Molecular Medicines for Parasitic Diseases

*Bhawana Singh*

### **Abstract**

Being the cause for significant amount of morbidities and mortalities, parasitic diseases remain the major challenge for the healthcare community due to the limitations associated with the current chemotherapeutics. Drug discovery/invention can be achieved by collaborative efforts of biotechnologists and pharmacists for identifying potential candidates and successfully turn them into medicine for improving the healthcare system. Although molecular medicine for disease intervention is still in its infancy, however, significant research works and successful trials in short span of time have made it broadly accepted among the scientific community. This chapter identifies different molecular medicine approaches for dealing with parasites that have been coming up on the horizon with the new technological advances in bioinformatics and in the field of *omics*. With the better understanding of the genomics, molecular medicine field has not only raised hopes to deal with parasitic infections but also accelerated the development of personalized medicine. This will provide a targeted approach for identifying the druggable targets and their pathophysiological importance for disease intervention.

**Keywords:** CRISPR/Cas9 system, monoclonal antibody, immune checkpoint inhibitors, nanomedicine

#### **1. Introduction**

Parasitic diseases remain the threat to global healthcare sector, with considerable mortalities and morbidities associated with these diseases. Combating parasitic infection relies mostly on conventional chemotherapeutic approaches; however, an exponential rise in the number of recrudescent cases, lack of vaccines and toxicities issues associated with chemotherapies emphasized the need for the research to develop alternative strategies. It is noteworthy that emergence of drug resistance is not new; microbes have been evolving since ages, by knocking out one or the genes. In context of emerging drug resistance, World Health Organization (WHO) has warned for the upcoming "post-antibiotic era", therefore, molecular medicine has surged. Molecular medicine is the application of gene and/or DNA based information for therapeutic purpose. It involves the study of molecular mechanisms, identification of erroneous genetic and/or molecular pathways and development of molecular intervention with the aim to improve disease management.

This chapter provides an insight into how the anomalies in molecular pathways can be targeted leading to discovery of potential candidates for development of clinical medicine and innovative therapies to improve disease management strategies.

### **2. Evolution of molecular medicine**

The field of molecular medicine evolved over a period of time since the discovery of DNA (in 1953) and recombinant DNA technology. Another major breakthrough in 1975, when it was discovered that DNA can be read base by base through the sequencing technique. Later, in 1985, it was known that DNA can be amplified with PCR, and this was major achievement in the field of molecular diagnostics. This journey gained pace with the advent of automated DNA sequencing in 1987 that served as the background for the human genome project (HGP) in 1990. The journey of HGP started the era of modern molecular medicine with the first successful gene therapy. In 1995, the success of unveiling the DNA sequence from the first model organism (*Hemophilus influenzae*) triggered the endeavor towards the completion of HGP. The completion of HGP (in 2000) and the free access to the human genome sequences provided the ground for the advent of omics era or post-genomic era (or functional genomics) [1].

This led to the use of increasing number of analytical platforms for DNA sequencing termed as the next generation sequencing platforms. Further, metagenomics approaches—omics and/or shot-gun approaches paved the way for the third-generation sequencing, that aimed to reduce the sequencing costs. These advances gained momentum with the computational approaches where synthetic biology has remarkably facilitated the DNA based analysis as well as the development of models for drug testing.

In order to deal with the limitation of the existing chemotherapeutic approaches there remains an urgent need for the conversion of biomedical knowledge into clinical application. Molecular medicine provides the opportunity to fill the gap between the basic research and the clinical application for the diagnosis, prevention and treatment of diseases. It involves the combinatorial application of pharmacology, biomedical and omics technologies for understanding and improving the molecular basis of the disease pathogenesis that will serve in designing disease intervention strategies. Development of molecular drug is a complex process that involves multidisciplinary effort including high throughput screening, chemical synthesis, modification, omics technologies, data mining, structure-based drug designing, phenotypic screening, target and lead identification and validation, etc. The development of molecular medicines involves following steps—first, the identification of target, potential tractability of target (i.e. identifying targets that are more druggable than others, depending upon their chemistry), establish genetic association of target with disease pathophysiology (some targets required for drug action may not necessarily associate with disease genetics) and validation of target (by establishing association of target with the disease development/persistence). Validation of target usually involves different molecular approaches to understand the role of target gene or protein in diseases pathophysiology. Overall, it is an interdisciplinary branch where recent technical advances have served as the milestone in gaining insight into the phenomenon of disease pathogenesis and development of innovative therapeutic measures.

Parasitic diseases are amongst the common infections in humans caused by protozoan and helminthic parasites. The causative agents, parasites, are diverse ranging from single celled protozoan to worms that be seen with naked eyes. Till the end of nineteenth century, parasitologists were mainly focused on understanding their life cycle; however, the concept took turn when some parasites were found to be associated with several human diseases that led to significant morbidity and mortality. Parasitic diseases are cosmopolitan, that may affect any part of world however, mostly the diseases are common in tropical countries, but tourism and migration can transmit them outside their geographical boundaries. The signs and symptoms of disease may not be obvious, and it may vary from mild abdominal pain to chronic

**31**

**Diseases** **Protozoan parasites**

Leishmaniasis (visceral, cutaneous and mucocutaneous)

Malaria Chagas disease (American trypanosomiasis)

Human African Trypanosomiasis

*Trypanosoma brucei*

Tsetse fly (*Glossina*

species)

First stage-intermittent fever, headache, swelling of lymph nodes, joint pain; second

Pentamidine, suramin, fexinidazole, nifurtimox,

eflornithine

stage involves neurological symptoms

Headache, fever, fatigue, muscle ache; skin

Pyrimethamine, sulfadiazine, clindamycin,

spiramycin

Metronidazole

manifestation includes erythema and roseola

Pain, itchiness/burning in genitourinary

organs, urethritis, prostatitis (in males)

while frothy, foul-smelling discharge,

vaginitis (in females)

Chronic diarrhea, abdominal cramps,

Nitroimdazole, quinacrine, furazolidone,

paromomycin

Electrolyte replacement by rehydration therapy,

nitazoxanide, azithromycin, paromomycin

nausea and vomiting

Diarrhea, abdominal cramps, low-grade

fever (in intestinal cryptosporidiosis);

inflammation of nasal mucosa, cough,

shortness of breath, hypoxemia(respiratory

cryptosporidiosis)

Diarrhea, severe abdominal pain

Amebicidals (metronidazole, tinidazole) and

cysticidal agents (iodoquinol)

Toxoplasmosis Trichomoniasis

Giardiasis (beaver fever)

Cryptosporidiosis

Amoebiasis

*Entamoeba histolytica*

Feco-oral route

*Cryptosporidium*

species

*Giardia* species

Feco-oral transmission by

ingestion of cysts

Oral transmission

by consumption of

contaminated water,

undercooked food

*Trichomonas vaginalis*

Genital contacts

*Toxoplasma gondii*

Oral route; transmitted by

ingestion of parasite oocyst

*Trypanosoma cruzi*

Kissing bugs (Triatominae)

Fever, malaise, enlargement (liver, spleen, lymph nodes), sometimes skin nodules (chagoma); chronic stages affects the brain, heart and digestive system

*Plasmodium* species

Female mosquito *(Anopheles* species)

Headache, fever, paroxysm, joint pain, anemia, jaundice; neurological symptoms in severe cases

*Leishmania* species

Sandfly (*Phlebotomus* & *Lutzomyia* species)

Fever, anemia, splenomegaly, lymphadenopathy; cutaneous forms manifests as skin lesions and ulcers

Liposomal amphotericin B, miltefosine, antimonials; fluconazole, itraconazole

**Causative agent (pathogen)**

**Transmitting agent (vector)**

**Manifestation**

**Treatment options**

*Molecular Medicines for Parasitic Diseases DOI: http://dx.doi.org/10.5772/intechopen.91956*

Chloroquine, mefloquine, doxycycline

Benznidazole, nifurtimox

#### *Molecular Medicines for Parasitic Diseases DOI: http://dx.doi.org/10.5772/intechopen.91956*

*Methods in Molecular Medicine*

**2. Evolution of molecular medicine**

ment of models for drug testing.

The field of molecular medicine evolved over a period of time since the discovery of DNA (in 1953) and recombinant DNA technology. Another major breakthrough in 1975, when it was discovered that DNA can be read base by base through the sequencing technique. Later, in 1985, it was known that DNA can be amplified with PCR, and this was major achievement in the field of molecular diagnostics. This journey gained pace with the advent of automated DNA sequencing in 1987 that served as the background for the human genome project (HGP) in 1990. The journey of HGP started the era of modern molecular medicine with the first successful gene therapy. In 1995, the success of unveiling the DNA sequence from the first model organism (*Hemophilus influenzae*) triggered the endeavor towards the completion of HGP. The completion of HGP (in 2000) and the free access to the human genome sequences provided the ground for the advent of

This led to the use of increasing number of analytical platforms for DNA sequencing termed as the next generation sequencing platforms. Further, metagenomics approaches—omics and/or shot-gun approaches paved the way for the third-generation sequencing, that aimed to reduce the sequencing costs. These advances gained momentum with the computational approaches where synthetic biology has remarkably facilitated the DNA based analysis as well as the develop-

In order to deal with the limitation of the existing chemotherapeutic approaches there remains an urgent need for the conversion of biomedical knowledge into clinical application. Molecular medicine provides the opportunity to fill the gap between the basic research and the clinical application for the diagnosis, prevention and treatment of diseases. It involves the combinatorial application of pharmacology, biomedical and omics technologies for understanding and improving the molecular basis of the disease pathogenesis that will serve in designing disease intervention strategies. Development of molecular drug is a complex process that involves multidisciplinary effort including high throughput screening, chemical synthesis, modification, omics technologies, data mining, structure-based drug designing, phenotypic screening, target and lead identification and validation, etc. The development of molecular medicines involves following steps—first, the identification of target, potential tractability of target (i.e. identifying targets that are more druggable than others, depending upon their chemistry), establish genetic association of target with disease pathophysiology (some targets required for drug action may not necessarily associate with disease genetics) and validation of target (by establishing association of target with the disease development/persistence). Validation of target usually involves different molecular approaches to understand the role of target gene or protein in diseases pathophysiology. Overall, it is an interdisciplinary branch where recent technical advances have served as the milestone in gaining insight into the phenomenon of disease pathogenesis and development of innovative therapeutic measures.

Parasitic diseases are amongst the common infections in humans caused by protozoan and helminthic parasites. The causative agents, parasites, are diverse ranging from single celled protozoan to worms that be seen with naked eyes. Till the end of nineteenth century, parasitologists were mainly focused on understanding their life cycle; however, the concept took turn when some parasites were found to be associated with several human diseases that led to significant morbidity and mortality. Parasitic diseases are cosmopolitan, that may affect any part of world however, mostly the diseases are common in tropical countries, but tourism and migration can transmit them outside their geographical boundaries. The signs and symptoms of disease may not be obvious, and it may vary from mild abdominal pain to chronic

omics era or post-genomic era (or functional genomics) [1].

**30**

**Table 1.**

**33**

*Molecular Medicines for Parasitic Diseases DOI: http://dx.doi.org/10.5772/intechopen.91956*

lar medicines are underway.

**3.1 Targeting genome**

potential for future of molecular medicine.

zinc finger protein domain and nuclease domain. Cys

*3.1.1 Engineered meganucleases*

possible to cover some important parasites (**Table**

**3. Molecular medicinal strategies and parasitic diseases**

economic burden on families leading to viscous circle of poverty.

health through the understanding of mechanism in human diseases.

hepatomegaly and eventually death. Some parasitic infections are easily treated while others are not. In the light of the lack of vaccine for parasitic infection, proper prophylactic measures (proper hygiene, prevention of contaminated food, water, preventing consumption of undercooked food, use of bednets, insecticide spraying to prevent vector borne diseases, etc.) and active disease surveillance remains the key for disease elimination. Unfortunately, poor disease management strategies have made parasitic infections a global healthcare challenge. In this article it's only

Parasitic infections (protozoan and helminthic infections) affect more than a quarter world population and cause chronic illness primarily in developing coun

tries of world. These diseases affect the quality of life and treatment costs possess

Molecular medicine is a broad field that includes insight into the molecular aspect of diseases. Recombinant DNA and cloning technologies are the conven

tional tools for studying the disease associated molecular profiles. Recent technical advances have paved the way for utilization of several molecular strategies for treat

ing infectious diseases. Molecular medicine aims to understand the molecular basis of disease pathogenesis and allows the utilization of the information in designing specific diagnostic, therapeutic and prophylactic options. Mainly molecular medi

cine relies on two strategies—targeting genome and targeting signaling pathways, as targeted approach of disease management. Thus, it aims to improve the human

Apart from conventional approach of gene therapy (replacement of defective gene by exogenous DNA and editing mutated gene), recent technical advances have opened the arena for other strategies of manipulating the gene expression. Gene editing methods have gained limelight that involves the intrinsic molecular repair processes within the cell. The process of break repair in the DNA involves the homology-directed repair (HDR) and/or non-homologous end joining (NHEJ). The key step in gene-editing tool involves the precise introduction of double strand breaks. This process involves the use of engineered meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the recent CRISPR/Cas system [2]. Further, short antisense oligonucleotides potentially serve as tools for abrogating the transcription of target gene. As compared to other genome editing methods CRISPR/Cas system using guide RNA has shown immense

Although there remains plethora of meganucleases to choose from, however, most commonly used meganucleases include the ZFNs that have DNA binding

amongst the most abundant types of DNA binding motifs in eukaryotes [3, 4]. The ZFNs work by binding to the DNA and cleaving it, which then undergoes repair by either homologous recombination or error-prone NHEJ [5]. Site-specific cleavage is induced by manipulating the ZFN complex to recognize two sequences that are

2-His

2 zinc finger domain is

**1**), for which research on molecu

*Some parasitic diseases, their symptoms and treatment options.*

*Methods in Molecular Medicine*

#### *Molecular Medicines for Parasitic Diseases DOI: http://dx.doi.org/10.5772/intechopen.91956*

*Methods in Molecular Medicine*

**32**

**Diseases** **Helminthic diseases**

Roundworm infection (in

*Nippostrongylus*

Skin penetration

Emphysema, loss of alveolar septa, lung

Tetramisole

hemorrhage

Fever, cough, weight loss, abdominal

Albendazole, mebendazole

discomfort, intestinal ulcer accompanied

with eosinophilia

Acute phase marked by fever, nausea,

Bromofenofos, triclabendazole, bithionol

skin rashes, abdominal pain; chronic

phase manifests as jaundice, anemia and

intermittent pain

Mild (abdominal pain and nausea) to no

Praziquantel, albendazole, niclosamide, mepacrine

*braziliensis*

*Ascaris lumbricoides*

Feco-oral route

murine)

Ascariasis (Roundworm

infection, in human)

Fasciolosis

Taeniasis Onchocerciasis (subcutaneous filariasis)

*Onchocerca* species

Blackfly (*Simulium*

species)

Itchiness and bumps and depigmentation in skin to blindness

Ivermectin, moxidectin

Edema with skin thickening and underlying

Diethylcarbamazine citrate (DEC)

No specific treatment, supportive care helps reduce

the severity of symptoms

Praziquantel, oxamniquine, metrifonate, artesunate,

mefloquine

Filariasis (lymphatic and

*Wuchereria bancrofti*

Blackflies and mosquitoes

tissues

and *Brugia* species

*Angiostrongylus*

Oral route; upon ingestion

Headache, fever, malaise, nausea, neck

stiffness, varying degree of neurological

larvae in undercooked

prawn, snails, slugs, frogs

Contact with fresh water

contaminated with

parasites (released from

fresh water snails)

dysfunctions

Abdominal pain, diarrhea, fever, cough,

bloody stool and/or blood in the urine

*cantonensis*

serous cavity)

Neural angiostrongyliasis

(eosinophilic meningitis)

Schistosomiasis

Trichinosis

**Table 1.** *Some parasitic diseases, their symptoms and treatment options.*

*Trichinella spiralis*

Consumption of

Nausea, vomiting, fever, diarrhea, facial

Mebendazole, albendazole

undercooked pork

swelling

*Schistosoma mansonii*

*Taenia* species

Consumption of

undercooked pork or beef

symptoms

*Fasciola hepatica*

Oral route, consumption of

contaminated food

**Causative agent**

**Transmitting agent**

**Manifestation**

**Treatment options**

**(vector)**

**(pathogen)**

hepatomegaly and eventually death. Some parasitic infections are easily treated while others are not. In the light of the lack of vaccine for parasitic infection, proper prophylactic measures (proper hygiene, prevention of contaminated food, water, preventing consumption of undercooked food, use of bednets, insecticide spraying to prevent vector borne diseases, etc.) and active disease surveillance remains the key for disease elimination. Unfortunately, poor disease management strategies have made parasitic infections a global healthcare challenge. In this article it's only possible to cover some important parasites (**Table 1**), for which research on molecular medicines are underway.


**4. Test bench of dynamic pressure fluctuation for high-pressure common rail fuel injection system**

The test bench mainly includes the high pressure common rail injection system test stand, the operation stand and the water-cooling unit. It can measure the dynamic injection characteristics of a six-cylinder engine, such as the fuel injection rate, the fuel injection volume and the fuel injection duration for each cycle at most. The main functions of the high-pressure common rail fuel injection system test bench are to drive high pressure fuel pump, supply fuel to high pressure fuel pump at specified temperature and pressure, drive fuel injection system and real-time measure the dynamic injection characteristics of the system. The operation stand includes monitoring system, electronic control device for single injection instrument, driving equipment of fuel injector, programmable synchronous timing pulse generator, common rail pressure regulator, torque analyzer and DC power supply, etc. It can realize the real-time control and monitor of the experimental process. All of the experimental data results and the environmental parameters of each injector can be recorded after the experiment.

The high-pressure common rail fuel injection system test bench is shown in **Figure 3**. It consists of a driving motor, high pressure fuel pump, common rail, common rail pressure sensor, oscilloscope, single injection instrument, mechanical part of injection flow and rate (IFR), injector, pressure sensor, high pressure pipeline, electronic part of IFR, ECU, computer terminal and tank. The high pressure fuel pump is driven by the driving motor, which can provide a stable speed input for the system. The common rail pressure sensor installed on the common rail measures the common rail pressure in real-time and feeds the common rail pressure signal back to the ECU. The ECU adjusts the fuel flow into the common rail by adjusting the flow control valve on the high pressure fuel pump to stabilize the common rail pressure. In order to measure the dynamic pressure fluctuation at the injector inlet, a piezoresistive high pressure sensor is installed near the injector end on the high pressure pipeline between the common rail and the injector. The oscilloscope receives the pressure signal at the injector inlet measured by the pressure sensor and the common rail pressure signal measured by the common rail pressure sensor and stores

*Pressure Fluctuation Characteristics of High-Pressure Common Rail Fuel Injection System DOI: http://dx.doi.org/10.5772/intechopen.102624*

#### **Figure 3.**

*Schematic diagram of the high-pressure common rail fuel injection system test bench. 1. Drive motor 2. High pressure fuel pump 3. Common rail 4. Common rail pressure sensor 5. Oscilloscope 6. Mechanical part of IFR 7. Injector 8. Pressure sensor 9. High pressure pipeline 10. Electronic part of IFR 11. ECU 12. Computer terminal 13. Tank.*

the signal data. The ECU provides control current to the injector according to experiment conditions to complete fuel injection under different conditions.


5. Optimization of chitosan extraction by IR

4.3 Formula 3

niques such as NMR.

Table 4.

Figure 2.

114

FTIR spectrum of chitin and the baseline [73].

will be presented using IR.

In our study, a ratio had been already proposed [68, 71, 72]. However, choosing an appropriate calculation procedure was not an easy task since the choice of the baseline on FTIR spectra, reference, and the probe bands was difficult. In our work,

> A3450

where A1655 is the absorbance at 1655 cm�1 of the amide I band as a measure of

The baseline problem for reference peaks has been studied and summarized in Table 4 and Figure 2. Table 4 shows that there are other formulas for calculating chitosan DD by FTIR and that these formulas have been approved by other tech-

A synthesis of the study on the effect of the operating conditions to know temperature concentration of the base and the time on the reaction of deacetylation

DA calibration curve Method for DA standard Ref. 1. DA = (A1655/A3450) � 155 Titration [66] 2. (A1320/A1420) = 0.3822 + 0.03133 � DA 1H NMR, 13C NMR [67] 3. (A1320/A3450) = 0.03146 + 0.00226 � DA 1H NMR, 13C NMR [67] 4. (A1560/A2875) = 0.2 + 0.0125 � DA Elemental analysis [71]

∗ 100 1:33

(4)

DD% ¼ 100 � A1655

the N-acetyl group content and A3430 is the absorbance at 3430 cm�1 due to hydroxyl group as an internal standard. The value 1.33 represents the ratio of this absorbance for a fully acetylated compound. An appropriate baseline in each spec-

the average DD was determined by the following formula:

Calibration curves from absorption ratios versus standard DA values [73].

trum was determined by using origin software.

Modern Spectroscopic Techniques and Applications


3.1.3. Aldehydes

Among unsaturated aldehydes formed in the so-called LOX pathway, Buža, followed by Rosinjola and Oblica EVOOs, contained the highest concentrations of (*E*)- and (*Z*)-3-hexenal, respectively (Table 1). The same monovarietal EVOOs, with sporadic exceptions, were also distinguished by high levels of pentenals, hexadienals, and (*E*)-2-octenal. Oblica EVOO had high concentration of decadienals. Leccino was clearly distinguished from the other monovarietal EVOOs by the highest level of the major EVOO volatile, (*E*)-2-hexenal, as well as that of (*E*,*E*)-2,4-heptadienal. Leccino EVOO had the lowest concentration of (*Z*)-3-hexenal, although not statistically different from that found in I. bjelica and Lastovka EVOOs. Lastovka EVOO was characterized by rather low levels of particular LOX-derived hexenals, as well as pentenals, octanal, and hexadienals. Istarska bjelica contained low concentrations of (*Z*)-3-hexenal and decadienals. Among saturated aldehydes originating from the processes other than LOX, 3-methylbutanal turned out to be an exclusive marker of I. bjelica, while abundance in 2-methyl-2-pentenal was observed in Rosinjola EVOO (Table 1). Higher levels of hexanal clearly discriminated Dalmatian (Oblica and Lastovka) from Istrian monovarietal EVOOs.

**Table 1.** Concentrations (µg/kg unless otherwise stated) of volatile aroma compounds determined by gas chromatography-ion trap mass spectrometry (GC-IT-MS)after headspace solid-phase microextraction (HS-SPME) from monovarietal extra virgin olive oils produced from Buža, Istarska bjelica, Rosinjola, Oblica, Lastovka,and Leccino varieties in Croatia.

*Foods***2019**, *8*, 565

*Foods***2019**, *8*, 565

*Foods***2019**, *8*, 565

semi-quantitatively

letters in a row represent

 and their

 statistically

 significant

 differences

 between mean values at *p* < 0.05 obtained by one-way ANOVA and least significant

concentrations

 were expressed

 as equivalents

 of compounds

 with similar chemical structure

 assuming

 a response factor = 1. Different superscript

 difference

 (LSD) test.

 lowercase


*5.1. Summary of the Results*

In summary, our results showed that the most important factor affecting phase change was the participation in the study. The longer the participants remained in the study, the higher was the chance that they progressed from the pre-decisional to pre-actional stage and from the actional to the post-actional stage. Moreover, the time of measurement affected energy monitoring.

We found no differences between the control groups and the experimental group. One explanation could be purely statistical, the power of the performed test was too low. That is, the effects we tested were too small to detect with the sample size we had. Another explanation, which seems more plausible, is that participation in such a demanding study even in the control group in which participants completed a number of questionnaires was an experience strong enough to affect changes. Numerous studies in psychology show that an investment of effort in some issues makes people value the given cause more [55]. In other words, effort invested could have given additional value to energy monitoring even in the control group. This interpretation could be additionally supported by the results showing that participants were more eager to engage in energy monitoring as the study progressed.

Participation in the study also affected attitudes towards environmental issues, but to a lesser extent. Thus, the participation in the study was more effective for a variable closer related to behaviors referring to the control of energy consumption.

Knowledge about energy market was correlated with participants' energy monitoring. This is quite an intuitive result as probably specific knowledge provided know-how for participants in the study. More surprising are the results that education was negatively related to energy monitoring. We may speculate that participants with higher education have more absorbing professional lives and spend more time in front of the computer. Therefore, they are less willing to control energy, using technology in their spare time.

For most of the participants, monitoring energy by means of SMP has similar pros and cons. The higher control over one's energy consumption and better energy management belonged to the biggest advantages of using SMP, whereas time consumption and low effectiveness in terms of financial savings were mentioned as the biggest disadvantages and barriers of regular SMP usage. For such consumers, the energy supplier should offer automatic transmission of e.g., daily reports on energy consumption or information on exceeding a given level of energy consumption (e.g., daily limit set by the energy consumer according to his own needs). Such services could increase the level of interest and engagement in SMP usage.


**Meet the editor**

Dr Jesús Hamilton Ortiz has obtained his Bachelors' degrees in Mathematics and Electrical Engineering, DEA in Telecommunications Engineering and a PhD in Computer Engineering. Currently, he is an Assistant Professor at the University of Castilla La Mancha in Computer and Mobile Networks. Professor Ortiz is an editor and reviewer of several international journals and director

of closemobile.com. Additionally, he is an assessor of projects concerning applications in Telecommunications and Mobile Networks and a supervisor of bachelor and master degree thesis. He is interested in the following topics: New Generation Networks, 4G, Routing Protocols, QoS, Sensor Networks, VANET, UAVs, etc.

Contents

**Preface IX**

Chapter 1 **Access Control Solutions**

**Part 1 New Generation Networks 1**

and A.F. Gomez-Skarmeta

Chapter 2 **IP and 3G Bandwidth Management**

and Priscila S. Barreto

M. Errais and M. Ramdani

**Part 2 Quality of Services 75**

Wei Zhuang

**Part 3 Sensor Networks 127**

Chapter 7 **Review of Optimization Problems**

Chapter 4 **A Testbed About Priority-Based**

**for Next Generation Networks 3**  F. Pereniguez-Garcia, R. Marin-Lopez

**Strategies Applied to Capacity Planning 29**  Paulo H. P. de Carvalho, Márcio A. de Deus

Chapter 3 **eTOM-Conformant IMS Assurance Management 51**

**in QoS Wireless Multimedia Networks 77**  A. Toppan, P. Toppan, C. De Castro and O. Andrisano

Chapter 5 **End to End Quality of Service in UMTS Systems 99**

Chapter 6 **Power Considerations for Sensor Networks 129**  Khadija Stewart and James L. Stewart

**in Wireless Sensor Networks 153**

Ada Gogu, Dritan Nace, Arta Dilo and Nirvana Meratnia

M. Bellafkih, B. Raouyane, D. Ranc,

**Dynamic Connection Profiles**