15 we approached the study of di-
scribe some dielectric relaxation phenomena in the linear electric properties of a medium by another point of view: we
approximation.7 investigated the behavior of phenomenological and state
But in the differential equations of these models appear coefficients assuming as known harmonic perturbation and
some parameters which are assumed as constant character- the response of the medium. This leads to the determination
istics of the medium. In other words, it is assumed that these of the aforementioned coefficients as function of the fre-
parameters do not depend on the type of perturbation. quency of perturbation, as aforementioned. There we have
For example, if the medium is perturbed by a harmonic taken into account the linear response theory. This will be
electric field of frequency, !, these parameters remain con- clear in the next sections where we will make a summary of
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stant for each frequency. Indeed, since these parameters the results obtained by us. Here we emphasize that the re-
characterize the medium, they must depend on the type of sponse of the medium depends on the type of perturbations.
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perturbation. Nevertheless, the assumption of the constancy We will remark that most of the classical models (related
of these parameters will be an approximation which in some to combination in series or in parallel of capacitance and
cases results in a good one. conductance) are always formulated to fit experimental data
Now, if we consider as known the parameters that appear and, if they are not in agreement with experiments, they are
in the classical differential equation, by assuming as known mathematically modified to this aim.
perturbation an extensive variable as the polarization field In this work, we do not formulate any model to fit data,
(the cause), the integration of the dielectric differential but we will study some thermodynamic irreversible processes
equation leads to the knowledge of the intensive variable of occurring inside the blood by applying some recent results on
the electric field inside the medium (effect). This approach nonequilibrium thermodynamic theory obtained by us so to
does not give information on the parameters that appear in the determine the thermodynamic function correlated to the
equation, but considering them as known, it is able to give phenomena under study. In other words, we will apply the
information on the effects (electric field) of evolution of the nonequilibrium thermodynamic approach to the study of a
medium when subject to a known perturbation. By starting biological system such as blood.7–9
from nonequilibrium thermodynamic consideration and by We are conscious of the difficulties to adapt the non-
introducing the concept of internal hidden variables associ- equilibrium thermodynamic theory (which is based also on a
ated to the internal degree of freedom, Kluitenberg obtained a model of inert matter) to the very complex phenomena that
dielectric relaxation equation that generalizes the above occur in blood. Nevertheless, we think that this new approach
mentioned classical models.8–10 can produce very important results because it provides, from
Moreover, we have proved that even fractionary models a thermodynamic point of view, new and more detailed in-
such as Cole-Cole and others will result as particular case of formation on some processes which occur inside the medium
the extended Kluitenberg's introduced by us. This has been so to determine some physical entities (the more important of
possible because Prof. Kluitenberg proved that the polariza- which is the entropy production) which can be used as di-
tion vector can be split into two parts. We have proved, in agnosis and to study the evolution of some pathologies.
previous papers,11–15 that the parameters called phenomeno- In particular, we will use this new approach to deepen the
logical and state coefficients, which appear in Kuitenberg's differences between physiological blood (pb) and diabetic
dielectric differential equation, depend on the perturbation blood (db).
and we have expressed them as a function of frequency of an Thus, the problem is the applicability of the nonequilib-
harmonic perturbation by means of the relations, obtained by rium thermodynamic to the phenomena which occur inside
us, between these parameters and some frequencies depend- system under study: the blood. In other words, can the blood
ing on moduli which can be directly measured. model that we consider satisfy the basic axiom of the non-
Moreover, a very important result of the theory is that the equilibrium thermodynamics? This will be the subject of the
so-called phenomenological and state coefficients are corre- next section in which we introduce a blood model and
lated to single phenomena (here we will refer only to di- compare it with the basic axioms on local and instantaneous
electric media of order one). So we can identify each equilibrium of the thermodynamic of irreversible processes.
coefficient just to one phenomenon. Also in this approach it is Unfortunately our results do not have any direct experi-
assumed that the aforementioned coefficients are constant mental confirmation, because they consist to obtain the

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F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

expression of some fundamental thermodynamic entities as In the pathology of DM, the presence of additional glu-
functions of the frequency of perturbation. In particular, we cose in the blood alters the physical-chemical properties of
obtained the following results: the blood such as the electric and dielectric properties.16–19 A
comparative study of the electrical properties of healthy and
1. analytical expression of the polarization vector (P ð0Þ ,
pathological blood can lead to a better understanding of bi-
P ð1Þ Þ.
ological processes linked to diabetes and to the discovery of
2. analytical expression of the state coefficients a ð0;0Þ , a ð1;1Þ
new methods for early diagnosis. One of the main alterations
characteristic of the medium.
that occur in the blood in the presence of high glucose con-
3. analytical expression of coefficients L ð1;1Þ and L ð0;0Þ re-
centrations (diabetes disorders) is the glycosylation of pro-
lated to irreversible processes due to the displacement
teins. Glycosylation refers to the covalent bonding of glucose
current associated to temporal variation of part of polar-
to the blood proteins, in fact, glucose is chemically reactive
ization P ð1Þ and to temporal variation of vector P, re-
and has a slight reducing capacity to accept electrons from the
spectively.
"-amino group of a protein lysine residue, to form an adduct
4. analytical expression of electric field E ð1Þ related to
commonly referred to as a Schiff base. Lysine is found in
temporal variation of part of polarization P ð1Þ .
virtually every protein and when that electron is shared it
5. analytical expression of entropy production.
creates an irreversible chemical bond between the glucose
No results of this kind exist in literature. and the protein. Glycosylation can also occur at the N-ter-
minal amino group of the -chains by a ketoamine linkage.
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

This is the case of the mainly glycosylated protein in blood,


1.2. Mathematical model of the blood and basic axiom
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the HbA1c is the result of nonenzymatic reaction of glucose


Human blood accounts for 7% of the body weight, its main with the -amino groups of the Valine residues at the N-
roles in the organisms are: it carries the nutrients and mo- terminus of Hb -chains.20 Normally, only a small percentage
lecular oxygen indispensable to the cellular metabolism and of blood glucose, usually between 4.5% and 6%, is cova-
at same time it has an important thermoregulatory role. From lently linked to the Hb of nondiabetes population. But, under
the electrical point of view, human blood is a very inhomo- conditions of sustained hyperglycemia such as DM, a sig-
geneous solution composed of plasma and several kinds of nificant increase in the percentage of glycosylated Hb is
cells; these cells called corpuscles or \formed elements" commonly noted: HbA1c is increased two- to three-fold in
consist of erythrocytes (RBCs), leukocytes (white blood cells, the RBCs. Nevertheless the increased amount and perma-
WBCs) and thrombocytes (platelets). By volume, the RBCs nence of glucose in the blood allows more glycosylation to
constitute about 45% of whole blood, the plasma about occur, not only with Hb, but with the proteins of the eryth-
54.3% and WBCs about 0.7%. rocyte membrane and with other proteins of the plasma. The
RBCs are biconcave disk shaped and small size (7 m); binding of glucose, especially with important protein amino
they are highly specialized cells providing as much space for groups, can affect cell structure and function and create an
Hb (4–5 mM) as possible, in fact they have no nucleus, unbalance which leads to cell destabilization. Because, each
mitochondria or endoplasmic reticulum. Hb is a globular of these proteins can undergo cyclization and rearrangement
protein, the main function of which is to transport oxygen or cross linking to create something called advanced glyco-
from lungs to respiring tissues. WBCs differ from RBCs sylation end products (AGEs).21
because they always have a nucleus and their shape is usu- Our approach is based on the assumption (supported by
ally spherical. There are two main groups of WBCs: pha- experiments) that in biological tissue hidden electrical phe-
gocytes and lymphocytes. Phagocytes which destroy nomena occur to which corresponding internal degree of
invading cells by phagocytosis are characterized by lobed freedom must be taken into account for a more detailed de-
nuclei and granular cytoplasm. Lymphocytes that destroy scription and prediction.
microorganisms secreting antibodies are smaller than pha- So we consider blood as a conducting fluid in which three
gocytes and are recognized by large nucleus. In the blood of major micro-particles are suspended (RBCs, WBCs, MLPs)
all vertebrates, the plasma mostly water contains a wide and distributed in an homogeneous way.5,6,22
variety of substances such as proteins, cholesterol, hor- This allows us to consider blood as a continuum medium
mones, amino acids, glucose, salts, vitamins and antibodies. which obeys the continuum mechanics indefinite equations
Among these an important role is carried out by the glucose and Maxwell's equation in the matter with a mass density 
sugar, selected as central carbohydrate for its functions both which varies as a function of blood's elements under con-
metabolic and structural. Its normal concentration is regu- sideration.23 In Sec. 2.3, where we describe in a synthetic
lated by several hormones but in some metabolic disorders as form our theory, we will prove that, by considering blood as
well as those present in diabetes, glucose concentration in an incompressible fluid, the Lagrangian's derivative d dt of the
the blood can reach toxic levels responsible for the func- mass density results in zero. In other words, we will prove
tional and structural alterations of the cell constituting the that the mass density is almost constant for each fluid element
hematic tissue. during the motion. This is justified if we consider the mass

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F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

density of three major micro-particles of blood (as RBCs, By assuming that exists a state R at the constant temper-
WBCs, MLPs). ature T0 in which it results:
Such an assumption is also in agreement with the basic
ðeqÞ ðeqÞ
axiom on local and instantaneous equilibrium: for sufficiently  ik ðT0 Þ ¼  ikð0Þ ¼ 0;
small deviation from equilibrium, a system can be divided
ðeqÞ
into tiny (physical) volume elements, each of which can be E ðeqÞ ðT0 Þ ¼ E ð0Þ ¼ 0
regarded as a small homogeneous equilibrium system.
Moreover, the length and time scale of these subsystems it can be shown that the polarization p is additively composed
are infinitesimally small from a macroscopic point of view, of two parts p ð0Þ and p ð1Þ
but from a molecular point of view they are still large, such
p ¼ p ð0Þ þ p ð1Þ ; ð2bÞ
that the subsystem contains enough molecules so that the
average taken on the number of molecules has deterministic where following the Debye's model, the vector p ð0Þ is asso-
significance. ciated with molecule deformation polarization and p ð1Þ is
Since we will study blood when it is subject to an external associated with molecule rotation polarization.
harmonic electric perturbation we assume that in this case Moreover, it can be shown that the change of both p ð0Þ
the axiom of local and instantaneous equilibrium will and p ð1Þ contributes to entropy production and therefore they
be satisfied; this is true for a sufficiently low intensity represent two irreversible processes. With these clarifications,
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

perturbation. Eq. (2a) can be written as:


s ¼ sðuj"ik jpjp ð1Þ Þ ð3Þ
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2. Methods and introduction of vector E ðirÞ defined as:


2.1. Theoretical thermodynamic approach
E ðirÞ ¼ E  E ðeqÞ ð4Þ
Kluitenberg's theory is based on the idea that the usual
is possible, where E is the electric field which occurs in
variables of nonequilibrium thermodynamic are insufficient
Maxwell's equations and E ðirÞ is called the irreversible elec-
to describe some phenomena that occur in a medium when it
tric field. If the irreversible electric field (4) vanishes the
is subject to perturbation. In particular, they are insufficient to
change in p ð0Þ does not contribute to the entropy production,
describe relaxation dielectric phenomena in a continuous
i.e., changes in p ð0Þ are reversible processes.10
media (we neglect the magnetic effects).
Generally it is assumed that the specific entropy s of an
elastic dielectric is a function of the specific internal energy u, 2.2. Phenomenological equations
the strain tensor "ik and the specific polarization p 8–10:
The entropy production per unit of volume and per unit of
s ¼ sðuj"ik jpÞ: ð1Þ time is given by10
 ðsÞ ¼ J ðQÞ  X ðQÞ þ J ðelÞ E
The new Kluitenberg's idea consists in the assumption
dp dp ð1Þ
that there is a vector field
which plays the role of ther- þ E ðirÞ þ E ð1Þ ; ð5Þ
modynamic internal degree of freedom and which influences dt dt
the polarization.8–10 In the theory it is assumed that the where J ðQÞ is the heat flow and J ðelÞ is the density of electric
specific entropy (which we indicate with s) has the following current;
functional dependence
X ðQÞ ¼ T 1 gradT:
s ¼ sðuj"ik jpj
Þ: ð2aÞ
It appears that the entropy production (5) is due to heat
From which it follows: conduction, electric conduction and dielectric relaxation.
8 Moreover, it is a sum of inner products of vectors.
>
> 1 @sðuj"ik jpjp ð1Þ Þ
> ¼
> ; In agreement with the method of nonequilibrium ther-
>
> T @u
>
> modynamics developed by De Groot e Mazur (see Ref. 7),
>
> @sðuj"ik jpjp ð1Þ Þ
>
> ðeqÞ there will be linear relations among these quantities which,
>
< ik ¼ T ;
"ik for an isotropic media, can be written as:
>
> @sðuj"ik jpjp ð1Þ Þ dp
>
> E ðeqÞ ¼ T ; E ðirÞ ¼ L ð0;0Þ þ L ð0;1Þ E ð1Þ ; ð6Þ
>
> @p
>
> dt
>
>
>
> @sðuj"ik jpjp ð1Þ Þ dp ð1Þ dp
>
: E ð1Þ ¼ T :  ¼ L ð1;0Þ þ L ð1;1Þ E ð1Þ ; ð7Þ
@p ð1Þ dt dt

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F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

where L ð0:0Þ ; L ð0:1Þ ; L ð1:0Þ ; L ð1:1Þ ; L ð0;1Þ ; L ð1;0Þ are phenome- which together with Eqs. (6) and (7), in which we neglect the
nological coefficients and we shall assume that they are cross effects which may occur between them,
constant in time. The coefficients L ð0:1Þ ; L ð1:0Þ are connected dP
with possible cross effects which may occur between the two E ðirÞ ¼ L ð0;0Þ ; ð13Þ
dt
types of dielectric relaxation phenomena described by
Eqs. (6) and (7), and they satisfy the Onsager–Casimir re- dP ð1Þ
¼ L ð1;1Þ E ð1Þ
ciprocal relations dt
¼ L ð1;1Þ ½E ðeqÞ þ ða ð0;0Þ  a ð1;1Þ ÞP ð1Þ  ð14Þ
L ð0:1Þ ¼ L ð1:0Þ :
will be the equations that allow us to the introduction of
If we neglect the cross effect described by coefficients L ð0:1Þ relaxation equation.
and L ð1:0Þ we observe that, the coefficient L ð0:0Þ , which has the As aforementioned now we prove that for a fluid as blood
dimension of a resistance, is connected to irreversible pro- it is reasonable to assume that  is constant for each element
cesses related to change of p (and therefore of p ð0Þ , p ð1Þ or so to verify the basic axioms on local and instantaneous
both p ð0Þ and p ð1Þ , while L ð1:1Þ , which has the dimension of a equilibrium.
conductibility, is related to change of p ð1Þ and the corre- In fact, the assumption that the blood is an incompressible
sponding intensive variable E ð1Þ . However, Eqs. (6) and (7) fluid is expressed for a fluid's element d by mathematical
are connected with irreversible changes in the polarization. relation dtd ðdÞ ¼ 0; so, from the well-known cinematic re-
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

lation dtd ðdÞ ¼ divV d, it follows divV ¼ 0. This last


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2.3. Linear approximation state equations equation and the equation of conservation of the mass d dt þ
divV ¼ 0 lead to assert that.
The free energy f is defined by
d @
f ¼ u  Ts: ¼ þ V  grad ¼ 0: ð15Þ
dt @t
Here V is the velocity of the fluid element. If the fluid is not
It can be shown that there exists the following functional
homogenous at the initial instant its initial density 0 varies
dependence of f:
with Lagrangian' coordinates (b1 , b2 , b3 Þ so as to have
f ¼ f ðTj"ik jpjp ð1Þ Þ: 0 ¼ 0 ðb1 ; b2 ; b3 Þ:
By substituting the following relation (which is valid during
This is the specific free energy and it can be shown8–10 the motion) bi ¼ bi ðt; x1 ; x2 ; x3 Þ in the last equation, one has
that the condition of isotropy and of linearity of equations of
state are fulfilled if it is assumed that f is the sum of two 0 ðb1 ; b2 ; b3 Þ ¼ 0 ½bi ðt; xi Þ ¼ ðt; x1 ; x2 ; x3 Þ:
functions f1 and f2 This relation satisfy Eq. (15) and proves the assert.
f ¼ f1 þ f2 ; Thus we assume that the mass density  is constant.8–10 It
is seen from Eq. (14) that sudden change in P ð1Þ is impos-
where sible, while from Eq. (13) it follows that sudden change in
P ð0Þ is possible.
f1 ¼ f1 ðTj"ik Þ; ð8Þ
1 2
f2 ¼ ½a ð0;0Þ p  ðp  2p ð1Þ Þ þ a ð1;1Þ p ð1Þ ; ð9Þ 2.4. Relaxation equation
2
In the following, we assume that T ¼ constant, in agreement
where a ð0;0Þ and a ð1;1Þ are state coefficients (assumed con- with blood status. It can be shown that it is possible to
stant) which have the dimension of reciprocal dielectric eliminate the internal fields and the two fields P ð0Þ and P ð1Þ
constant. from Eqs. (11)–(14) so to obtain the so-called relaxation
By defining the fields P ð0Þ and P ð1Þ by equation, mentioned in Sec. 1:
P ð0Þ ¼ p ð0Þ ; ð0Þ dE ð0Þ ð1Þ dP
2
ð2Þ d P
 EP E þ ¼  PE P þ  PE þ  PE 2 ; ð16Þ
ð1Þ ð1Þ
P ¼ p ; ð10Þ dt dt dt
where
P ¼ P ð0Þ þ P ð1Þ ;
ð0Þ
we can obtain from equation, the following state equations  EP ¼ a ð1;1Þ L ð1;1Þ ; ð17Þ
ð0Þ
E ðeqÞ ¼ a ð0;0Þ ðP  P ð1Þ Þ ¼ a ð0;0Þ P ð0Þ ; ð11Þ  PE ¼ a ð0;0Þ ða ð1;1Þ  a ð0;0Þ ÞL ð1;1Þ ; ð18Þ
ð1Þ
E ð1Þ ¼ a ð0;0Þ P  a ð1;1Þ P ð1Þ ; ð12Þ  PE ¼ a ð0;0Þ þ a ð1;1Þ L ð0;0Þ L ð1;1Þ ; ð19Þ

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F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

ð2Þ
 PE ¼ L ð0;0Þ : ð20Þ time. Here, we introduced a new quantity defined as:
Moreover it can be shown that phenomenological and ð1Þ
ð0Þ ð0Þ ð1Þ ð2Þ ¼ 2  !L ð0;0Þ : ð27Þ
state coefficients together with  EP ,  PE ,  PE ,  PE must be 2

positive in order to satisfy the principle of entropy produc- By remembering the meaning of 2 ,24 the last equation
tion. Moreover, the following relations must be satisfied: represent the difference between the total loss modulus and
ð1Þ ð0Þ ð2Þ the loss associated to E ðirÞ (then E ðirÞ and L ð00Þ are not related
 PE   EP  PE > 0;
to internal degree of freedom); in other words Eq. (27)
ð1Þ ð0Þ ð0Þ
 PE  EP   PE  0: represents the dissipation associated to internal degree of
freedom.
The importance of the phenomenological and state coef- ð1Þ
From (22) and (24), it follows that, if 2 ¼ 0, no dissi-
ficients is that they characterize the medium specifying the
pation is connected to internal degree of freedom, it follows:
amount of type of phenomena correlating to each of them.
It is important to observe that their constancy is referred to a ð0;0Þ ð!Þ ¼ 1; ð28Þ
the time for each type of perturbation which acts on the
medium. But they vary with the change of perturbation. L ð1;1Þ ¼ 0: ð29Þ
For example, if the perturbation is of harmonic type
with frequency ! then the coefficients will depend on ! (we And from (14) and (24) it follows
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

will see this in next section) which can be considered as


parameter in the functional dependence of the coefficients. In P ð1Þ ¼ cost: ¼ 0: ð30aÞ
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this case, we shall call a ð0;0Þ ; a ð1;1Þ ; L ð0;0Þ ; L ð1;1Þ dynamical We observe that 2 ¼ if !L ð00Þ
¼
ð1Þ
¼ 0); this 0ðL ð11Þ
2
coefficients. occurs for sufficiently low frequency where the internal de-
gree of freedom does not appear. So we can put15
2.5. Phenomenological and state coefficients 2 ðlow frequencyÞ ¼ 2R ¼ !L ð0;0Þ ð30bÞ
as function of frequency
In the following, we consider the vector component normal to
the surface of the electrode, the latter being on the surface of 2.6. Evaluation of the fields E (eq) , E (1) E (ir) , P (0) , P (1)
blood. Assuming that P varies as
Now we will evaluate the fields E ðeqÞ , E ð1Þ E ðirÞ , P ð0Þ , P ð1Þ
P ¼ P0 sin !t ð21Þ taking into account Eqs. (22)–(25). This allows us an ex-
and by introducing some appropriate approximations, phe- perimental evaluation of these fields since are known by
nomenological and state coefficients can be expressed as experimental measurements coefficients (22)–(25).
functions of the frequency as follows15,23: We introduce the normal component of E ðeqÞ , E ð1Þ E ðirÞ ,
P , P ð1Þ which we will indicate as E ðeqÞ , E ð1Þ E ðirÞ , P ð0Þ , P ð1Þ .
ð0Þ
ð1Þ
In agreement with linear response theory,23,24 we assume
a ð0;0Þ ð!Þ ¼ 1þ
2
; ð22Þ
! that P varies as Eq. (21), and that E varies as
ð1Þ
½ 2 þ 1 !
2 E ¼ E0 ð!Þ sinð!t þ ð!ÞÞ ð31Þ
a ð1;1Þ ð!Þ ¼ ð1Þ
; ð23Þ
! 2 ð1 þ ! 2 2Þ or
ð1Þ
! 2 ð1 þ !  Þ
2 2 E ¼ P0 1 sin !t þ P0 2 cos !t; ð32Þ
L ð1;1Þ ð!Þ ¼ ð1Þ
; ð24Þ
½ 2 þ 1 !
2
where
8
> E0 ð!Þ
L ð0;0Þ ð!Þ ¼ 2R
; ð25Þ >
< ¼ cos ð!Þ;
! 1
P0
ð33Þ
where >
> E ð!Þ
: 2 ¼ 0 sin ð!Þ:
"1  "0 P0
1 ¼ ; ð26Þ
ð"1  "0 Þ 2 þ " 22 ð!Þ is the phase lag between P and E. From this it follows
"2 that the relaxed value 1R obtained for ! ¼ !R will be
2 ¼
ð"1  "0 Þ 2 þ " 22 E0R
1R ¼ ; ð34Þ
and 2R is the relaxed value for ! ¼ !R. Here !R is the 24 P0
frequency under which 2 is almost constant.
where
Here "1 and "2 are real and imaginary parts, respectively,
of the complex dielectric constant and  is the relaxation E0R ¼ Eð! ¼ !R Þ: ð35Þ

1550021-6
F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

Combining (33) and (34) it follows 3. Results and Conclusions

E0R Here we will refer to experimental data obtained by Abdalla


1 1
E0 ð!Þ ¼ P0 ¼ : ð36Þ et al.5 for complex dielectric constant of the pb and db. We
cos ð!Þ cos ð!Þ 1R
use these data for calculation of thermodynamic functions of
Now we are able to obtain an explicit form of the the theory and we analyze the results obtained following the
aforementioned fields which is suitable for experimental Debye's point of view8–10 according to which it is assumed
evaluation. that for molecule deformation polarization is associated with
From Eqs. (13) and (21) it follows: vector P ð0Þ and for molecule rotation polarization is associ-
ated with P ð1Þ . Obviously, for each molecule both phenomena
dP E may be present.
E ðirÞ ¼ L ð0;0Þ ¼ L ð0;0Þ 0R ! cos !t: ð37Þ Here as aforementioned, we consider only the component
dt 1R
of the vector that is normal to the surface plate, so we write
ð0Þ ð1Þ
From (32), (36) and (37) it follows P ð0Þ , P ð1Þ for pb and P d , P d for db. In general, we will
indicate with an index \d" the function referred to db.
E¼ 1P þ 2
E ðirÞ : ð38Þ We start by analyzing the behavior of P ð0Þ both for pb and
L ð0;0Þ !
for db. By observing Fig. 1 we note that by increasing fre-
ð0Þ
This equation is similar to Eq. (4). They can be equated if quency it results always in P ð0Þ > P d . This means that in pb
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

we have a greater number of dipoles that follow the pertur-


2 is connected only with irreversible dielectric relaxation
phenomena, since in general it is the synthesis of many dis- bation field than in db. From a biochemical point of view we
by 200.132.111.137 on 03/07/18. For personal use only.

sipative phenomena which occur inside the medium. We explain this by observing that excess glucose in db will lead
impose this equality assuming for 2 the value 2 ð!R Þ ¼ 2R to generation of chemical bonds between blood elements
for low (and high) frequency which we consider as the \best and sugar.
representation" of the aforementioned phenomena (in anal- In this context, the glycosylation of proteins may be the
ogy with mechanical case). In this case we have: cause of reduced movement of elongation. In fact, glucose
reacting nonenzymatically with proteins to form stable co-
E ðeqÞ ¼ 1 P; ð39Þ valent linkages increases the molecular weight of glycated
proteins.25 Besides, further increases in blood sugar lead to
L ð0;0Þ ¼ 2R
: ð40Þ further glycation of proteins and lipids with molecular rear-
! rangements that lead to generation of AGEs.
From (11) and (39) it follows Other intracellular and membrane proteins of RBCs are
also glycated, for example Spectrin, a major RBC membrane
E ðeqÞ 1P
P ð0Þ ¼ ð0;0Þ
¼ ð0;0Þ ; ð41Þ protein, band 3 transmembrane protein, and band 4–1. The
a a
glycation results in reduced RBC deformability and in an
where a ð00Þ is given by Eq. (22). increased adherence to endothelium. Platelet membrane
From (2b), (21) and (41) it follows: proteins can be glycated. The increased binding of fibrinogen
  and the increased platelet aggregation observed in diabetic
ð1Þ ð0Þ 1
P ¼PP ¼P 1 : ð42Þ patients26 can be related to glycation of the adenosine di-
a ð0;0Þ
phosphate receptors and lipids indicating that the number of
By taking into account (14) and (42) one has:
  0 1x107 2x107 3x107
1 dP ð1Þ P0 ! cos !t
E ð1Þ ¼ ð1;1Þ ¼ 1  1
: ð43Þ P(0)
L dt L ð1;1Þ a ð0;0Þ 1,0x100 1,0x100
P(1)
The entropy production (5) in the case of only dielectric P(0)
8,0x10-1 d 8,0x10-1
relaxation phenomena becomes: P(1)
d P (0)

 ð1Þ
 6,0x10-1 P(0)
d 6,0x10-1
ðsÞ 1 ðirÞ dp ð1Þ dp
 ¼T E þE ; ð44Þ
P(0)

dt dt 4,0x10-1 P(1) 4,0x10-1


d

where heat flow and density of electric current have been P(1)
2,0x10-1 2,0x10-1
neglected.
Taking into account Eqs. (21), (30b), (42) and (43) one 0,0 0,0
has:
! 0 1x107 2x107 3x107
ð1Þ
ðsÞ P 20 ð0;0Þ ω
 ¼ !L þ 2
!cos 2 !t: ð45Þ
T ð1 þ ! 2  2 Þ
Fig. 1. P ð0Þ and P ð1Þ for pb and db (Eq. (42)).

1550021-7
F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

0 1x107 2x107 Here we will emphasize that, even if we can separate,


normal both deformation and rotation of polarization are present in
normal normal each blood element as it is shown by Eq. (12) if we rewrite it
diabetic in the form:
diabetic
a(0,0) E ð1Þ ¼ a ð0;0Þ P ð0Þ þ ða ð0;0Þ  a ð1;1Þ ÞP ð1Þ ¼ E ðeqÞ þ E xð1Þ ;
107 107 ð46Þ
a(0,0),a(1,1)

(0,0)
a
d
where
E xð1Þ ¼ ða ð0;0Þ  a ð1;1Þ ÞP ð1Þ ð47Þ
(1,1)
a

diabetic a(1,1) is the field associated only to rotation polarization of the per-
manent dipoles represented by P ð1Þ. From Eq. (46) we can
d

deduce that the field E ð1Þ is sum of two contributes: E ðeqÞ as-
ð1Þ
0 1x107 2x107 sociated only to P ð0Þ (see Eq. (39)) and E x associated only to
ð1Þ
P (see Eq. (47)). In other words, while to the generation of
ω
the field E ðeqÞ contributes only the polarization for deforma-
Fig. 2. State coefficients for pb and db (Eqs. (22) and (23)). tion, to the generation of the field E ð1Þ contributes both the
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

polarization for deformation and for orientation (see Eq. (46)).


ð1Þ
As for E ðeqÞ we can analyze the field E x associated only to
by 200.132.111.137 on 03/07/18. For personal use only.

dipoles that follows the field is larger when the frequency ð1Þ
polarization P for both pb and db; by observing Fig. 3 we
increases. In other words, we have a new generation of po- note that there exists a frequency in which it results:
larization dipoles when frequency increases. Obviously the
field E ðeqÞ ¼ a ð0;0Þ P ð0Þ (see Eq. (11)) will be an increasing E xð1Þ ¼ E ð1Þ  E ðeqÞ ¼ ða ð0;0Þ  a ð1;1Þ ÞP ð1Þ ¼ 0
function, as confirmed by Fig. 4, since this occurs for the for both pb and db. This does not means that P ð1Þ ¼ 0ðP ð1Þ is
coefficient a ð0;0Þ (see Fig. 2): the blood will be structured in never zero, see Fig. 1) but that a ð0;0Þ ¼ a ð1;1Þ as it is shown by
such a way that in every point the field associated to polari- Fig. 2. In fact, at the same frequency in which it results
zation P ð0Þ (for deformation) will increase. By invoking the ð1Þ
E x ¼ 0 we have a ð0;0Þ ¼ a ð1;1Þ . This is true for both pb and
ð0Þ
same motivation used for explaining P ð0Þ > P d it is easy to db, so we may write:
ðeqÞ
explain the relation E ðeqÞ > E d . ð1Þ
Now we analyze the polarization P ð1Þ . On contrary to P ð0Þ E x ¼ ða ð0;0Þ  a ð1;1Þ ÞP ð1Þ ¼ 0 ) a ð0;0Þ  a ð1;1Þ ¼ 0
ð1Þ ð1Þ
it results in P d > P ð1Þ as shown in Fig. 1 and moreover P d , for ! ¼ !x ;
ð1Þ ð0;0Þ ð1;1Þ ð1Þ ð0;0Þ ð1;1Þ
P ð1Þ are decreasing functions of the perturbation frequency. E xd ¼ ða d  ad ÞP d ¼ 0 ) a d  ad ¼ 0
By invoking the meaning associated to P ð1Þ we can assert that for ! ¼ !xd :
when the perturbation frequency increases we have a lower
This is shown in Figs. 2 and 3. It is easy to show that from
number of permanent dipoles that follow the perturbation ð1Þ
ð1Þ Eqs. (22) and (23) it results a ð0;0Þ ¼ a ð1;1Þ if 2 ! ¼ 1 .
field. From a biochemical point of view we explain that P d
We note that (see Figs. 2 and 3) it results
> P ð1Þ by observing that the glucose bonding with the blood
elements will form a greater number of permanent dipoles !x > !xd :
with respect to pb. In particular, as a result of nonenzymatic
glycosylation a bulky glycogroup is introduced onto a free 0 1x107 2x107 3x107
4,0x106 4,0x106
amino group leading to a change in the isoelectric point (pI)
of the proteins. The alteration in pI will be more pronounced E(1)-E(eq)
2,0x106 2,0x106
if the sugar is phosphorylated. In fact, as it is known, the E(1)
d
-E(eq)
d

glucose within the cell is immediately phosphorylated by the


0,0 0,0
action of the kinase. The latter, having a low KM for the
E(1)-E(eq)

substrate catalyzes the reaction that leads to the formation of


the sugar phosphoric ester. In this way, in addition to neu- -2,0x106 -2,0x106

tralization of positive charge on " NH þ 3 of Lys (glycosyla-


tion), two negative charges are added on the protein due to -4,0x106 -4,0x106

ionization of phosphate linked to carbon 6 of glucose. This


change in electric charge of protein may facilitate oscillation -6,0x106 -6,0x106
0 1x107 2x107 3x107
in the field. Not to be neglected is also that all the Lys resi-
ω
dues of proteins are susceptible to glycosylation and that the
variation of electric charge is proportional to the number of Fig. 3. Field associated only to rotation polarization for pb and db
Lys characterizing each protein. (Eq. (46)).

1550021-8
F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

0,0 5,0x106 1,0x107 1,5x107 2,0x107 2,5x107 3,0x107 0 1x107 2x107 3x107
1,6x107 1,6x107

1,4x107 E(eq) 1,4x107


3x107 3x107
7 E(1)
1,2x10 1,2x107
E(eq) E(1)
d E(eq)
1,0x107 E(1) 1,0x107
d (dP(1)/dt)d
2x107 2x107
8,0x106 8,0x106
E(eq), E(1)

E(1)

dP(1)/dt
6,0x106 d 6,0x106
E(eq)
d
4,0x106 4,0x106 1x107 dP(1)/dt 1x107
6 6
2,0x10 2,0x10

0,0 0,0
0 0
-2,0x106 -2,0x106
6 7 7 7 7
0,0 5,0x10 1,0x10 1,5x10 2,0x10 2,5x10 3,0x107

ω 0 1x107 2x107 3x107

ω
Fig. 4. E ðeqÞ and E ð1Þ electric field for pb and db (Eqs. (11)
and (12)). Fig. 6. Displacement current associated to rotation polarization for
pb and db (Eq. (43)).
J. Adv. Dielect. 2015.05. Downloaded from www.worldscientific.com

This is a very important result: the existence of a fre-


ð1Þ
quency in which it results E x ¼ 0 or a ð0;0Þ ¼ a ð1;1Þ is, in
As regards the displacement current dP ð1Þ =dt associated to
by 200.132.111.137 on 03/07/18. For personal use only.

general, a peculiarity of blood, but we observe that in this


case frequency depends on the level of glucose in blood. In rotation polarization, we note in Figs. 6 and 7 that they show
particular, glucose and !xd values are linked by an inverse an increment trend for both db and pb with greater values for
correlation. This correspondence between frequency and db with respect to pb. In other words, a temporal change in
glucose level may be utilized as an alternative diagnostic P ð1Þ will result greater in db than in pb. This means that some
method to measure the values of sugar in blood. In fact, the molecules in db have a greater speed of oscillation then in the
glucose concentration is easily obtained determining the pb. We may explain this by assuming a greater polarity in db
value of frequency for which a ð0;0Þ ¼ a ð1;1Þ . (see Fig. 1).
By observing Fig. 4 we note that Examining the entropy production we note that over a
frequency (see Fig. 8), which we indicate with !s ffi 10 7 Hz,
for ! < !x it results E ðeqÞ > E ð1Þ the entropy production will result greater in pb than in db.
and for ! > !x it results E ðeqÞ < E ð1Þ ; ðsÞ
 d >  ðsÞ if ! < !s ;
i.e., the difference  E ð1Þ E ðeqÞ
changes the sign in !x . The ðsÞ
 d <  ðsÞ if ! > !s :
frequency !x is very important because it is a ring of union
between two states of blood (diabetic or not), unfortunately This means that up to frequency !s the pb is more ordered
we are not still able to give a biological explication of this with respect to db. Over this frequency the contrary occurs. It
change. This change is well represented by Eq. (46) and it is is to note (see Figs. 1 and 8) that at the frequency !s the
shown in Fig. 5.
0,0 5,0x10 6 1,0x10 7 1,5x10 7 2,0x10 7 2,5x10 7 3,0x10 7
4x10 0 4x100
0,0 5,0x106 1,0x107 1,5x107 2,0x107 2,5x107 3,0x107

1,2x107 1,2x107

6,0x106 6,0x106 3x10 0 3x100


L(1)
d
0,0 0,0

-6,0x106 -6,0x106

-1,2x107 -1,2x107
2x10 0 2x100
a(0,0)-a(1,1)
a(0,0)-a(1,1)

L(1,1)

(1)
-1,8x107 -1,8x107
L
a(0,0)
d
-a(1,1)
d
-2,4x107 -2,4x107
1x10 0 1x100
-3,0x107 -3,0x107 normal
-3,6x107 -3,6x107 diabetic
-4,2x107 -4,2x107 0 0

-4,8x107 -4,8x107
0,0 5,0x106 1,0x107 1,5x107 2,0x107 2,5x107 3,0x107 0,0 5,0x10 6 1,0x10 7 1,5x10 7 2,0x10 7 2,5x10 7 3,0x10 7
ω ω

Fig. 5. Difference between state coefficients for pb and db (Eqs. (22) Fig. 7. Displacement conductibility coefficient for pb and db
and (23)). (Eq. (24)).

1550021-9
F. Farsaci et al. J. Adv. Dielect. 5, 1550021 (2015)

106 107 10
4,0x1013 4,0x1013
G. A. Kluitenberg, On vectorial internal variables and dielectric
and magnetic relaxation phenomena, Physica A 109, 91 (1981).
3,5x1013 normal 3,5x1013 11
diabetic
V. Ciancio, F. Farsaci and G. Di Marco, A method for experi-
3,0x1013 3,0x1013 mental evaluation of phenomenological coefficients in media with
dielectric relaxation, Physica B 387, 130 (2007).
entropy production

2,5x1013 2,5x1013 12
V. Ciancio, F. Farsaci and P. Rogolino, Phenomenological ap-
2,0x1013 2,0x1013 proach on wave propagation in dielectric media with two relaxa-
tion times, Physica B 404, 320 (2009).
1,5x1013 1,5x1013 13
V. Ciancio, F. Farsaci and P. Rogolino, On a thermodynamical
1,0x1013 1,0x1013 model for dielectric relaxation phenomena, Physica B 405, 174
5,0x1012 5,0x1012
(2010).
14
F. Farsaci, V. Ciancio and P. Rogolino, Mechanical model for
0,0 0,0
relaxation phenomena in viscoanelastic media of order one, Phy-
106
107 sica B 405, 3208 (2010).
15
ω F. Farsaci and P. Rogolino, An alternative dielectric model for low
and high frequencies: A non-equilibrium thermodynamic ap-
Fig. 8. Trend of entropy production for pb and db (Eq. (45)). proach, J. Non-Equilib. Thermodyn. 37(1), 27 (2012).
16
H. P. Schwan, Electrical properties of blood and its constitutents:
function P ð0Þ has a minimum (for both db and pb) and P ð1Þ Alternating current spectroscopy, Blut 46(4), 185 (1983).
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