\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"3780",leadTitle:null,fullTitle:"Petri Nets Applications",title:"Petri Nets",subtitle:"Applications",reviewType:"peer-reviewed",abstract:"Petri Nets are graphical and mathematical tool used in many different science domains. Their characteristic features are the intuitive graphical modeling language and advanced formal analysis method. The concurrence of performed actions is the natural phenomenon due to which Petri Nets are perceived as mathematical tool for modeling concurrent systems. The nets whose model was extended with the time model can be applied in modeling real-time systems.\r\n\r\nPetri Nets were introduced in the doctoral dissertation by K.A. Petri, titled “„Kommunikation mit Automaten” and published in 1962 by University of Bonn. During more than 40 years of development of this theory, many different classes were formed and the scope of applications was extended. Depending on particular needs, the net definition was changed and adjusted to the considered problem. The unusual “flexibility” of this theory makes it possible to introduce all these modifications. Owing to varied currently known net classes, it is relatively easy to find a proper class for the specific application. The present monograph shows the whole spectrum of Petri Nets applications, from classic applications (to which the theory is specially dedicated) like computer science and control systems, through fault diagnosis, manufacturing, power systems, traffic systems, transport and down to Web applications. At the same time, the publication describes the diversity of investigations performed with use of Petri Nets in science centers all over the world.",isbn:null,printIsbn:"978-953-307-047-6",pdfIsbn:"978-953-51-5867-7",doi:"10.5772/150",price:159,priceEur:175,priceUsd:205,slug:"petri-nets-applications",numberOfPages:764,isOpenForSubmission:!1,isInWos:1,hash:"b1f80da4d06e2b7b4076e74797319265",bookSignature:"Pawel Pawlewski",publishedDate:"February 1st 2010",coverURL:"https://cdn.intechopen.com/books/images_new/3780.jpg",numberOfDownloads:67446,numberOfWosCitations:19,numberOfCrossrefCitations:18,numberOfDimensionsCitations:51,hasAltmetrics:0,numberOfTotalCitations:88,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 30th 2013",dateEndSecondStepPublish:"August 20th 2013",dateEndThirdStepPublish:"November 24th 2013",dateEndFourthStepPublish:"February 22nd 2014",dateEndFifthStepPublish:"March 24th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"4487",title:"Dr.",name:"Pawel",middleName:null,surname:"Pawlewski",slug:"pawel-pawlewski",fullName:"Pawel Pawlewski",profilePictureURL:"https://mts.intechopen.com/storage/users/4487/images/3685_n.jpg",biography:"Paweł PAWLEWSKI, PhD, is Assistant Professor at the Faculty of Engineering Management at Poznan University of Technology. His area of interest comprises: modeling, process simulation and optimization, organization of manufacturing processes, operational management, reengineering and IT applications in logistics. He is the author or co-author of more than 100 scientific papers. He is also co-author of the book “Reengineering”. In 1994-2008 he managed a team performing a software for design and optimization of mechanical structures implemented among other things in VW-Wolsburg, VW-Shanghai, Audi-Ingolstadt, Seat-Barcelona, Porsche-Stuttgart, BMW–Munchen. All actions were taken within vMACH Engineering company. In 2009-2011 he cooperated with AMC Polska company in the scope of process simulation and optimization with the usage of Witness. Since 2011 he is a Manager of Simulation and Optimization Center in Logistic and Production Processes (SOCILAPP) at Poznan University of Technology. Habilitation dissertation titled “ Methodology of modeling dynamic changes of production process’ resource structure in mechanical engineering industry” is under accreditation procedure. Since 2011 he cooperates with Cempel Consulting. He is also a Flexsim Software Products Inc. (USA) Partner in Poland. Since 2012 he is member of Editorial Board (as Associate Editor) of International Journal of Artificial Intelligence (IJAI).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Poznań University of Technology",institutionURL:null,country:{name:"Poland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"616",title:"Mathematical Modeling",slug:"theory-of-computation-mathematical-modeling"}],chapters:[{id:"9175",title:"An Application of GSPN for Modeling and Evaluating Local Area Computer Networks",doi:"10.5772/7524",slug:"an-application-of-gspn-for-modeling-and-evaluating-local-area-computer-networks",totalDownloads:1637,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Masahiro Tsunoyama and Hiroei 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El-Hazmi",authors:[{id:"60259",title:"Prof.",name:"Mohsen",middleName:"Ali Faris",surname:"El-Hazmi",fullName:"Mohsen El-Hazmi",slug:"mohsen-el-hazmi"},{id:"104018",title:"Dr.",name:"Ali",middleName:null,surname:"El-Hazmi",fullName:"Ali El-Hazmi",slug:"ali-el-hazmi"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"63203",title:"Virulence Factors of Uropathogenic E. coli",doi:"10.5772/intechopen.79557",slug:"virulence-factors-of-uropathogenic-e-coli",body:'
The most commonly living microorganism of the human gastrointestinal tract and also the most common causative agent of bacterial urinary tract infection is E. coli [1]. Though they remain in a good relationship with their hosts, they might appear as a subject of consideration in immunocompromised hosts. This common inhabitant of the gastrointestinal tract usually remains in a symbiotic relationship with the host and plays a role in maintaining the homeostasis of the intestinal tract. Though most of the strains of E. coli are harmless, some serotypes can cause food poisoning. E. coli present in the normal human microbiota produces vitamin K2. Strains of E coli, however, obtaining ability to colonize inside the urinary tract and to make themselves safe from the host immune system, become uropathogenic E. coli. UPEC causes >80% of UTI [2]. Urinary tract infections are very common, and approximately 10% of people [3] and half of all women (at least one time) become infected throughout their life. According to a study, more than 100,000 patients in the United States are hospitalized annually due to urinary tract infections [4], and in the year 2011, 400,000 patients were hospitalized, and the estimated cost was about 2.8 billion USD [5]. Infections can occur in both upper and lower urinary tracts. Lower urinary tract infection is known as cystitis, and in the case of upper urinary tract infection, it is called pyelonephritis. Without distinction of site, in order to cause infection, the causative agent must at first dodge the host’s immune system and colonize in the urinary tract [6]. Several different virulent factors are needed for the bacterial population to cause infections [7]; for instance, pathogenic strains of E. coli express adherence factors which form pili or fimbriae of different types for their attachment in the sites where they usually do not live [7]; these are structural virulence factors and predominantly include P fimbriae and type 1 fimbriae [1]. Fimbrial adhesins such as PapG and CsgA are virulence factors that facilitate the attachment of E. coli [8]. In animal models, type 1 fimbriae aggrandize the chance survival of E. coli [9]. Beside these, UPEC can impair host immune system by a variety of ways [10], such as toxins and iron acquisition systems, and these are called secreted virulence factors. The production of these virulence factors by UPEC may cause an inflammatory response which makes a possible pathway for UTI symptoms [1]. However, both the host and the uropathogenic E. coli strain have different roles in the establishment and colonization process in the urinary tract [11]. Here in this chapter, different types of important virulence factors of uropathogenic E. coli will be discussed.
In Gram-negative and some Gram-positive bacteria, virulence genes are allocated in particular segments (about 10–200 kilo bases in size) of their genome which have different G + C content than the other parts of the genome that are termed as pathogenicity islands. They are present in the virulent strains but present rarely in the nonpathogenic strains of the same species. These sequences can be transferred horizontally from species to species [12]. Pathogenicity islands encode virulence factors such as adherence factors, toxins, and iron acquisition systems which are important virulence factors of UPEC.
Urine of uninfected person is sterile due to urinary flow and antimicrobial activity of uric acid. Regular flow of urine does not allow microorganism to colonize inside the urinary tract. However, attachment of E. coli to uroepithelial cells allows them to overwhelm the effect of urine flow. For many pathogenic microorganisms, it is considered as the first step in the colonization process [13, 14], and both the host and E. coli function in this process. The ability of UPEC to colonize depends upon the expression of different fimbrial adhesins. For a successful adherence to the host cell surface, UPEC expresses many adherence factors which are crucial for attachment and thus regarded as virulence factors. Many bacterial adhesins are organized in a thin filamentous structure called fimbriae or pili although there are evidences of presence of adhesins in the cell surface of bacteria. Adhesins of fimbrial nature are important during attachment process [15]. Fimbriae, also known as pili, are long hair-like structures contained in the cell surface of bacteria that recognize specific compounds usually carbohydrates of the target host cells [11]. Pili are the short form of fimbriae and might be used interchangeably with fimbriae. Fimbriae consist of oligomeric pilin proteins. These proteins are arranged in such a manner that they form a helical cylindrical structure and are both thinner and shorter than flagellum. These proteinaceous structures are expressed in uropathogenic strains of E. coli and are considered as virulence factors [11]. Most of the receptors for these fimbriae are carbohydrates. They include type 1 fimbriae, P fimbriae, and thin aggregative fimbriae [16]. Many bacterial pathogens can produce an array of these adhesins, and often inhibition of a single adhesin may cost enough to a bacterium to lose its virulence. Functions of pili or fimbriae are not limited only to adhesion and can help in many other crucial pathways for the microbe to survive and evade the immune system of the host. Evolution of different types of adhesins plays a role in tissue tropism.
In gram-negative bacteria like UPEC, adhesins are unveiled by chaperone-usher-assisted pathway. This pathway involves two proteins, one is a periplasmic chaperone, and the other is a protein called usher. Usher act as the base of the structure, and the function of chaperone is folding and recruitment of the subunits [17, 18]. In absence of the chaperone, pilin proteins are degraded and misfolded and thus cannot be assembled in the form of a mature pilus. On the other hand, usher helps to mature the fimbriae and its transportation through the outer assuring integrity of the outer membrane. The constituents of usher proteins are an N-terminal domain (NTD), 24-stranded beta-barrel channel, a plug domain, and two C-terminal domains (CTD). In uropathogenic E. coli strains, chaperone-usher family fimbriae are more abundant.
In 99% of E. coli strains, genes to encode type 1 fimbriae are present [19], and during urinary tract infections, they damage urinary tract cells by mediating an increased inflammation [20]. In order to enter into the host cells of the urinary tract, type 1 fimbriae play a great role. Type 1 fimbriae are remarkably versatile virulence factors of UPEC that can stabilize the attachment of the bacteria to different type of cells throughout the urinary tract. Though in Bowman’s capsules and glomerulus their binding sites could not be identified, a strong affinity of type 1 fimbriae was found in proximal tubules and vessel walls. In the bladder, they bind strongly to muscular layers and moderately to vessel walls. Receptors for type 1 fimbriae were also found in the distal tubules and collecting ducts. They can also induce their binding to the surface of macrophages [9]. These fimbriae recognize uroplakin from bladder epithelial cells and mannoside-containing host proteins. Unlike many other important types of adhesins, these are encoded by the bacterial backbone DNA [21] and are mainly composed of FimA proteins along with FimF, FimG, and FimH [17]. FimA proteins are most in number but are not pivotal for virulence. Among other subunits of type 1 fimbriae, allelic variations of FimH determine the sugar specificity and deletion of fimHresults in less amount of colonization in mouse models of ascending UTI, and colonization could be restored by expression of plasmid with fimH gene [20]. FimH alone or in association with LPS can stimulate toll-like receptor 4 (TLR4) to initiate particular signaling cascade that may activate the humoral immune response. Many studies revealed that expression of type 1 fimbriae results in virulence and loss of expression results in loss of expression but their presence cannot be correlated with UTI as normal fecal strains also have equally expressed type 1 fimbriae [22]. However, type 1 fimbriae-mediated attachment is a crucial stage for cystitis. Adhesins of these fimbriae are mannose sensitive.
P-fimbriated E. coli are pyelonephritogenic and attach to the carbohydrate structure alpha-D-Galp-(1-4)-beta-D-Galp. In the kidney, they bind strongly to Bowman’s capsule, glomerulus, and endothelial cells of vessel walls. This highly organized composite structure is composed of six subunits at least. Once P fimbriae expressed E. coli enter the urinary tract, they establish bacteriuria and help to cross the epithelial barrier to enter the bloodstream and can cause hemagglutination of erythrocytes [14]. This type of fimbriae is encoded by pap gene cluster (also known as fso and fst), and pap + strains remain longer in the intestinal flora than pap- strains [23]. P antigens are expressed in the cell surface of red blood cells and in various cells lining in the urinary tract. P1 (present in glycoproteins in human), P, PK, and LKE antigens act as the receptors for P-fimbriated UPEC. P-fimbriated E. coli cannot agglutinate red blood cells that lack P antigen. Isolated P fimbriae can bind to a synthetic analogue of its receptor, and experimental application of that analogue impedes infection process.
There are at least nine genes in the pap gene cluster with two restriction sites at two ends. The regulatory part starts the following Eco R1 consisting of papI and papB. Then papA, papH, papC, papD, papE, papF, and papG are situated, and after these, Bam HI is present. Approximately 1000 of subunits form a P fimbria, being united in a helical manner. Among them the major constituent is the protein subunit PapA (19.5 KD), and minor subunits are PapE (16.5 KD), PapF (15 KD), and PapG (35 KD). In the periplasmic space, PapD (27.5 KD) may be present and can also be incorporated in the structure. Another protein PapC, which is the largest one with 80 KD of mass, assists the process by transporting the subunits outside the part of the cell. Though PapA is the major constituent, it is not mandatory for attachment, and among many serotypes, PapA molecules show high homology with the amino acids of N and C termini. PapA also has an average level of similarity with structural subunits of other E. coli fimbriae including type 1 fimbriae. The minor subunits at the tip of fimbria determine the specificity to the receptor. Many mutational analyses revealed that mutation in PapA does not affect the adherence, while mutation in other genes (i.e. papEFG) does not hamper fimbrial structural appearance. In the fine structure of P fimbriae, a PapF-PapG complex is formed which is attached to PapA (bulk potion of the structure) subunits through PapE subunits. Finally, PapH terminates the assembly of the fimbriae and attaches thereby [16]. An important thing is that the amino acid sequence of PapG is approximately similar to that of Shiga toxin. Shiga toxin is found in some serotypes of E. coli. Another role of PapG was found in some variants of P fimbriae which is they can initiate subunit polymerization [14].
Many experiments show that expression of these fimbriae is not relevant to urinary tract infection, while more sophisticated other experiments have concluded about their role in pathogenesis. However, during infection in immunocompromised patients, less expression of P fimbriae is observed, which indicated that P fimbriae are needed to overcome certain types of host immune attacks. Although P fimbriae can initiate inflammatory responses by activating TLR4 [24], it protects UPEC from human polymorphonuclear leukocytes (hPMNLs). In the rapidly changing environment through the urinary tract, environmental influences affect the expression of P fimbriae. Expression of P fimbriae is favored at 37°C and inhibited at a range of 18–22 °C, but there are some variations in this phenomenon. The temperature-dependent expression is controlled by a region close to papB of the pap gene cluster.
Dr blood group antigen is a membrane protein of red blood cells and located on the decay accelerating factor (DAF) that protects red blood cells from being degraded or lysed by autologous complements. Another important function of DAF is to regulate complement cascade [25]. These antigens are recognized by Dr and Afa adhesin family of uropathogenic E. coli. There are both fimbrial (F1845 and O75X) and non-fimbrial (AFA I and AFA II) types of adhesins. Immuno-invasion of UPEC by hiding from the host humoral immune response is somehow mediated by Dr family of adhesins [26]. These microscopically invisible fimbriae are present in the cell wall, and their structural and organization properties are quite different from other types of fimbriae [13]. Chloramphenicol can inhibit O75X binding to a specific part of the Dr antigen, but it cannot inhibit other adhesins of this family which indicates that Dr family adhesins can recognize specific sites at the Dr [25]. For years, several studies were conducted to identify specific sites for binging of Dr family hemagglutinins. For instance, a strong affinity of O75X was found to Bowman’s capsule, proximal and distal tubules, and the collecting duct basement membranes. In the bladder, they strongly bind to connective tissues.
F1C is a virulence factor responsible for urinary tract infections, which is encoded by an operon of seven genes, i.e., focAICDFGH, where FocA is the major subunit and FocH is the tip adhesin [26]. F1C receptors are present in bladder endothelium and muscular layer. They cannot bind to the epithelium. They bind to glomeruli, distal tubules, collecting ducts, and vascular endothelial cells. Studies show that F1C fimbriae and pyelonephritis are correlated though there is a little difference in the prevalence of type 1 fimbriae in UTI strains and normal fecal isolates. Prevalence of F1C fimbriae in normal fecal isolates is 10% which is 16% in UTI strains [26]. S fimbriae are genetically identical to F1C fimbriae and differ only by the tip adhesin SfaS. Criteria that are needed to be recognized as a virulence factor were determined by different studies regarding S fimbriae. There are some other adhesins that are not crucial for the survival of UPEC strains such as F9 fimbriae.
Several toxic substances or proteins secreted by uropathogenic strains of E. coli play a consequential role as virulence factors in UTIs. However, toxins have the ability to alter the host cell signaling cascade and modulate inflammatory responses. Several in vitro and in vivo studies showed that toxins also contribute to the stimulation of the host cell death and releasing of necessary nutrients, which provide the ability to access deeper tissues within the urinary tract [27]. In 1987, CDT toxin (cyclomodulins) was first reported as virulent toxin in UPEC [28] which opened a new door in the study of the pathogenesis of UTIs, and then many other toxins in UPEC were reported including α-hemolysin (HlyA), cytotoxic necrotizing factor 1 (CNF1), secreted autotransporter toxin (SAT), cytolysin A, plasmid-encoded toxin (PET), vacuolating autotransporter toxin (VAT), Shigella enterotoxin-1 (ShET-1), arginine succinyl-transferase (AST), etc.
Among all the toxins, α-hemolysin (HlyA) is very important which is a lipoprotein and belongs to the RTX (repeats in toxin) toxins family [13, 29, 30]. HlyA is a pore-forming toxin and causes inducible nitric-oxide-synthase (iNOS)-mediated cell membrane injury and apoptosis [31]. However, HlyA can lyse erythrocytes and nucleated host cells at high concentration by a process enabling UPEC which may damage the host immune effector cells for gaining enhanced access to the host nutrients and iron stores. But when the concentration is low, HlyA can induce the apoptosis of target host cells and promote the exfoliation of bladder epithelial cells [13, 32, 33]. Besides, HlyA can also contribute to nephropathogenicity, which was proved by infecting mice transurethrally or intravesically with toxin producer and nonproducer isogenic clone pairs of E. coli [34]. A recent study showed that HlyA regulates the dephosphorylation of Akt, which is a multifunctional signaling regulator and responsible for controlling inflammatory responses in the host, as well as the cell cycle control [35]. Moreover, HlyA has the role in the increased production of IL-6 and IL-8 by inducing Ca2+ oscillations in renal epithelial cells [36].
Another virulence factor secreted by E. coli named cytotoxic necrotizing factor 1 (CNF1) is also involved in UTIs and stimulates actin stress fiber formation and membrane ruffle formation in a Rho GTPase-dependent manner that results in the entry of E. coli into the cells [37]. The toxin has a remarkable effect on the actin skeletal of HEp-2 cells and produces large vacuoles in HEp-2 cells [28]. However, several in vitro and in vivo studies showed that this protein interferes with polymorphonuclear phagocytosis and evokes apoptotic death of bladder epithelial cells and may lead to bladder cell exfoliation and to enhanced bacterial access to underlying tissue [38, 39]. In addition, there is also a possibility of the association of CNF1 with the hemolysin in the virulence mechanism, which is beneficial for the bacteria [28].
Secreted autotransporter toxin (SAT) may also be important as a virulence factor for the pathogenesis of UTIs being had a toxin activity against cell lines of bladder or kidney origin. SAT is a serine protease autotransporter which falls within one subgroup of autotransporters recently classified as the SPATE (serine protease autotransporters of Enterobacteriaceae) family and associated with pyelonephritic E. coli strains [40, 41]. SAT may have the cytopathic activity that results in the damage of the host tissue and may increase the propagation ability of the UPEC. However, this toxin may facilitate entry of pyelonephritogenic strains into the bloodstream resulting from specific damage to the glomeruli and proximal tubules [40].
Cytolethal distending toxin, having a unique property of damaging the DNA of the target cell, was first reported in pathogenic E. coli in 1987 [28, 42]. This toxin has the ability to arrest the cell cycle and contributes to the pathogenesis of UTIs [43, 44]. However, CDT is an operon product encoding three proteins including CdtA, CdtB, and CdtC proteins which are encoded by cdtA, cdtB, and cdtC genes, respectively [28]. CDT has DNase I-like enzymatic activity and attacks DNA, while the other bacterial toxins attack the cell membrane or different targets within the cytoplasm [45]. This unique property of attacking DNA damages the target cell DNA which results in progressive cell distending leading to cell death [27].
Some others including cytolysin A and toll/interleukin (IL-1) receptor (TIR) domain-containing protein (Tcp) are also considered as virulence factors in UTIs [46, 47]. The former causes apoptosis of the host cells [47], while the other has the ability to subvert TLR signaling that gives a survival advantage during UTIs [46]. However, Tcp is associated with pyelonephritis but rare in environmental E. coli, in fecal flora of healthy children and in less severe forms of UTI [27]. Besides these, Tcp has also the role in the human avoidance system and cytopathic effect on the kidney [48].
In addition to these toxins, vacuolating autotransporter toxin (VAT), Shigella enterotoxin-1 (ShET-1) and arginine succinyltransferase (AST) may also contribute to UTIs. VAT has the cytotoxic effect on the bladder and kidney, while the two others are involved in the invasion of the infections [48]. However, VAT is a highly protected immunogenic protein that belongs to the protease family of SPATE [28].
Iron is a very important molecule for all living beings, and E. coli uses iron for transporting and storing oxygen, DNA synthesis, electron transport, and metabolism of peroxides. But the amount of iron availability is reduced in the host urinary tract during UTIs [49]. In response to this, E. coli possesses some multiple functionally redundant systems that mediate iron uptake by secreting low-molecular-weight Fe3+-chelating molecules which are known as siderophores [50]. Iron utilization, mediated by these siderophores, is critical for colonization of the urinary tract by UPEC [51]. There are four distinct siderophore systems found in E. coli such as yersiniabactin, aerobactin, enterobactin, and salmochelin [52]. These systems also include some genes such as ent genes encoding enterobactin, iuc genes encoding aerobactin, and iro genes encoding an ent-like system. However, all these systems are expressed under low-iron conditions and are negatively regulated by ferrous iron and the ferric uptake regulator Fur [53].
Aerobactin is a low-weight molecule and a hydroxamate siderophore with a higher Fe3+-binding stability in acidic environments and is maximally produced at low pH [44, 53]. This siderophore extracts Fe3+ from host iron-binding proteins and is taken up through an outer membrane receptor protein [44]. However, aerobactin has many advantages over other siderophores and is formed from the condensation of two lysine molecules and one citrate catalyzed by an enzyme named aerobactin synthase [13, 25, 30].
Enterobactin is another specialized highly prevalent catecholate siderophore which is less soluble and less stable than aerobactin [53, 54, 55]. But this siderophore has a higher iron affinity and can deferrate transferrin more rapidly than aerobactin in aqueous solution [13, 54]. However, iron is released from enterobactin through the hydrolysis of this siderophore [13]. Besides these, enterobactin may afford UPEC the ability to colonize within an iron-limiting environment such as the urinary tract [56]. But this siderophore has a limitation that it can be inactivated by host proteins such as serum albumin and siderocalin [25].
Yersiniabactin, a mixed-type siderophore, is widespread in Enterobacteriaceae including E. coli and encoded on the high-pathogenicity island [53]. Yersiniabactin has a high iron affinity and produced yersiniabactin-Fe3+ complex binding to the iron molecule which recognizes the specific bacterial outer membrane TonB-dependent receptor and Fyu (Psn). The iron molecule is released from yersiniabactin in the cytosol with the help of membrane-embedded proteins [57]. In addition, this siderophore increases resistance to copper stress by chelating Cu2+ [10].
Salmochelin is a glucosylated derivative of enterobactin which is not recognized by siderocalin and thus escapes from the host immune response [53]. However, siderocalin, neutrophil gelatinase-associated lipocalin is also known as lipocalin 2 that binds enterobactin and prevents its uptake [53, 56]. To overcome this, enterobactin is modified to salmochelin by glucosylation via the action of glucosyltransferase and is not recognized by lipocalin 2 [56]. However, a recent study found that salmochelin siderophore receptor IroN is involved in the invasion of urothelial cells, and thus IroN may play both an iron uptake receptor and an internalization factor in the establishment of urinary tract infections [26].
There is another iron acquisition system called hemin uptake system including ChuA and Hma, which involves direct upregulation of haem receptors. This system uptakes free iron during UTIs, and several studies found its role in bacterial growth and biofilm formation [48, 58, 59]. ChuA expression is regulated by other regulatory proteins, for instance, in uropathogenic E. coli strain 536, increase in RfaH level induces the expression of ChuA [60]. But the other receptor Hma functions independently of ChuA, and a residue, Tyr-126, is necessary for its function. However, both ChuA and Hma contribute to haem utilization which is required for the maximum kidney colonization [51].
The main role of a capsule is to cover and protect the bacterium from various unfavorable conditions as well as the host immune system, which is mainly constituted of polysaccharide [1]. The capsule provides protection against engulfment and complement-mediated bactericidal effect in the host, also including antimicrobial resistance and antiserum activity [1, 48]. Certain capsulars, such as K1 and K5, prevent a proper humoral immune response of the infected host by showing a molecular mimicry to tissue components [1]. The K1 polysaccharide, a linear α2–8-linked sialic acid homopolymer, has a very important role in IBC development as well as in the multiple stages of UTI pathogenesis [27, 50].
Lipopolysaccharide (LPS) is an integral component of the cell wall and consists of the highly conserved lipid A-core and repeating O-antigen subunits that differ greatly between strains based on the sugar residues and their linkage patterns within the repeating subunits [37, 61]. LPS is very well known to activate host response and to induce nitric oxide and cytokine (IL-1, TNF-α) production which enhances the inflammatory response [1, 15]. It also induces the synthesis of specific antibodies to the somatic antigen and exerts an immune-adjuvant effect that promotes the humoral immune response to other antigens of the pathogen. However, certain antigenic types of LPS are also involved in resistance of the pathogen to the killing effect of the normal human serum [46]. According to study upon animal models, acute renal failure due to LPS depends on the systemic response to LPS and does not depend on expression of functional LPS receptor, TLR4, in the kidney. But it is not clear whether LPS plays a role in mediating a renal failure and acute allograft injury in patients with ascending UTIs [1].
Flagellum is an organelle that is responsible for bacterial motility and plays a role in the initial adhesion phase of biofilm formation [1, 62]. A recent study showed that motility is involved in the migration of the infection from the bladder to the kidneys [63]. About 70–90% of all urinary tract infections is caused by flagellated UPEC, and pathogenesis involves contact between the bacteria and epithelial cell surface of the urinary tract [1]. However, flagellar motility enhances the ability of E. coli by adaptive responses to attractive or repellent environmental stimuli [15].
Toll-like receptor 4 (TLR4) in the epithelial cells of the mammalian bladder can recognize lipopolysaccharides (LPS) of bacterial cell wall, and the downstream signaling cascade produces IL-6 and IL-8, of which IL-8 is well known as an important chemoattractant for neutrophils. Urinary levels of IL-6 and IL-8 are measurable in UPEC-infected human and murine models. There is another pathway parallel to this one that is responsible for increased levels of IL-6 and IL-8 in urine. Upon TLR-4 activation by LPS, intracellular level of cAMP is increased and results in of Ca2+ influx. Later, cAMP response element-binding protein (CREB) becomes phosphorylated. Phosphorylation of CREB results in the expression of IL-6 and IL-8 [24]. Mutation in TLR4 in murine models revealed its role on bacterial pathogenesis. There are other receptors related to UTI pathogenesis. One of such is CXCR1, but there are both types of evidences that demonstrate the positive and “no correlation” of CXCR1 with recurrent UTIs. Polymorphisms in IL-8 genes were found to have a correlation with pyelonephritis in the case of no correlation with CXCR1 mutation [19, 64]. TLR4 can be activated by the presence of type 1 fimbriae and P fimbriae.
As there are enough studies to evidence the activation of immune response against UPEC strains, there must be some ways that are used by these bacteria to overcome unfavorable situations early in the infection. Incubation of human urothelial cells with type 1-fimbriated UPEC strains resulted in increased apoptosis. In the case of a nonpathogenic type 1-fimbriated strain (HB101) of E. coli, rate of apoptosis was approximately 50% of that of pathogenic strains of UPEC [65]. UPEC blocks NF-ĸB, and this results in apoptosis and a decreased cytokine secretion.
Another indispensable way is the expression of toll/IL-1 receptor domain-containing protein (TcpC), which was discovered in UPEC strain CFT073. TcpC interacts with myeloid differentiation primary response 88 (MyD88), a protein that, in human, is encoded by MYD88 gene. Interaction of TcpC and MyD88 subsequently stops downstream signaling pathways mediated by TLRs.
Modification of capsular lipopolysaccharides specific to the pathogenic strain can cause the failure of TLR4 to recognize the pathogen. However, LPS biosynthetic genes encoded by rfa, rfb operons, and surA are the factors responsible for the suppression of TLR-initiated signaling cascades. Biosynthesis of a number of outer membrane proteins and fimbriae is facilitated by the protein encoded by surA, which is a periplasmic cis-trans prolyl isomerase [66, 67].
Several epidemiological, serological, and bacteriological studies revealed that uropathogenic E. coli is the pathogen most frequently associated with UTIs. In recent years, our understanding of virulence factors and behavior of this pathogen is increased remarkably. Several studies showed that E. coli colonizes the urinary tract and may ascend toward the bladder to cause cystitis. If it is left untreated, UPEC may ascend the ureters to the kidney and establish a secondary infection. Our increased understanding of its virulence factors can uncover novel approaches to control UPEC-mediated UTIs. However, accumulation of theoretical knowledge through virulence studies allows practical applications and may facilitate the application of more precise approaches in phenotypic or molecular diagnosis and epidemiology.
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She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. 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