Equations used in the analysis of kinetic energy dissipation.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5517",leadTitle:null,fullTitle:"Hemorrhagic Stroke - An Update",title:"Hemorrhagic Stroke",subtitle:"An Update",reviewType:"peer-reviewed",abstract:"The present book Hemorrhagic Stroke - An Update includes the updated information for professionals who are involved in the management of spontaneous intracerebral hemorrhage. This book contains detailed information about the pathophysiology of spontaneous intracerebral hemorrhage, neuroimaging approach in intracerebral hemorrhage, how to go about surgical intervention decision-making in these patients, and the rehabilitation issues in acute care and in long-term survivors. I hope that the collective contribution from the experts will make this book a valuable guide to further develop their understanding about spontaneous intracerebral hemorrhage. I am grateful to all the authors who have contributed their tremendous expertise to the present book and to my wife and daughter for their passionate support, and last but not least, I wish to acknowledge the outstanding support of Ms. Romina Skomersic, Publishing Process Manager, InTech Open Science, Croatia, who collaborated tirelessly in crafting this book.",isbn:"978-953-51-3522-7",printIsbn:"978-953-51-3521-0",pdfIsbn:"978-953-51-4629-2",doi:"10.5772/63253",price:100,priceEur:109,priceUsd:129,slug:"hemorrhagic-stroke-an-update",numberOfPages:80,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"33690ae286c58afffac09491a13b3a29",bookSignature:"Amit Agrawal",publishedDate:"October 4th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5517.jpg",numberOfDownloads:7932,numberOfWosCitations:1,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:3,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 10th 2016",dateEndSecondStepPublish:"May 31st 2016",dateEndThirdStepPublish:"November 30th 2016",dateEndFourthStepPublish:"January 3rd 2017",dateEndFifthStepPublish:"March 15th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"100142",title:"Prof.",name:"Amit",middleName:null,surname:"Agrawal",slug:"amit-agrawal",fullName:"Amit Agrawal",profilePictureURL:"https://mts.intechopen.com/storage/users/100142/images/system/100142.jfif",biography:"Dr. Agrawal completed his neurosurgery training at the National Institute of Mental Health and Neurosciences, Bangalore, India, in 2003. He is a self-motivated, enthusiastic, and results-oriented professional with more than eighteen years of experience in research and development, as well as teaching and mentoring in the field of neurosurgery. He is proficient in managing and leading teams for running successful process operations and has experience in developing procedures and service standards of excellence. He has attended and participated in many international and national symposiums and conferences and delivered lectures on vivid topics. Dr. Agrawal has published more than 750 scientific articles in various national and international journals. His expertise is in identifying training needs, designing training modules, and executing the same while working with limited resources. He has excellent communication, presentation, and interpersonal skills with proven abilities in teaching and training various academic and professional courses. Presently, he is working at the All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.",institutionString:"All India Institute of Medical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"8",institution:{name:"All India Institute of Medical Sciences",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1029",title:"Hemorheology",slug:"hemorheology"}],chapters:[{id:"56215",title:"Introductory Chapter: An Introduction to Hypertension-Related Intracerebral Hematomas",doi:"10.5772/intechopen.70048",slug:"introductory-chapter-an-introduction-to-hypertension-related-intracerebral-hematomas",totalDownloads:1180,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Ravi Dadlani and Amit Agrawal",downloadPdfUrl:"/chapter/pdf-download/56215",previewPdfUrl:"/chapter/pdf-preview/56215",authors:[{id:"100142",title:"Prof.",name:"Amit",surname:"Agrawal",slug:"amit-agrawal",fullName:"Amit Agrawal"}],corrections:null},{id:"53545",title:"Intracerebral Hematoma",doi:"10.5772/66867",slug:"intracerebral-hematoma",totalDownloads:1454,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Intracerebral hematoma occurs in about 35/100,000 population and the incidence is likely increase over the next few decades as the population ages. The most common causes are hypertension and amyloid angiopathy. Bleeds due to these two causes are classified as primary while all other causes, such as AVM bleeds, coagulopathies, and so on, are classified as secondary. Primary tissue damage due to the intracerebral hematoma is followed by edema, neuronal damage, and secondary damage due to cellular breakdown. Basal ganglia are the most common site of intracerebral hemorrhage, accounting for nearly 50% of cases. CT scan, CT angiogram, DSA, and MRI are the investigations of choice. The initial management is medical, with control of blood pressure and antiedema measures forming the mainstay of treatment. Surgical option includes external ventricular drainage, endoscopic evacuation of hematoma, craniotomy and evacuation of hematoma, and decompressive craniectomy and is usually reserved for patients who deteriorate while on treatment.",signatures:"Shankar Ayyappan Kutty",downloadPdfUrl:"/chapter/pdf-download/53545",previewPdfUrl:"/chapter/pdf-preview/53545",authors:[{id:"191385",title:"Dr.",name:"Shankar",surname:"Ayyappan Kutty",slug:"shankar-ayyappan-kutty",fullName:"Shankar Ayyappan Kutty"}],corrections:null},{id:"54419",title:"Surgical Management of Intracerebral Hemorrhage",doi:"10.5772/67633",slug:"surgical-management-of-intracerebral-hemorrhage",totalDownloads:1854,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Intracerebral hemorrhage (ICH), defined as bleeding within the brain parenchyma, remains a challenging and controversial neurosurgical entity to treat. ICH has a broad range of etiology—stemming from complications associated with traumatic head injury to complications of hemorrhagic stroke. The role of medical management lies in optimizing blood pressure and intracerebral pressure, preventing secondary injury from complications of the hematoma such as seizures, and correcting coagulopathy. Given the mass effect of a hematoma and the possibility of expansion, surgical interventions attempt to evacuate the clot to restore normal intracerebral pressure and prevent worsening neurologic injury. This chapter reviews the recent controversy associated with surgical evacuation of intracerebral hemorrhage placing particular emphasis on the size and location of the hemorrhage and the methods used to evacuate the expanding ICH. Moreover, this chapter reviews considerations and therapeutic goals of the preoperative and postoperative window to minimize complications and optimize patient care.",signatures:"Arvin R. 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Neuroimaging forms the mainstay in diagnosis, which has resulted in improved treatment outcomes. The mandate of neuroimaging includes management, risk assessment, prognostication, and research. This involves rapid identification not only to direct treatment but also to discover the underlying etiology such as vascular malformations or tumors, monitor the evolving course of the hemorrhage and rapidly identify complications. While computed tomography (CT) remains the imaging of choice to rapidly detect acute hemorrhage, growing evidence shows that magnetic resonance imaging (MRI) is comparable to CT for detecting blood in the immediate setting and superior in this regard at subacute and chronic time points. Several advances have been made in the image sequencing protocols to detect bleeds at varying time points and to distinguish possible etiology. Initial and serial imaging is used to identify patients who may benefit from intervention. Advances in this field such as diffusion tensor imaging and functional MRI are being studied for their impact in understanding the extent of injury and possible recovery mechanisms, possibly allowing prognostication for patients.",signatures:"Shazia Mirza and Sankalp Gokhale",downloadPdfUrl:"/chapter/pdf-download/54001",previewPdfUrl:"/chapter/pdf-preview/54001",authors:[{id:"189064",title:"M.D.",name:"Sankalp",surname:"Gokhale",slug:"sankalp-gokhale",fullName:"Sankalp Gokhale"},{id:"189066",title:"Dr.",name:"Shazia",surname:"Mirza",slug:"shazia-mirza",fullName:"Shazia Mirza"}],corrections:null},{id:"56777",title:"Intracerebral Hemorrhage: Issues in Rehabilitation",doi:"10.5772/intechopen.70586",slug:"intracerebral-hemorrhage-issues-in-rehabilitation",totalDownloads:1464,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"While the advancements in the management of the spontaneous intracerebral hemorrhage (SICH) have resulted an increase in survival, this has also resulted in the number of survivors with significant functional morbidity that require long-term care and rehabilitation services. SICH can lead to various impairments, and the deficits related to SICH may include impairment in motor and sensory functions, emotional labiality, language dysfunctions, perception deficits and cognitive dysfunctions. 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\r\n\tThe scope of systemic family therapy differs and encompasses cross-cutting contemporary issues related to clinical health, disaster, humanitarianism, displacement, migration, sexuality and reproduction, sexual orientation and gender identity, conflict, and socio-economic concerns. This book, therefore, aims to provide readers with a comprehensive overview of the current state-of-the-art advances in counseling and psychotherapies for families and couples in functional and dysfunctional settings, crisis settings, humanitarian zones, conflicts, and disaster settings. It aspires to showcase scholarly work on the practice of family systemic therapies by researchers, students, professionals, and trainees. The goal of this book is to further explore recent advances, new perspectives, and applications of systemic family therapies on issues such as basic concepts and tools, basic therapeutic skills, the therapeutic process, predominant models of family therapy, the principles of using a constructive and collaborative approach that enhances family resilience and competence in disaster-prone areas. The book will be a collection of scholarly writings on strengths-based therapies and contemporary models such as solution-focused, narrative and conversational therapies for family relationships.
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Guidance and Counselling (1999)from the University of Ibadan, Nigeria as well as a B. A. Hons English Studies (1987) from the University of Ife, Ile-Ife, Nigeria. She also had professional training in Gender Perspectives in United Nations Peacekeeping Operations (2009), Civil-Military Coordination (CIMIC) (2009), and Global Terrorism (2009) under Peace Operations Training Institute, Dispute and Conflict Analysis (2007), and Gender and Health (2013) at AMREF in Nairobi, Kenya. She is currently working at the Centre for Gender, Humanitarian and Development Studies, Redeemer’s University, Ede, Osun State, Nigeria Ado-Ekiti as a Reader. She has an enthusiastic and flexible approach to teaching and a commitment to research and publication. 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In industry, some of the energy dissipation mechanisms and phenomena that accompany projectile impact environment-specific materials are still unknown. In order to advance the development of materials or focus on the protection of these eventual systems, it is important to take steps to identify environmental problems, to advance the possibility of effective impact protection solutions using known materials, using research like this, but with effective collaboration to develop solutions and further reducing noise by lack of resources. It is necessary to obtain collaboration of several entities, such as state and university-industry scientific and further technological development. The research on ballistic protection has restricted nature; due to the qualification of the subject as strategic, it is necessary to continue in these strategic research for the preservation of life, and the use of high-tech materials, call the research the development of materials that have a minimal negative impact on the environment, which would be a second function of protecting life.
\nA protection system emerges as an assembly of components where each has its own functions to protect an item or human being through the absorption of kinetic energy derived from direct or indirect collision with a projectile. Systems can be flexible, formed by rigid or polymer fabrics or metals, or ceramic plates and rigid polymers. Systems can be formed by various materials as sandwich panels; an example applied is usually illustrated in Figure 1. The penetration mechanism is shown in a system designed by a combination of plastic, center of ceramic material, with a backrest-purpose flexible application–specific protection material.
\n\nThe polymers have been occupying spaces where metal and ceramic materials were predominant, now in response to the need for mass reduction, polymeric materials have applications in light protection such as suits, military [1] hardware, and rigid applications in specific parts of helicopters and land vehicles. Compounds systems aim at combining the properties of individual resistance of each material to obtain a higher property required. In recent years, with the ultrahigh molecular weight polyethylene (
Composite panel (1, polymer; 2, ceramic flexible; 3, backing).
The selection of materials was made from knowledge of the properties of polymers and ceramics used in ballistic applications [5–8]. Silicon carbide (SiC) was selected as the ceramic material because of the high hardness, high abrasion resistance, and its history in ballistic applications [9], besides being a commercial ceramic. The properties of SiC are due to the type of atomic bonding and crystalline structure hexagonal designed that cubic form α– SiC, the structure obtained depend on the method used for their production; in this case, the powder of silicon carbide used is produced by the Acheson process, which involves the reduction of silica sand in contact with petroleum coke or anthracite to a temperature close to 2400°C for 36 h, to form the commercial grade SiC α [10]. The properties of the ceramic used are as follows:\n
Grain size: 10–50 μm
Purity of material: silicon 80%, 20% silica binder based on cellulose apparent porosity of 40%
Average true density: 1.60 g/cm3, obtained by making direct mass and volume of samples
Temperature: 1250°C
Plate dimensions: 197 ± 197 ± 3 mm × 3 mm × 5 ± 1 mm
Average mass of plate: 293.4–312.9 g
Theoretical density of SiC: 3.1–3.2 g/cm3 [11]
Color: green
Composed of compaction at atmospheric pressure, subsequently sintered in an electric furnace at 850°C
Morphology of the ceramic plates.
To determine the porosity of the samples, initially the specimens were dried and sintered in an oven at 850°C, then these were tested according to the ASTM C1039 standard for the apparent porosity of 40%; the surface porosity of the plates was 46% obtained using image analysis software. Image A in Figure 2, the plate obtained is shown unmodified, exhibits the surface porosity resulting from compaction process. Image B is observed at the surface of the plate with epoxy resin coating after dipping process, the isometric view. In image C, a portion of the plate with magnification 100× microscopy, where the resin has achieved infiltration into the porous body thereof, image D, as can be seen to the shaped plate bodies, is observed to be adhered to the polyethylene sheet (UHWMPE).
\nThe flexible material selected for the system embodiment was laminated fabric of ultrahigh molecular weight polyethylene (UHMWPE) given the properties of high kinetic energy absorption in ballistic protection systems published in the current literature. In Figure 3, the morphological composition of the panel, in which each of the layers consisting of parallel threads, in the configuration of two successive layers in the same orientation panel is observed; the next two layers are oriented perpendicularly to the direction of previous threads. In Figure 3, image A, the panel is illustrated with an impact recording, seen isometrically. In images B and C, the panel approach is illustrated; it is evident that the diameter of each wire was about 18 μm and the size of the fabric to the development of the system was 200 mm × 200 mm ±3.
\nImages polyethylene ultrahigh molecular weight used.
The adhesive used in exploration is epoxy resin due to its good response, good heat sink residual stress, and compression stress [12], with better properties than polyester or phenolic resins have high hardness and very good adhesion in inhomogeneous materials [13]. Some of the properties of the epoxy resin used in this work are as follows:
\nDensity: 1.1–1.4 g/cm3.
\nGlass transition temperature: 120–190°C.
\nViscosity: 113 centipoise at 22°C, viscosity taken in laboratory viscometer Brookfield of the Instituto Tecnológico Metropolitano, Medellin, Colombia. Main features are as follows: low shrinkage, good mechanical performance up to 180°C, good chemical resistance, high wear resistance, and high crack resistance.
\nAs a destructive testing protocol, Ballistic Resistance of Body Armor NIJ Standard-0101.06, Section 4.2.1.2 [14], where the configuration of ballistics test is conditioned, is considered. In Figure 4, the graphical representation of the assembly for performing the impact test is observed. In Figure 5, the projectile used is shown, in side view, according to the standard for conducting the tests.
\nAssembly required for testing ballistic impact, NIJ standard.
Longitudinal dimensioning of the projectile used.
For the characterization of the mechanism fault at macrometric scale, a calliper gauge to measure the diameters of the input crater and the output crater cone formed in the flexible phase of the system was used. To observe the cross section of a system, hydrocutting was used and the impact zone was analyzed, and to observe the details in the deformations through optical microscopy, the results are presented in the following sequence.
\nTo manufacture the laminated composite systems the following process was carried out: they were placed, plates and sheets organized by polyethylene, in a cubic container that contains enough volume to be immersed in the epoxy resin, which was poured manually. The curing process of the resin is carried out at a room temperature of 19–25°C with a time period of 24 h because there it was recommended to use furnace having ceramic covered surface plates with epoxy resin; and the process contraction of the resin may crack the plates.
\nAs a response variables to the impact factors such as diameters generated (input, output, and plastic cone on flexible material) are considered. In Figure 6, designs for impact analysis are shown. Group A (see from right to left) corresponds to the arrangement of the system with main layer receiving the projectile in woven polyethylene with ceramic backing and group B (see from left to right) corresponds to the arrangement of the system with main layer receiving the projectile in ceramic-backed polymer fabric. To perform the ballistic test for each impact system and perform characterization using optical microscopy, the samples were selected randomly to observe the predominant interaction in each of the systems.
\nImpact sides. Direction side A: impact through UHWMPE; direction side B: impact through ceramics.
In this case, the experiment was carried out placing the ceramic plate and receiving the metal projectiles, which were obtained with different morphology of some fractures as cited below. The bullet entered forming a crater that eroded an area of ≈3 mm around the crater and it is recalled that the initial diameter of the projectile was 9 mm. In Figure 7, drilling obtained as a result of the impact is illustrated in the left panel, the image formation of five cracks with perpendicular impact is illustrated in the right image; such fractures that move only by the surface plate without presenting complete rupture were observed. Possibly the presented erosion was due to the deformation process of the projectile, whereas the drilling system was due to their characteristics that greater drag is not imposed as a result if a large number of traces are drilled. The highlighted panel is uniform along the axial symmetrical quasierosion drilling.
\nFootprint of the projectile on the ceramic plate.
The footprint of the projectile after passing through the system, the flexible fabric material ultrahigh molecular weight polyethylene, important evidence deformations caused by the moving projectile, and fractures shown are reflected in these images.
\nImages to backing fractography.
The isometric view of the composite system is observed in Figure 8. The overall damage done by projectile in the material can be seen in image A; an approach breakage of the fibers is shown in image B, along with the tag marked with red arrows in the footprint direction taken by transverse waves, which end with the formation of a neck in the laminate plane (image D), total rupture of the primary fibers that come into direct contact with the projectile, fracturing the flexibility scheme delamination near the area impact. The deformation of the polyethylene layers results in a 12 mm high cone, with almost 40 mm base diameter and 18 mm in the outlet of the projectile; the fiber tear around the hole and image B together with the cone can be seen; deformation caused to the projectile as a result of the penetration process.
\nOutput of the projectile.
Figure 9 shows the formation of a neck (necking) in the laminate plane, the total disruption of the primary fibers that come into direct contact with the projectile; the projectile completely passes through detailed, they deform the polyethylene layers forming a 12 mm high cone with resulting delamination process with cross section of the projectile on the system; the deformation petals on the flexible layer is called petaling.
\nFigure 10 shows the location of the plates and the direction of impact test that was obtained after subsequent analysis of fractography.
\nIn Figure 11, as shown from top to down, the plate is in isometric view, where the penetration hole of the projectile, in image A, shows the detailed view with increased detail in which the crater is formed with broken fibers, the shearing caused tissue and adjacent tissues delamination of the crater. Image B is observed, twisting and fusing the fibers as the result of mechanisms present after impact stress, image C is detailed in the image cutting and twisting the fibers of polyethylene during ductile voltage departure.
\nProjectile input direction side A, impact thought UHWMPE.
Fractography in the projectile output zone.
In Figure 12, the fractography of a system receiving the projectile double ceramic plate that is 10 mm thick and double back sheet flexible polyethylene is shown; image A is highlighted by the mark left by the projectile detailed, which enters flexible face with a hole diameter of the projectile (9 mm), greater penalties, and the rear face forming a crater that is eroded in an inhomogeneous way around the inlet port, cracks occur, which travel only by presenting external ceramic plate breakage. Rupture plates with crater formation in stages with the passage of the projectile are observed. The geometry of the crater [6, 15, 16] has formed in the radial symmetry breaking evenly.
\nFractures and cone on the plate “Backing”.
In Figure 13, a frontal approach presents originated crater, streaking in the resin layer with a radial direction and erosion on the area near the impact surface is highlighted. The strain energy breaks the crater forming cracks from the edge to the back of the panel, which travel through the ceramic material, the breakage of fibers near the orifice, and close to delamination contact area.
\nCrater originated in the double ceramic plate.
In Figure 14, the morphology of the system in cross section cab be observed, which was created using water jet cutting. The image in the input direction of the projectile, which originated a large area delamination and spalling inside the plate, and in the radial direction of the projectile is observed. It is observed that vacuum is created conically. Interlayer resin deformation only in the input diameter of the projectile in the plate target can be seen; it can be ensured that achieving attenuate kinetic energy, which is distributed in the ceramic plates, meaning through spalling, but without stopping the projectile, shows that the resin layer remains intact and shows good adhesion with the ceramic. It can be stated that the ceramic dissipates energy with the formation of the crater, along with the flexible system, which is seriously affected.
\nFractography cross-sectional view.
Fractography double cross view on the ceramic plate.
In Figure 15, some failure mechanisms as spalling between the ceramic layers and the resin layer can be seen in cross-section, which can be realized as the intraseparation and interlaminar ceramic where the fracture material arrangement similar to leaves is superimposed without total detachment. Also, the crack initiation deforming plate from contact with the projectile is observed traveling environment symmetrically radial through the complete system. Some fractures travel lengthwise through porosity ceramic into contact with the gaps or vacancies in the resin layer, which ends up slowing the advance of the fracture plate in the bottom plate continuous plastic deformation with continuity conical-shaped crater to the total output of the projectile, with the red arrow penetrating the sense indicated.
\n\nA detail of the cross section of image A spalling is illustrated in Figure 16, which is mentioned in the previous paragraph describing environment puncture by the displacement of the plates; this dislocation of the solid layers is possibly the result of the trip transverse waves of energy during the compression exerted by the projectile. The eroded layer is the result of pressure and high temperature as a mark left by the passage of the projectile during contact with the ceramic plates. In image B, the detailed projectile outlet and a portion of tissue shearing during impact stress as observed drag is shown.
\nDetail of the passage of the projectile by the ceramic body.
In Figure 17, a trace of the passage of the projectile, which crosses the plate, causing a crater with a diameter greater than the projectile penalties, erosion causes environment entry system, leaves a marked trace of the shear wave, is observed as deformation caused by high contact temperature and the velocity of the projectile, which dissipates some of the kinetic energy in the radial cracks from the impact point.
\nIn Figure 18, the footprint on the plate epoxy resin is shown in detail in image A, the projectile enters the plate melting the resin perimeter of hole, and waves are formed due to the rapid solidification of the material before the passage of the projectile with high temperature. In image B, the morphology of details of one of the waves and the rough texture caused by the process of rapid cooling of the material is observed. In image B, the crater is observed and chipping caused in the layer of flexible polyethylene is shown, which solidified with resin around the crater erosion caused in response to the opposition of the material passage of the projectile.
\nFootprint of the projectile on the layer epoxy resin.
Footprint waves on the layer of the epoxy resin.
In Figure 19, the result of the impact on a plate of silicon carbide with 5% porosity is closely illustrated; it was manufactured by means of high pressure and temperature. In image A, a view of the isometric plate is generally observed, in which in the center the product of impact deformation can be seen, with the distribution transverse cracks the crater. In image B, the front view of the crater on the ceramic plate is observed in the joint caused by shear waves that completely fractured ceramic cracks. In image C, the center of the impact is displayed, which completely distorts the projectile, completely dissipating the kinetic energy, and the fracture was complete. The silicon carbide plate was very efficient, it was observed that totally absorbed kinetic energy of the projectile, the plate with geometric characteristics and low porosity compared to original plates, was used in the exploration, whereas the rear layer of polymeric fabric did not present deformation and remained intact against impact, worked to contain remaining fragments of ceramic originating from direct contact with the projectile.
\nFractography in the ceramic plate with reduced porosity.
The failure mechanisms generally observed in this exploration have been reported, a brief description of different types of failure is presented below. The formation of a crater followed by crack propagation is reported in the rigid ceramic systems; Horsfalla et al. [17] and Medvedovski et al. [18] found that it was also possible to identify the individual component in a compound system with different functions during the deformation of the panel in these publications and that the form of energy dissipation also depends on the materials and the manufacturing processes. The compaction process and pressing of ceramic powders determine the porosity in the final product, with these processes it seeks to maximize the mechanical protection systems with high-capacity energy dissipation properties, characteristic involves reducing the porosity at least; the pores are small defects that may act as stress concentrators and initiators for material failure [19].
\nIt has been found that the composite systems surpass the dissipation of energy capacity; at the conventional systems used without any combination, Sherman and Brandon [20] detected a sequence in the mechanisms of energy dissipation in a ceramic plate, such as the formation of radial cracks during traction associated with this downward tensile strength of ceramics. Cunniff et al. [21] presented the performance of ballistic polymer fiber; they also identified the mechanisms of fracture in flexible fibers and its potential energy absorption. In the flexible system, another predominant mechanism in tissue polymers during the dissipation of kinetic energy is the formation of a conical pyramid backing material; it was observed that the strain and deformation are function of the distance of the impact; therefore, the wires are closer, experience stress failure, whereas the most distant point of impact wires have no tension [22].
\nThe basis for the model applied to the evaluation of these analyses was developed by Morye et al., being the most similar characteristics presented for the study [23]. This model analyzes the tensile failure of the primary fibers, elastic deformation of the secondary fibers, delamination, breakage of the system matrix, and the formation and movement, which are five deformation mechanisms that contribute to the dissipation of energy from the projectile and are considered a cone on the rear side of the plate of the composite. The five energy absorption mechanisms that were applied are as follows:
\n\n | ||
---|---|---|
Explained in the previous paragraph | \nEq. (1) | \n|
E is the difference between the initial and residual kinetic energies, this corresponds to the energy lost by heat and deformation during impact is calculated as follows (Eq. (3)) | \nEq. (2) | \n|
of the projectile, and | \nEq. (3) | \n|
The additional kinetic energy ( lost through deformation during drilling due to the presence of the circumferential cutting zone | \nEq. (4) | \n|
rear face of the composite plate and is determined by Eq. (5) | \nEq. (5) | \n|
thickness | \nEq. (6) | \n|
\n | Eq. (7) | \n|
ET = | \nEmpiric equation used for this exploration | \nEq. (8) | \n
Equations used in the analysis of kinetic energy dissipation.
The total energy absorbed by the laminate composite in Eq. (1): where EFP is the energy absorbed by the failure of the primary fibers; SAI, energy absorbed by the elastic deformation of the secondary fibers; EKC, energy absorbed in the formation and movement of the cone at the rear face of the panel; EDL, energy absorbed due to delamination of the material; ERM, energy absorbed due to breaking of the matrix.
\nAnother model studied was presented by Retch and Ipson [23, 24]; they presented a semiempirical model where a balance of kinetic energy is analyzed and the energy is dissipated by the generation of the crater during the impact (Eqs. (6) and (7)). For the study of energy, balance takes into account the following characteristics of the composite system: mass, density, and dimensions of the system; mass, diameter, and velocity of the projectile; and residual impact velocity and mass of the plug (product ejected by impact); the energy balance formula is presented in Table 1.
\nDouble flexible fabric in front and ceramic double plate as backing | \nCrater formation on ceramic backing, ductile fracture in the fibers, defibrillation | \n||||
Ceramic double plate in front and double Flexible fabric as backing | \nLow crater formation on ceramic backing, fracture in he fibers nearly to crater and conic formation on the UHWMPE backing | \n\n | |||
Ceramic plate with less porosity Single in front and double Flexible fabric as backing | \nCrater formation on the ceramic plate with multiple fracture, neither deformation in the backing face. | \n\n |
Results of kinetic energy dissipated.
The analysis complemented with the study of flexible and rigid systems, abstracted to empirical analysis, modeling the energy absorption by the mechanism of formation of the cone on the rear side of the laminate, whose vertices move at the same speed of the projectile (
The fractography found in the ceramic component is defined in the formation of a crater, erosion, and fracture, while the polymer components were observed as mechanisms for energy dissipation, delamination, cone formation, petals, breakage, and melting fibers.
\nA large number of failure mechanisms were observed in the design sandwich double ceramic plate in the front and double sheet of UHWMPE in the back; they were observed as dissipation mechanism energy, fragmentation and erosion on ceramic plates, forming petals, delamination and cuts in polymer sheets; these evidences in the photographs were indispensable data for the analysis of kinetic energy dissipation using the semiempirical models of Reich and Ipson and Morye et al.
\nIn this exploration, it was possible to observe the influence of the manufacturing process in a system of high requirements in terms of dissipation of kinetic energy, which is why the analyzed total dissipation of energy system was obtained by high pressure and high temperature of case C as compared to cases B and C, which were manufactured by traditional techniques.
\nThe authors specially thank to Knight Group Owners Caballero SAS International, headed by the CEO engineer Miguel Caballero, for their decisive collaboration, disposition, and financing of ballistics tests, laboratories and polymeric material. They also thank the company Quimiresinas for its contribution in the epoxy resin and to the Universidad Nacional de Colombia, Medellin, at the laboratory metallography and materials testing by providing resources for the acquisition of most of ceramic plates used in this exploration. Acknowledgments in memory to Military Engineer Edgar Caicedo for was showing me the way of success in the Engineering Design.
\nThe prostate gland is the only accessory sexual gland in the male dog. Some authors in addition name the ampullae ductus deferentes. The canine prostate secretion is a transport medium among others for passive transportation of the spermatozoa into the uterus during ejaculation. The prostate secretions furthermore influence the motility and function of the semen cells; the exact composition and many functions are not yet known and vary dependent on the laboratory and the analysis method used [1]. The composition of mineral nutrients, as well as the amount of cholesterol, albumin [2], zinc-binding proteins [3], fertility-associated proteins like osteopontin [4], the antioxidative capacity [5], and many more have been examined. A new study investigated the composition of the seminal plasma by use of mass-spectrometry [6].
Diseases of the prostate gland frequently occur in aging dogs [7, 8]; the incidence increases with age: 6.2% in intact males with ≤ 4 years, 17.5% in 4–7 years old dogs, 32.8% in 7–10-years old dogs, and 43.5% in male dogs >10 years of age [9, 10]. Diseases of the prostate gland can be infectious or noninfectious. In aging dogs, the noninfectious benign prostate gland hyperplasia (BPH) is the most frequent disease, occurring in 80% of all intact male dogs older than 5 years and in >95% of male dogs older than 9 years [11, 12]. The BPH can be easily treated; however, the disease will become chronical with regular rezidives and only castration will finally cure the dog. Inflammatory diseases may be chronical or acute; the acute prostatitis is mostly caused by bacterial infections, either ascending via the urethra or via the bloodstream. The chronical prostatitis develops from a BPH or an acute prostatitis if treated with wrong antibiotics or for a too short period of time [7]. Highly effective antibiotics applicated for a sufficient period are essential for the successful treatment of the prostatitis.
The squamous metaplasia develops due to hyperestrogenism occurring because of endocrine testicular tumors; however, may also be caused by estrogen applications [8].
Prostate tumors are relatively rare in dogs, the incidence is on average 0.43% [13], they mainly occur in older dogs and more frequently in castrated than in intact dogs; the growth is not androgen-dependent [14, 15, 16]. In this chapter, modern diagnostics and therapeutical methods are discussed.
The aim of each treatment must be, to hinder the development of chronical diseases, for prevention of the long-term use of antibiotics that are needed for special infections [17]. Regular examinations, best starting when the dog reached 40% of life expectancy, will help to reach this goal [18].
This article provides an overview of diagnostical and therapeutical measures in different prostate gland diseases and insights into at present most actual developments.
The canine prostate gland consists of two parts, surrounding the caudal part of the urethra; it is round to oval and has a sulcus dorsal and ventral that can be reached by digital rectal palpation. It is surrounded by a thick fibro-muscular capsule releasing septs of smooth muscle tissue into the gland. The urethra is situated in the middle of the prostate gland and between the two parts. The situ of the gland is dependent on age; in young dogs, it is situated in the pelvis, in aging dogs more in the abdomen, and because of an increasing size of the diseased gland, in the old dog, it can be situated in the pelvis again. In this case, it can be examined by digital-rectal palpation again. The cranio-dorsal and cranio-ventral part of the gland is covered by peritoneum. The glandular ducts open into the urethra at the site of the pars disseminata and on the colliculus seminalis. The blood supply is provided via the arteria pudenda interna, innervation by the hypogastric nerve [19].
The prostate reaches maximum secretory activity in dogs of on average four years of age [20], the secretions comprise >90% of the ejaculate; the gland continues to grow under the influence of testosterone because of stem cell differentiation, and in the aging dog will increase in size because of hypertrophy and hyperplasia. Growth and secretion are regulated by the active metabolite of testosterone (T), namely the 5α-Dihydrotestosterone (DHT). More than 95% of testosterone are converted into DHT by the enzyme 5α-reductase, after diffusion into the prostate gland cells. DHT binds stronger to the testosterone receptor than T [21, 22]. Estradiol-17ß supports the effect of DHT in a synergistic way and, in addition, causes an upregulation of testosterone receptors [11].
The prostate gland secretion supports the transport and the function of spermatozoa after ejaculation. It contains citrate, lactate, cholesterol, and enzymes; however, few sugars and phospholipids are supposed to provide additional energy. The composition of the prostate secretions was recently investigated by means of proteomics [6, 23]. The serine-protease canine prostate specific esterase (CPSE) and the lactotransferrin-precursor are the most frequently occurring proteins in the seminal plasma [23], comprising 90% of all proteins. The CPSE has a proteolytic effect, similar to chymotrypsin [24] and after binding influences spermatozoa function by its zinc-binding properties [3]. The CPSE binds to phosphorylcholine-binding protein and choline phospholipid of the membrane and induces the efflux of cholesterol from the spermatozoa membrane during ejaculation, which is essential for capacitation. The secretion of CPSE is controlled by androgens [25] and the enzyme is believed to be a reliable marker of prostate secretion [26].
The extracellular matrix of the canine prostate (noncellular stroma and fibrous tissue) supports the development of the gland and the control of cellular functions [21], supposedly via cellular transmitters like cytokines [27].
This noninfectious disease of the prostate gland only occurs in intact male dogs with endocrinally active testicles. The disease counts for 50% of all prostate diseases [9]. The incidence increases with increasing age; however, in rare cases, BPH can occur at the age of 2–3 years [28]. Sonographical and in part clinical symptoms usually can be seen in 80% of male dogs at the age of 5 years [11, 12, 20], and in >95% of males at the age of >9 years [11]. The hyperplastic increase in size is caused by:
A change in steroid-hormone-concentrations
An increasing estrogen: testosterone ratio in the intact, aging dog [29]
A change in the receptor expression within the gland and especially by increasing concentrations of DHT in the epithelial, hyperplastic tissue.
Dihydrotestosterone is the active form of testosterone and produced from testosterone by the enzyme 5α-reductase. The activity of the enzyme increases in the aging dog, especially in the glandular epithelial cells; therefore, the hyperplasia mainly concerns the glandular epithel and less the stroma [30, 31]. In one experiment, BPH could be produced by long-term application of 5α-androstan-3aα, 17ß-Diol (3α-Diol), in combination with 17ß-Estradiol. 3α-Diol is produced by reduction from DHT and/or 17ß reduction from androsterone; it stimulates the intracellular cAMP production in the prostate gland [32]. In another experiment, the testosterone concentration was doubled on days 21 and 42, with the same effect [33]. The experiment points toward the impact of these hormones and an eventual change in the enzyme and metabolic activity inside the aging gland. The role of local growth factors and relaxin is still not sufficiently investigated.
Prolactin was detected in prostate secretions of dogs with BPH and with higher concentrations than in healthy dogs; during the development of the prostate, prolactin contributes to growth and differentiation [29].
As a further predisposing factor, the breed was previously mentioned; large breeds seem to be more often concerned [34, 35, 36] and in a recent study, the Rhodesian Ridgeback was shown to be predisposed, pointing toward a genetic cause (Werhahn Beining et al. 2020). Some authors suggest a breed-specific pituitary prolactin secretion, which lacks evidence so far but deserves better investigation [35, 37].
The disease starts with centrifugal increase in size; sonographically, changes in echogenicity and cystic caverns become visible. Clinical symptoms develop later on [18]. Therefore, the BPH can be termed a physiological process in aging dogs, until clinical symptoms occur (Tsutsu et al. 2000).
The first clinical sign mostly is serosanguinous preputial discharge not associated with urination; this discharge occurs because of vessel damages in the hyperplastic, well-perfused tissue [38].
The secretions reach the urinary bladder via the pars disseminata causing a bloody admixture of the urine [9, 38]. In breeding dogs, a changed composition of the prostate secretions causes an increase in pH, a decrease in motility, and bloody prostate secretions [39, 40]. Later on, morphological aberrations of spermatozoa occur [19]. BPH may cause reversible infertility. Abdominal pain because of the enlarged gland is seldom [9, 19]. The centrifugal growth of the gland causes compression of the urethra and can cause dysuria, dyschezia, stranguria, and even anuria; however, the latter is seldom [11, 41], and urination problems were seen in only 27% of dogs with BPH in one study [9]. Defecation problems more frequently occur, especially in advanced stages of BPH due to compression of the rectum, leading to acute constipation in extreme cases [19, 42].
For an accurate diagnosis, a case history, a clinical-andrological examination of the dog including digital rectal palpation and abdominal sonography are obligatory. Furthermore, examination of urine and semen, as well as cytological examination of the prostate gland secretions can be helpful. Zambelli et al. [43] used the parameters anorexia, loss of weight, degree of tenesmus and dysuria, urinary incontinence, preputial discharge, and hematuria for clinical grading of the BPH in 4 grades, with grade 1 corresponding to asymptomatic BPH.
Digital-rectal examination reveals a symmetric increase in size, normal consistency, and no painfulness; large intraprostatic cysts may cause asymmetry [38].
Sonography (B-mode) of the physiological prostate. Prostate gland of a healthy 5-year-old beagle, the white arrows mark the contour. The size was 3 × 2 cm (L × W), the structure of the gland is homogenous, the echogenicity is physiological, and the anechoic line in the middle is the urethra.
The volume of the gland correlates with the body weight [47] and can be calculated when length (L), width (W), and height (H) were measured by using a formula; for example,
Measured L × W × H × 0.523/estimated volume (0.33 × body weight in kg × 3.28).
In dogs with BPH, this ratio will be > 2.5 [48].
With B-mode sonography, the prostate with BPH appears enlarged, and the parenchyma is homogenous and hyperechogenic. Intraprostatic cysts of different sizes are frequent (Abb.3), and paraprostatic cysts sometimes occur [8, 12, 18, 45] (Figure 2). Cysts are round, thin-walled structures with anechoic contents and distal increases in echogenicity [45].
Sonography (B-mode) of a prostate gland with BPH.
The prostate is high-grade enlarged (arrows), the structure is homogenous, and the echogenicity is increased. The dog showed bloody preputial discharge, stranguria, and defecation problems.
When using special doppler-sonographical methods like power or pulse-wave Doppler sonography in dogs, the examined vessels [49], as well as previous ejaculations and medications, have to be considered; a sexual rest before the examination is recommended [50]. The case history should reveal whether a gonadotropin-releasing-hormone(GnRH)-analogon was applicated previously, which will change the findings considerably [51].
An increase in perfusion of the gland was recorded in 8/16 dogs with BPH in one study, using pulse-wave Doppler sonography [46]. In another study, peak-systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly higher in dogs with BPH than in healthy controls [52].
Contrast-enhanced sonography (CEUS) proved to be advantageous for evaluation of vascularization and perfusion of the canine prostate gland. For this method, ultrasoundcontrast agents (UCA) are injected intravenously. Unfortunately, the use of different UCA makes results from different studies difficult to compare [45]. In one study, healthy male dogs were injected with a micro-bubble UCA with the aim to obtain physiological reference values [53]. However, one study is not sufficient; the generation of reference values by using a large and comparable data pool, standardized methods, and settings is a big problem.
In an earlier study, micro-bubble UCA and CEUS proved to be useful for detection of vessel damages and necrosis. Unfortunately, it is still not possible to differentiate between BPH and chronical and acute prostatitis, respectively [54]. However, together with further diagnostic methods, these sonographical tools provide worthful diagnostic findings.
Elastography is an interesting tool for evaluation of tissue consistency, the degree of elasticity, and rigidity. The principle is that the degree of deformation after pressure on a certain tissue is inversely proportional to the rigidity of this tissue [55]. Different methods such as acoustic radiation force impulse elastography (ARFI) [56] were evaluated in dogs. With qualitative ARFI, short acoustic impulses of high intensity are used for deformation of the tissue, then the data are converted into a statistic grey scale (Elastogram), revealing the rigidity of the examined tissue. With quantitative ARFI, an acoustic wave is sent in a certain region of the tissue, spreading at a certain velocity within this tissue, and dependent on the rigidity of the tissue. The measured velocity correlates to rigidity and viscoelasticity of the tissue [57]. For examination of the canine prostate gland with elastography, physiological values for different groups of age are available [56, 58, 59]. Unfortunately, no controlled study about the use in dogs with BPH is available. The method requires some training.
Echostructure analysis or computerized histogram analysis of sonographical pictures is a method well-known in human medicine for diagnosis of mammary tumors. Similarly in dogs, the method proved to be useful for the diagnosis of mammary carcinomas [60]. For this method, the gland is examined via B-mode sonography and the pictures are digitalized. Then so-called regions of Interest (ROI) are marked in the pictures (Figure 3) and objectively evaluated by using computer-assisted analysis. (software: for example ImageJ; Wayne Rasband, National Institutes of Health, Bethesda, Maryland, USA) The echostructure analysis provides information about brightness, micro- and macrotexture, homogeneity, and contrast differences within a certain tissue [60, 61]. In a previous study, the echostructure method was used to differentiate between BPH and chronical prostatitis. In dogs with BPH, the homogeneity of the gland tissue was significantly higher than in the dogs with chronical prostatitis [62].
Echostructure Analysis of the prostate gland, regions of interest (ROI).
For the objective analysis of the digitalized, B-mode pictures, four quadrants of equal size have to be placed in the region of interest. The measures are performed automatically in these regions. Evaluation is performed by a special software.
X-ray of the canine prostate gland provides information about the size and situ of the gland. In healthy dogs, the diameter of the prostate is at a maximum 70% of the distance between the cranial margin of the pubic bone and the promontory of sacrum [63], an increase in size points toward BPH. By using a retrograde urethrocystogram, examination of the urethra is possible; the lumen can be confined by BPH, abscesses, or neoplasms [63]. In a previous study, power injection of a contrast medium during retrograde CT-urethrography improved the evaluation of the urethra; dilations of the urethra could be easier evaluated in relation to the degree of the filling of the urinary bladder [64].
Diseases of the prostate gland can be diagnosed by use of
A rather new method is the diffusion-weighted and perfusion-weighted
In case of canine BPH,
A
In dogs, the final diagnosis BPH can only be made by use of fine needle aspiration (FNA); this method should be performed when the dog is sedated and received analgesia. The FNA is done transcutaneously under sonographical control [8, 19]. However, even though providing the final diagnosis, this method is mostly not necessary. The cytologically obtained results correlate well with histopathology. Only for differentiation between chronical prostatitis and prostate gland carcinoma, FNA or biopsy must be performed [66, 72, 73, 74].
Measurement of the canine prostate-specificesterase (CPSE) can be helpful. The concentration of this enzyme in the blood is significantly increased in case of canine BPH and other diseases [29, 33, 48, 75, 76, 77, 78]. Unfortunately, it is not possible to differentiate between BPH, prostatitis, and neoplasia, and the reference values for healthy dogs are variable in the literature [48, 75, 77]. The secretion of the CPSE is age-dependent in dogs, therefore, reference values must be critically considered. The diagnosis BPH should not be solely based on measurement of the CPSE. In one study, a combination of clinical symptoms, CPSE measurement, and calculation of the prostate volume (real volume/estimated volume = V ratio) were evaluated. The clinical BPH coincided with a V-ratio of >2.5 and a CPSE concentration of > 90 ng/ml; the sensitivity was 85% and the specificity 72% [48]. Meanwhile, a commercial assay is available (Odelis® CPSE, Bio Veto Test, Nice, France) and another study revealed a sensitivity of 97.1% and a specificity of 92.1% [79].
When the general condition is undisturbed, BPH can be mistaken for chronical prostatitis or beginning neoplasia in dogs.
Therapy is only necessary when clinical symptoms are visible. When the dog is asymptomatic, regular clinical and sonographical controls every 3–6 months are recommendable [42]. Vets can choose between different medicaments, providing the best choice for a subject [7].
The most effective method is the castration, involution starts within 6–12 weeks [7]. The clinical symptoms will disappear earlier and a decrease in size can mostly be palpated after 1–2 weeks [42]; the volume will decrease to 60% within one week [10], and by 50% after three weeks [39]. Bloody preputial discharge disappeared in 89% of cases within 4 weeks after castration [38]. Castration is the treatment of choice in case of hyperdistention, dyschezia, perineal hernia, or large retention cysts [42].
Table 1 provides an overview of useful and recommendable medicaments against BPH
Agent | Effect | Preparations | Dosage | Application | Decrease in size after (days) | Duration of efficacy (months) | Side effects | Authors |
---|---|---|---|---|---|---|---|---|
Cyproterone-acetate | AntiAndrogen | Injectable (Depot) | 2–5 mg/kg SID (can be repeated after 1 week) | s. c. | 7–14 | 6 | Apathy, thirst, mammary tumors, increase in appetite, loss of libido | [31, 80, 81] |
Tablets | 2–3 mg/kg daily | p.o. | ||||||
Delmadinone-acetate | AntiAndrogen | Injectable | 1–3 mg/kg SID (can be repeated after 1 week) | i. m. | 14 | 6 | Diabetes mellitus, mammary tumors, increase in appetite, loss of libido | [82, 83] |
Osaterone-acetate | AntiAndrogen | Tablets | 0.2–0.5 mg/kg/day (7 days) | p. o. | 7–14 | 6 | Decrease in semen quality, increase in appetite, loss of hair, lethargy | [7, 10, 84] |
Finasteride | 5α-Reductase-Inhibilor | Tablets | 0.1–0.5 mg/kg/day (16 weeks) | p. o. | 30–120 | Dependant on duration of application | - | [12] |
1 mg/dog/day (3–21 weeks) | p. o. | [85] | ||||||
1 mg/kg/day (3 weeks) | p. o. | [42, 83] | ||||||
1.25 mg /dog /day (195 days) | p.o. | [42] | ||||||
Deslorelin | GnRH-Agonist | Subcutaneous implant | 4.7 or 9.4 mg /implant (repeated application possible) | s. c. | 37 | 6–12 | Flare-up within 1 week | [51] |
Medicaments with an antiandrogenic effect likewise and rapidly reduces the size of the gland. They competitively block the binding of testosterone to its receptors and decrease libido within 3 days. One example is cyproterone acetate, furthermore delmadinone acetate. Some preparations are not licensed for use in animals. These medicaments caused a reduction in canine prostate gland size by 28% within two weeks [82], and the clinical symptoms improved earlier. The duration of effectiveness is approximately 6 months when an average dose of 3 mg/kg is chosen. Side effects in male dogs are a latent diabetes mellitus and diseases of the mammary gland (tumors, hyperplasia, cysts, and galactorrhea).
For breeding dogs, medicaments not decreasing the libido are desirable, enabling examination of the semen quality while the dogs are still under treatment. for example osaterone acetate is a gestagene with anti-androgenic effect. It decreases the uptake of DHT in the prostate gland and decreases the activity of the 5α-reductase. Osaterone acetate furthermore suppresses the nuclear DHT- and androgen-receptor expression in the gland [86]. The size of the gland was significantly reduced to 62.6% within 7 days when a daily oral dose of 0.2–0.5 mg/kg was given [10]. A daily oral dose of 0.25 mg/kg for 7 days reduced the size to 64.3% within 14 days [84]; the testosterone concentration was significantly reduced for 3 months [10], then slowly increased, which is believed to point toward a low-grade anti-gonadotrophic effect [87]. The semen quality was low grade decreased during the therapy; the volume was decreased for 4 months. An increase in the percentage of morphological changings was observed 4 weeks after beginning of the therapy and during the following 1.5 months [10]. This medicament is recommendable for breeding dogs because of its rapid effect and the maintained libido. Within three months after beginning of the therapy, the sonographical appearance of the gland and the quality of the ejaculate are back to normal. Some side effects were observed: an increase in appetite for 1–3 weeks (3/15), lethargy (2/15), and low-grade loss of hair (1/15) [7].
This medicament is applicated orally; in case of vomiting, it is therefore not recommendable. In this case, injectable preparations are available for dogs.
In case of mild BPH, the 5α-Reductase-Inhibitor Finasteride is effective (for example Proscar® 5 mg Tabl. Merck, Vienna, A) [12]. Doses for dogs and duration of application are variable in the literature (Tab. 2) [42, 83]; however, the tablets should be given for 3–4 months. Since semen quality and libido are not changed by the medication, it is recommendable for breeding dogs [12, 83]. Finasteride is a teratogenic substance; nevertheless, fertility and resulting puppies are not concerned [85]. Side effects are not described.
For prolongation of an anti-androgenic therapy, long-lasting agonists of the gonadotropin-releasing hormone (GnRH) are suitable for dogs with BPH. Subcutaneous implants containing, for example, deslorelin (Suprelorin® 4.7 or 9.4 mg, Virbac, F) are licensed for male dogs and male ferrets. Many studies using different GnRH agonists and dosages are available, but difficult to compare [7]; however, deslorelin is the only licensed preparation. After resorption of a certain amount of GnRH, down-regulation of the GnRH receptors in the pituitary gland leads to a decrease in the secretion of the gonadotropins ”follicle stimulating hormone” (FSH) and ”luteinizing hormone” (LH), and consecutively to a decrease in the secretion of testicular testosterone by 90% and the spermatogenesis. The volume of the prostate gland decreases within 6 weeks by 50%, when a 4.7 mg implant is used [7, 51, 88], beginning after 37 days [51].
In dogs, the initial therapy leads to an increase in testosterone secretion; this flare-up can be suppressed by oral application of an antiandrogen. This is important in case of an acute enlargement of the gland with acute symptoms [7].
GnRH antagonists can be used for therapy of canine BPH, unfortunately, the second generation of these drugs caused anaphylaxis in some cases. Meanwhile better agonists, which are potent,long-acting, and without side-effect, are available; however, they are only licensed for use in humans. Acyline is a preparation of the third generation and was used in one study at a dose of 330 mg/kg s.c. in dogs, leading to a reversible decrease in FSH, LH, and testosterone over 9 days. When a long-acting GnRH-agonist was used in dogs, Acyline successfully prevented a flare-up. In addition, the prostate volume was decreased by 38% after 30 days, echogenicity and heterogeneity were decreased, and the resistency-index (Doppler sonography) was normal again.
[89]. Monthly injections are required, rendering this medicament for short-term and exceptional use only. Further investigations with long-acting preparations would be of interest. Other medicaments like estrogens, antiestrogens, aldosterone-receptor antagonists, alpha1A-adrenerge-receptor antagonists, phosphodiesterase (PDE)-5 inhibitor, vitamin D receptor agonists, and intraprostatic injection of botulinus toxin type A (BT-A) were investigated; however, they are now obsolete or proved to be ineffective [7].
In dogs, the clinical symptoms can be effectively treated; however, the course of the disease is recurrent. Castration will finally resolve the problem. In stud dogs, special medicaments not decreasing the libido are available and fertility prognosis is good.
Regular clinical and sonographical controls of the dogs are a good prophylaxis since only treatment or castration in time will prevent the disease. These controls are recommendable when the dog reached 40% of its estimated lifetime [18].
Cystic changes of the canine prostate gland (intraprostatic cysts) mostly develop in the aged gland, changed by BPH, because of accumulation of prostatic secretions in the dilated prostatic acini; furthermore because of obstruction, compression of intraprostatic channels, or accumulation of urine, when a connection between the cyst and the urethra exists [90, 91]. Paraprostatic cysts are dilated residua of the Wolff channels; they can be situated in the cranio-lateral, ventral or caudal region of the prostate, and reach a remarkable size. In some cases, they become mineralized [90, 92]. Secondary infections and abscesses can be complications. In one study the prevalence of prostatic cysts was 14% (12/85) and 42% out of these were secondary infected [90].
The symptoms are dependent on the disease. Many small intraprostatic cysts are asymptomatic in dogs until the enlarged gland causes problems. Intraprostatic cysts frequently occur in the course of BPH and prostatitis; later on, they can cause enlarged abdomen, abdominal pain, decreased well-being, and in case of rupture or secondary infection, an acute abdomen, and sepsis.
In dogs, diagnosis should be done by sonography or X-ray. Sonographically, cysts appear as hypo- or anechoic, round structures with a thin wall, sometimes sediment or internal cysts can be visualized [45]. (Figures 4 and 5). The cysts can be punctured and the contents examined cytologically and bacteriologically.
Sonography (B-mode) of a prostate gland with BPH and intraprostatic cysts.
A small cyst is visible (white crosses). Cysts up to 3 cm in diameter can regress with anti-androgen therapy. Cysts filled with urine have a higher recidive rate, also after puncture.
Sonography (B-mode) of a paraprostatic cyst.
On the left side, the urinary bladder is visible; the mucus membrane is irregular and thickened. To the right, a paraprostatic cyst is situated, filled with hypoechoic fluids. The dog showed mild symptoms of a BPH with bloody preputial discharge and stranguria.
As described in the chapter BPH.
Canine intraprostatic cysts up to 3 cm in diameter can be treated with a 5α-reductase-inhibitor (Finasteride) or with anti-androgens; mostly they regress within 2–3 weeks. When the treatment is ineffective or in case of larger cysts, they have to be punctured and the secretions aspirated or the cysts must be surgically removed. The puncture should be done with the aid of sonography and transcutaneously (Figure 6). The treatment mostly has to be repeated one to four times and only if these measures stay without success, the operation should be considered [93]. The ultrasound-guided percutaneous drainage with alcohol sclerotherapy is controversial, even though some reports are promising [94]. Recently, canine autologous platelet-rich plasma (PRP) obtained through separation of liquid and solid components from whole blood, it was instilled after removal of cystic fluid in dogs with BPH and prostatic cysts [95]. The PRP dose was half the fluid removed from the cyst. Sixty days later, the cysts were no longer detectable sonographically. The PRP is known to affect antibacterial, analgesic, and anti-inflammatory [96]. The surgical treatment and the treatment of abscesses will be discussed in the following chapter.
Transabdominal puncture of a prostate abscess.
The gland was visualized with a 7.5 MHz convex probe, the cyst was punctured with a 0.9×40 mm needle, connected to an extension and a three-way cock. The contents were sucked off with a sterile syringe and examined cytologically and bacteriologically.
As described in the chapter BPH
In dogs, inflammatory diseases can be acute or chronical; they are mostly complicated by infections that ascend via the urethra or spread via the blood circulation [39, 97]. Prostatitis therefore may occur in both castrated and intact dogs. In some cases, a BPH, squamous metaplasia or neoplasia is complicated by an infection. In one study, in 66.6% of male dogs with clinical BPH, bacteria were isolated in the sperm-rich phase of the ejaculate; out of these, 61.1% were positive for mycoplasms, and out of these, 54.5% were positive for
The acute prostatitis can cause severe symptoms like acute anuria or obstipation. A frequent symptom in dogs is purulent-bloody preputial discharge. Fever, inappetence, vomiting, and diarrhea are possible. In case of an abscess, palpation of the gland is highly painful and fluctuation is typical; rupture will cause septic shock.
The chronical prostatitis usually starts with symptoms of the BPH, and then the course is recurrent, causing loss of weight and shaggy hair. Superinfections frequently occur.
The diagnosis should be done by clinical examination of the dog, sonography, and examination of urine and semen inclusive bacteriological examination. In addition, prostate secretions and the contents of cysts can be examined cytologically [19]. Rectal palpation will be painful. The gland can be asymmetric; the consistency will be elastic in case of acute inflammation, in case of chronical inflammation increased and sometimes hard, the surface can be uneven.
In dogs, hematuria and bloody preputial discharge frequently occur, and pyuria or purulent discharge may occur in case of prostate gland abscess. Bacteriological examination is mostly positive [41].
Blood picture: in case of acute prostatitis and abscesses, leucocytosis and neutrophilia are frequent, in chronical prostatitis, these findings may be lacking. An increased concentration of the enzyme canine-prostate-specific esterase (CPSE) may indicate a prostatic disease; however, differentiation between BPH, prostatitis, and neoplasia is not possible in dogs. Furthermore, the literature provides variable cut-off values [48, 75, 77] and the secretion of the CPSE is age-dependent in dogs. The measured values, therefore, have to be carefully interpreted; the diagnosis must include other findings.
Semen collection in case of acute prostatitis will not be possible but may be helpful in case of the chronical prostatitis. The semen quality initially shows the same abnormalities as in BPH and will decrease in case of infection. Admixture of erythrocytes is a frequent finding, furthermore decreased motility and an increase in morphological abnormalities [19, 39, 40]. The bacteriological examination of the semen or prostatic secretions is mostly positive [7, 9, 39]; additional cytological examination of the prostatic secretions is useful, in case of acute prostatitis and abscesses, granulocytes, blood cells, and bacteria are frequently found, whereas prostate cells appear normal [42, 99].
In dogs, the cytological findings correlate well with the patho-histological findings [39]; however, not with the bacteriological findings [100]. Collection of prostatic secretions is not sterile because of the physiological mixed flora in the urethra [101]; therefore, the quantitative bacteriological findings have to be considered as well.
The transcutaneous, sonographically guided fine-needle-aspiration (FNA) of the prostate tissue and puncture of fluid-filled cysts are important for differentiation between canine BPH and chronical prostatitis or neoplasia [39, 41, 44, 102] (Figure 6). The collected material should be examined cytologically and bacteriologically. Up to 70% of prostatitis cases were correctly diagnosed by use of FNA [102]. Complications rarely occur; in some cases, low-grade bleeding and inflammation were observed, especially in case of inflammatory changings [93]. Even though at the time of puncture or FNA it is not known, whether the obtained material is infectious or not, the procedure is safe for the patient, when performed in a sterile manner. The dog should receive nonsteroidal anti-inflammatory drugs (NSAID) for 3 days after the puncture and should be treated as soon as possible with suitable antibiotics according to the resistance test. In rare cases, spreading of tumor cells is possible [103].
B-mode-Sonography: in dogs, enlargement, asymmetry, and heterogeneity are prevailing symptoms. In case of acute prostatitis and abscesses, hypoechogenic sites can be found (Figure 7); in chronical prostatitis, hyperechoic sites are frequent, and in case of neoplasia also mineralization (Figure 8) [45, 63, 104].
Sonography of a prostate gland with acute prostatitis.
Prostate gland of a 12-year-old dog with fever, apathia, urine loss, obstipation, and a painful abdomen. The prostate gland was painful upon digital-rectal palpation. The gland was high-grade enlarged and the structure was inhomogenous. An intraprostatic cyst, 1,5x2 cm in size, was visible. The urine was examined bacteriologically and
Sonography of a chronical prostatitis.
The gland was high-grade enlarged and the structure was inhomogenous, mainly most areas hyperechoic. Very small cysts were visible. The dog showed chronic recurrent bloody preputial discharge, dyschezia, and obstipation. The semen was examined bacteriologically and ++
Unfortunately, it is not possible to differentiate between chronically inflammatory and tumorous changings, not with B-mode and Doppler sonography; in these cases, an FNA or biopsy is obligatory in dogs [8, 44, 73]. With grey-scale or pulse-wave Doppler-sonography, it was not even possible to differentiate between inflammatory and normal canine tissue [105]. Similarly, other imaging methods like CT or MRI cannot provide a secure diagnosis; however, in case of canine prostatitis, the CT findings correlated well with the CT outcome [68]. When using CT, the age of the dog must be considered since the normal CT findings change in the aging dog. The prostate growth shows three phases [106]: during the first phase (1–5 years), the gland reaches normal morphology; in the second phase (6–10 years), first hyperplastic changings occur; and in the third phase (≥11 years), senile involution is typical. These changings can be observed in the CT pictures as well [67].
As described in the chapter BPH, the echostructure analysis revealed typical findings in case of prostatitis; homogeneity was significantly decreased in comparison to BPH [62]. Further investigations are necessary to prove these first results.
BPH and neoplasia of the prostate gland have to be considered.
In acute canine prostatitis, typically, high-grade disturbance of the general conditions occurs; furthermore, acute urination and defecation problems require emergency measures. The rapid reduction of the prostate gland size is important, in addition to effective treatment of the infection. Intravenous infusions of physiological solutions are necessary for treatment of circulatory disturbances. Drugs against pain and inflammation such as NSAID and/or morphine derivates should be given (for example Carprofen 4 mg/kg SID i.v. or Buprenorphin 0.01–0.02 mg/kg every 6–8 h i. v.). In case of vomiting, metoclopramide injections are useful (0.5–1 mg/kg, BID-TID, s. c., i. m., i. v.) or maropitant (1 mg/kg SID s. c., i. v.). Dogs should be In-patient while treated until improvement.
Antibiotics have to be chosen according to a resistance test and according to the ability to penetrate the diseased tissue. In acute cases, the blood-prostate barrier is ruptured; therefore, each broad-spectrum antibiotic can be applied when effective according to the resistance test [97, 107]. Meanwhile, it is important to not only examine for bacteria but also for mycoplasms (M.) and ureaplasma (U.) inclusive specification and quantification;
In chronical canine prostatitis, the blood-prostate barrier is intact; therefore, antibiotics must be chosen according to the resistance test and the ability to penetrate the tissue. The latter is possible by using weak alkaline medicaments with a high pKa-value (acid-dissociations constant), good fat solubility, and weak protein binding [97]. In these cases, fluoroquinolones and erythromycins are good options as well, furthermore clindamycin and chloramphenicol.
In both acute and chronical prostatitis, the duration of treatment is important; in chronical cases, 4–6 weeks and up to 8–12 weeks are recommendable in dogs [19, 107]. One week after the end of the antibiotic treatment, another bacteriological examination should be done [19].
In dogs, prostate abscesses can be punctured and emptied; for this measure, a mild sedation is required. The needle should be carefully placed under sonographical control and samples for cytological and bacteriological examination obtained (Figure 6); sometimes one to four repetitions are required and in some cases, operative removal of the abscess is necessary [93]. Operative treatment is possible by marsupialization, a Penrose drain, or partial prostatectomy [109, 110, 111, 112]; a further method with low recidivism rate is the operative drainage of the abscess cavity and consecutive filling with omentum (omentalization)[112]. The prostate has to be pulled out of the abdomen; the contents of the abscess are sucked off (Figure 9a and b), then the opening is enlarged and the cavity flushed. Another opening is cut into the opposite side of the gland (Figure 9c) and the omentum is pulled into and through the cavity. The omentum is fixed with a suture on the opposite side of the gland. Additional application of antiandrogens and antibiotics according to a resistance test are necessary measures.
Omentalisation of a paraprostatic cyst (a); The huge paraprostatic cyst was situated behind the urinary bladder (to the right, black arrow). The wall was high grade thickened. (b) The urinary bladder was emptied and the prostate cyst was pulled out of the abdomen (c) After puncture of the cyst the contents were sucked off, then a large piece of the wall was removed on both sides of the cyst by using a sealing device (LigaSure™, Medtronic, Vienna, A). The omentum was pulled into the cavity and fixed on both sides of the cyst by using resorbable material.
The clinical symptoms can be effectively treated in both acute and chronical cases; however, the course of the disease is recurrent. Fertility prognosis is good when treated in time, with well-chosen medicaments, and over a sufficient period.
Regular clinical and sonographical examinations, starting when the dog reached 40% of the estimated life expectation, are recommendable [18].
Squamous metaplasia develops because of an endocrine active testicular tumor, secreting androgens and causing hyperestrogenemia, but in addition because of exogenous estrogens [113]. The metaplasia causes a morphological change in the gland, sonographically resembling an inflammation; sometimes cysts occur.
The disease is a side effect of hyperestrogenemia since this problem causes the clinically relevant changes in the blood picture and causes organ damages. Typical symptoms are alopecia, hyperpigmentation of the abdomen and inguinal region, gynecomastia, and in severe cases anemia.
The diagnosis can be made with FNA; however, rapid diagnosis and treatment of the hyperestrogenemia are more important. Mostly castration will solve the problem. However, it is important to know that the hyperestrogenemia can persist for months after the removal of the testicular tumor. Recurrence of the problem after castration may point toward metastasis.
When the dog is castrated, the estrogen concentration slowly decreases over weeks and months. During this time, infections frequently occur. Dependent on the degree of anemia and organ damage, a careful prognosis is appropriate. In case of low-grade changings and correct treatment, the prognosis is good.
Prostate gland tumors are seldom in dogs (<1%, [16, 114] and mostly malign adenocarcinomas or transitional cell carcinomas and seldom lymphomas [41]. The cells of origin sometimes are not identified [15, 115]. They are more frequently diagnosed in castrated than in intact dogs, the growth is not androgen-dependent [[14, 15, 116]. Other diseases of the prostate gland are not predisposing [19]. It is not known, whether the age at castration plays a role [16]. However, the age itself is an important factor, since the disease mainly is diagnosed in dogs aged > 8 years [51, 117, 118, 119]. Medium to large size breeds are more frequently concerned than smaller or toy breeds [14, 114]. A breed disposition is not proven; however, a higher risk/odds ratio was found for Shetland Sheepdog, Scottish Terrier, Bouvier des Flandres, Doberman, and mongrels [9, 14, 120].
Recent studies investigated changes in the prostate gland during cancer development at the molecular level. A lack of androgen receptor and the overexpression of P-glycoprotein (P-gp) was described, indicating that androgens do not play an important role in pathogenesis [116]. P-glycoprotein regulates the influx and efflux of testosterone in prostatic cells. New findings suggest NF-kb dysregulation as a probable factor contributing to oncogenesis; chronic inflammations may trigger the change in precancerous cells causing DNA and epigenetic damage [121]. NF-kb is an inducible cytoplasmic transcription factor, able to activate genes for inflammatory cytokines, adhesion molecules, enzymes related to inflammation (such as cyclooxygenase-2), telomerase, antiapoptotic proteins, and cell cycle-regulatory genes [121].
The growth is most aggressive with an invasion of surrounding tissues and high metastatic potential. The incidence of metastases varies between 16% and 80%, dependent on age [119, 122]; the sites of metastasis are primary the lung, then regional lymph nodes, liver, urethra, spleen, colon and rectum, urinary bladder, bones, heart, kidney, and adrenal gland, but also the skin [123]. Metastases are mostly already present at the time of diagnosis of the prostate gland tumor [19].
The symptoms vary independently on castration status; in some dogs, gastrointestinal symptoms are predominant (defecation problems, tenesmus), in others, symptoms of the urogenital tract occur first (stranguria, hematuria, incontinence, dysuria, pollakisuria, and polydipsia). Enlargement of the gland was observed in only 45% of cases [119]. In some dogs, lameness, loss of weight, and abdominal pain become obvious, especially, when metastases occur [9, 114].
Since the symptoms are unspecific, a prostate gland tumor must be considered in aged dogs with severe symptoms of a disease of the urogenital tract and gastrointestinal symptoms [16].
Prostate gland tumors are frequently diagnosed too late when the aggressive invasive growth already caused massive tissue damage and metastases. Accompanying inflammation and secondary infections of the urogenital tract complicate the diagnosis. However, early detection is an important factor for survival.
Digital rectal palpation may reveal an uneven surface, immobility, asymmetry, and/or painfulness. A blood picture can show neutrophilia, leucocytosis and in 70% an increase in alkaline phosphatase concentration. Pyuria and hematuria are possible; in the sediment, tumor cells can be detected [119].
However, cytological examination of urine or prostate secretion sediment is unreliable, even when the cytobrush method was used. For the final diagnosis, a biopsy and histological examination of the tissue are obligatory. Transcutaneous FNA has a sensitivity of 80% [119], which can be increased to 89% by punch-biopsy or excisional biopsy [102, 103, 124]. For punch-biopsy or excisional biopsy, total anesthesia is required. The gland has to be pulled forward to be able to perform the biopsy on the ventrolateral surface. The wound is closed with single sutures, including the capsule and parenchyma [125]. Histologically, a prostatic adenocarcinoma can be differentiated from a prostatic carcinoma, urothelial, and tumors of mixed morphology [124, 126]. A possible side effect is the spread of tumor cells [103].
Sonography is not useful to differentiate between inflammation and neoplasia; however, can be helpful [45, 63]. With B-mode, the gland appears inhomogeneous, with hyperechoic areas; mineralizations are frequent and the borders in > 80% of cases appear irregular and diffuse against the rectum, and sometimes even rupture. In many cases, the regional lymph nodes are changed [119]. (Figure 10)
Sonography of a carcinoma of the prostate gland (B-mode).
The male dog showed chronical prostatitis, loss of weight, and a matt coat. The prostate gland was only low-grade enlarged, but high-grade inhomogeneous, with mineralizations. The margin was not well defined and could not be separated optically from the wall of the rectum. Small intraprostatic cysts were visible. FNA of the gland was performed and revealed the diagnosis of prostate carcinoma.
Some imaging methods were improved. With contrast-enhanced-Doppler sonography it is possible to visualize the perfusion in the normal prostate tissue and to compare it with prostate neoplasia; in case of adenocarcinoma, the perfusion was significantly higher [81]. Elastography was used in one Labrador dog with prostatic adenocarcinoma, and the histological result of the FNA correlated well with the findings of the elastography [121]. A new experimental method is a combination of simultaneous magnet-resonance spectroscopy (MRS), positron-emission-tomography (PET), and multiparametric magnet-resonance (mpMR). In one study, the results were compared with findings from transrectal sonography and prostate biopsy. In 3/3 dogs, tumor growth was diagnosed by using the combined method; the diagnosis was verified by biopsy [71].
An X-ray of thorax and abdomen should be done to diagnose metastases in the lymph nodes, pelvic bones, and the lung [11, 41].
Recent studies focus on the detection and development of biomarkers for canine prostate cancer [126, 127]. Markers are not easy to find in case of canine prostate cancer since the tumor growth is aggressive and the pattern variable, the basal cell layer is discontinuous and markers are frequently absent. A combination of markers might increase the diagnostic accuracy [127]. For a precise immunohistochemical analysis, different markers are necessary to differentiate between urethral, glandular, or ductal origin of the tumor, which is possible in human medicine but not sufficiently investigated in the dog. In dogs, the prostate cancer most probably originates mainly from collecting ducts [128]. In one study, qPCR revealed increased expression of PSMA in all cancer tissues [128].
In dogs, both urothelial carcinoma of the lower urinary tract and prostate cancer may occur. In both cancer types,
To differentiate between urothelial and prostate carcinoma, a combination of markers will be necessary. In a recent study [131], the chemokine CCL17 was found to contribute to regulatory T cell (Treg) recruitment in prostate tumors. In dogs with prostate cancer, tumor-infiltrating Tregs were found to be associated with bad prognosis [132]. In urine samples of dogs with urothelial cancer, increased concentrations of CCL17 were found in comparison to healthy dogs. The
In one study, RNA-Sequencing of canine normal prostate gland tissue and malignant tissues was performed to find differentially expressed genes (DEGs) and deregulated pathways. The detected DEGs were grouped into the superior pathways (1) inflammatory response and cytokines; (2) regulation of the immune system and cell death; (3) cell surface and PI3K signaling; (4) cell cycle; and (5) phagosome and autophagy. Meanwhile, some genes were listed in relevant databases and might improve diagnosis and therapy in future.
Furthermore, canine prostate cancer cell lines have been developed making investigation of molecular mechanisms easier [134]; one cell line expressing red-fluorescence proteins was developed to improve in-vivo imaging [135].
BPH, chronical prostatitis, or other tumor diseases must be considered, especially in case of weight loss.
Conservative therapy comprises chemotherapy and palliative measures and shall improve the median survival time (MST) and well-being. Surgical treatment is possible; partial and total prostatectomy followed by chemo- and radiotherapy, photodynamic therapy and COX inhibitors [15] are possible methods. Castration is not useful and should not be recommended [19, 119].
Prostate surgery is mostly recommended in case of intracapsular growth and early-stage cancer. For total prostatectomy, the prostate-inclusive prostatic urethra has to be removed; thereafter, the urethra is reconstructed. Subtotal intracapsular prostatectomy proved to prolongue the MST more than 5fold in comparison to total prostatectomy (112 ± 63.3 days vs 19.9 ± 10.67 days [136]. Most frequent postoperative complication is a permanent incontinence, occurring in 33–100% of cases; however, less frequent after subtotal intracapsular prostatectomy [136, 138]. In one retrospective study [139], the postoperative survival time (time between operation and death) was 231 days (median; range: 24–1255 days). In the evaluated studies, ureter-urethral anastomoses (14), cysto-urethral anastomoses (9), anastomoses between ureter and colon (1), and anastomoses between urinary bladder neck and pelvic part of the urethra were described (1). The dogs in addition received mitoxantrone, NSAID, metronomic thalidomide, cyclophosphamide, piroxicam, carboplatin, and/or deracoxib. In 8/23 dogs, postoperative incontinence occurred. Further complications were dehiscence of sutures, uroabdomen, and prepubic herniation. In 3/23 dogs a recidive occurred, in 4/23 metastases were diagnosed [139].
Another study compared the outcome of medical therapy (n=12) and surgery in dogs with adenocarcinoma of the prostate gland [140]. The surgery comprised total prostatectomy (TP, n=20)) and prostatocystectomy (TPC, n=9). In the surgical group, the overall MST was longer than in the medical treatment group (337 vs. 90.5 days). Within the surgical group, the postoperative MST was longer in the TP group (510 vs. 83 days). In case of aggressive prostate cancer, TPC is preferred, therefore more severe complications occur, explaining the shorter MST.
In recent years, the surgery was improved by use of Light-Amplification by Stimulated-Emission-of-Radiation (laser). Meanwhile, the method is used for prostatectomy. The laser (Diode, Nd:YAG or CO2) must be adapted to the predominating tissue, i.e. the vascularization and the pigment since the absorption spectrum can be influenced by melanin, hemoglobin, and water. For prostatectomy, the CO2 laser in combination with electrocautery was proven advantageous [141].
Immunotherapy is under intense investigation in human medicine and recently, a promising study in dogs with naturally occurring prostate cancer was published [132]. In this study, the presence and molecular mechanism of targeting regulatory T-cells (Tregs) were studied in canine cancer cells and an anti-Treg treatment (anti-human CCR4, mogamulizumab) in combination with Piroxicam tested in dogs with prostate cancer. The tumor response was evaluated according to canine response evaluation criteria [142]. The presence of tumor-infiltrating CCR4 Tregs was found to be associated with bad prognosis. The anti-CCR4 compound reduced circulating CD4+Foxp3+ Tregs and CCR4+ Tregs, furthermore, the number of local CCR4 cells was reduced. The combined treatment with piroxicam better reduced the tumor size than piroxicam alone. The median progression-free survival time (PFS) was 204 (21–573) days and 57 (6–210) days in mogamulizumab/piroxicam dogs and piroxicam dogs, respectively; the respective OS time was 312 (86–1000) days and 99 (6–468) days. Observed clinical side effects were grade 1 or 2 (vomiting, anorexia, pancreatitis, urticaria, rash, and infusion reaction).
Modern studies investigate molecular targets like tight junction proteins. A recent in vitro approach used prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) cell lines to investigate whether it is possible to destroy tumor cells by gold-nanoparticle-mediated laser perforation (GNOME-LP [143]), a noninvasive thermotherapy. The gold-nanoparticles (AuNPs) were conjugated to
In human medicine,
Another interesting method is the prostate artery chemoembolization, causing necrosis of prostate gland and tumor tissue and a decrease in prostate volume of approximately 70% in one study [146]. The method is promising; however, since all dogs died because of metastases within 9 months, improvement of early diagnosis of the disease is most important.
Diseases of the prostate gland are frequent disorders of the aging dogs. The symptoms sometimes are unspecific; however, in case of urination and defecation problems in older male dogs, the enlarged prostate gland must be considered. The andrological examination must include the whole urogenital tract. The Benign Prostate Gland Hyperplasia (BPH) develops slowly and mild symptoms like bloody preputial discharge are typical at the beginning. Using routine diagnostic pathways, starting with a thorough case history followed by clinical examination including digital-rectal palpation and B-mode sonography, the correct diagnosis is quickly made in most cases. Measurement of the CPSE serum concentration can be done; however, the result must be carefully interpreted, considering the age of the dog. When the well-being of the dog is disturbed or sonography of the prostate gland reveals signs of a chronical inflammation, further examinations are necessary. Semen collection with cytological and bacteriological examination of the sperm-rich fraction or prostatic secretion is one possibility. If this is not possible, transcutaneous puncture of cysts can be performed, eventually followed by FNA or biopsy of the diseased tissue. All samples should be examined cytologically and bacteriologically; cytological findings well correlate with FNA findings, and the bacteriological examination should always be combined with a resistance test, since antibiotics in chronical cases, have to be applied for weeks. Prostate gland tumors can only be diagnosed by FNA or biopsy; the search for reliable biological markers and new imaging methods is ongoing. New therapeutical methods such as immunotherapy combined with NSAIDs, targeted noninvasive thermotherapy,
The author declares no conflict of interest
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TME is a complex network composed of extracellular matrix (ECM), stromal cells, and immune/inflammatory cells that drive cancer cells fate from invasion to intravasation and metastasis. The stromal-inflammatory interface represents a dynamic space, in which exchange of numerous molecular information is associated with the transition into tumorigenic microenvironment. Recruitment, activation, and reprogramming of stromal and immune/inflammatory cells in the extracellular space are the consequences of a reciprocal interaction between TME and cancer cells. Recent data suggest that cancer development is influenced by TME and controlled by the host’s immune system, underlying the importance of TME components and immune biomarkers in the determination of prognosis and response to therapy. The immune classification has prognostic value and may be a useful supplement to the histopathological, molecular, and TNM classifications. Nevertheless, the complexity of quantitative immunohistochemistry and the variable assay protocols, stromal and immune cell types analyzed underscore the need to harmonize the quantified methods. It is therefore important to incorporate TME and immune scoring in determinations of cancer prognosis and to make sure they become a routine part of the histopathological diagnostic and prognostic assessment of patients.",book:{id:"6297",slug:"histopathology-an-update",title:"Histopathology",fullTitle:"Histopathology - An Update"},signatures:"Kinan Drak Alsibai and Didier Meseure",authors:[{id:"215311",title:"Dr.",name:"Kinan",middleName:null,surname:"Drak Alsibai",slug:"kinan-drak-alsibai",fullName:"Kinan Drak Alsibai"},{id:"215546",title:"Dr.",name:"Didier",middleName:null,surname:"Meseure",slug:"didier-meseure",fullName:"Didier Meseure"}]},{id:"41353",doi:"10.5772/50659",title:"Morphology of the Intestinal Barrier in Different Physiological and Pathological Conditions",slug:"morphology-of-the-intestinal-barrier-in-different-physiological-and-pathological-conditions",totalDownloads:4236,totalCrossrefCites:5,totalDimensionsCites:13,abstract:null,book:{id:"2619",slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Jesmine Khan and Mohammed Nasimul Islam",authors:[{id:"140755",title:"Dr.",name:"Jesmine",middleName:null,surname:"Khan",slug:"jesmine-khan",fullName:"Jesmine Khan"},{id:"163192",title:"Prof.",name:"Mohammed",middleName:null,surname:"Islam",slug:"mohammed-islam",fullName:"Mohammed Islam"}]},{id:"41359",doi:"10.5772/52376",title:"Nocardiosis: Clinical and Pathological Aspects",slug:"nocardiosis-clinical-and-pathological-aspects",totalDownloads:4749,totalCrossrefCites:2,totalDimensionsCites:10,abstract:null,book:{id:"2619",slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Sharmila P. Patil, Nitin J. Nadkarni and Nidhi R. Sharma",authors:[{id:"139808",title:"Dr.",name:"Sharmila",middleName:null,surname:"Patil",slug:"sharmila-patil",fullName:"Sharmila Patil"},{id:"141615",title:"Dr.",name:"Nitin",middleName:null,surname:"Nadkarni",slug:"nitin-nadkarni",fullName:"Nitin Nadkarni"}]},{id:"18771",doi:"10.5772/20385",title:"Electron Microscopy of Liver Biopsies",slug:"electron-microscopy-of-liver-biopsies",totalDownloads:8263,totalCrossrefCites:3,totalDimensionsCites:10,abstract:null,book:{id:"287",slug:"liver-biopsy",title:"Liver Biopsy",fullTitle:"Liver Biopsy"},signatures:"Theodore C. Iancu and Irena Manov",authors:[{id:"38689",title:"Dr.",name:"Theodore",middleName:null,surname:"Iancu",slug:"theodore-iancu",fullName:"Theodore Iancu"},{id:"38699",title:"Dr.",name:"Irena",middleName:null,surname:"Manov",slug:"irena-manov",fullName:"Irena Manov"}]}],mostDownloadedChaptersLast30Days:[{id:"59286",title:"Surgical Approaches to the Temporomandibular Joint",slug:"surgical-approaches-to-the-temporomandibular-joint",totalDownloads:6972,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The temporomandibular joint (TMJ) acts as a sliding hinge between mandible and temporal bone. Disorders of temporomandibular joint are intolerable for the patients in severe cases. Furthermore, surgical treatment of temporomandibular joint problems is a challenge for surgeons in some cases. In that order, it is critical for the surgeon to choose the best surgical approach in treating the temporomandibular joint diseases. There are several surgical approaches in the management of temporomandibular joint problems including some pros and cons. So, in this chapter, we aim to present a comprehensive review of surgical approaches to the temporomandibular joint.",book:{id:"6025",slug:"temporomandibular-joint-pathology-current-approaches-and-understanding",title:"Temporomandibular Joint Pathology",fullTitle:"Temporomandibular Joint Pathology - Current Approaches and Understanding"},signatures:"Mohammad Esmaeelinejad and Maryam Sohrabi",authors:[{id:"172188",title:"Dr.",name:"Mohammad",middleName:null,surname:"Esmaeelinejad",slug:"mohammad-esmaeelinejad",fullName:"Mohammad Esmaeelinejad"},{id:"240723",title:"Dr.",name:"Maryam",middleName:null,surname:"Sohrabi",slug:"maryam-sohrabi",fullName:"Maryam Sohrabi"}]},{id:"41355",title:"Ossifying Fibromas of the Craniofacial Skeleton",slug:"ossifying-fibromas-of-the-craniofacial-skeleton",totalDownloads:4831,totalCrossrefCites:5,totalDimensionsCites:6,abstract:null,book:{id:"2619",slug:"histopathology-reviews-and-recent-advances",title:"Histopathology",fullTitle:"Histopathology - Reviews and Recent Advances"},signatures:"Bruno Carvalho, Manuel Pontes, Helena Garcia, Paulo Linhares and Rui Vaz",authors:[{id:"140061",title:"Dr.",name:"Bruno",middleName:null,surname:"Carvalho",slug:"bruno-carvalho",fullName:"Bruno Carvalho"},{id:"142266",title:"Dr.",name:"Manuel",middleName:null,surname:"Pontes",slug:"manuel-pontes",fullName:"Manuel Pontes"},{id:"142267",title:"Dr.",name:"Paulo",middleName:null,surname:"Linhares",slug:"paulo-linhares",fullName:"Paulo Linhares"},{id:"142268",title:"Prof.",name:"Rui",middleName:null,surname:"Vaz",slug:"rui-vaz",fullName:"Rui Vaz"},{id:"142958",title:"Dr.",name:"Helena",middleName:null,surname:"Garcia",slug:"helena-garcia",fullName:"Helena Garcia"}]},{id:"58358",title:"Internal Derangements of the Temporomandibular Joint: Diagnosis and Management",slug:"internal-derangements-of-the-temporomandibular-joint-diagnosis-and-management",totalDownloads:3346,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Millions of individuals worldwide suffer from temporomandibular joint (TMJ) disorders and are characterized by pain and joint dysfunction. TMJ internal derangement (ID) is the most frequent type of temporomandibular disorders (TMDs). The ID of TMJ is defined as a joint dysfunction associated with an abnormal disc position. Identification and elimination of the causes of tissue breakdown of the TMJ that lead to ID are the key factors for successful treatment. The common causes for TMJ ID are trauma and parafunctional habits which lead to joint overload and degenerative changes in the articular structures, increased friction, and gradual disc displacement. Local and systemic inflammatory/degenerative arthropathies may also affect TMJ and cause ID. The aim of this chapter is to give comprehensive knowledge about the contemporary perspective of TMJ ID including diagnostic and therapeutic developments and innovations. Clinicians should establish the correct diagnosis and cause of the disease for appropriate management so that patients do not suffer from ineffective treatments. As an innovative development, TMJ replacements with alloplastic joint prosthesis and tissue-engineered structures hold promise for the future of management of TMJ ID.",book:{id:"6025",slug:"temporomandibular-joint-pathology-current-approaches-and-understanding",title:"Temporomandibular Joint Pathology",fullTitle:"Temporomandibular Joint Pathology - Current Approaches and Understanding"},signatures:"Ufuk Tatli and Vladimir Machon",authors:[{id:"203864",title:"Associate Prof.",name:"Ufuk",middleName:null,surname:"Tatli",slug:"ufuk-tatli",fullName:"Ufuk Tatli"},{id:"204401",title:"Dr.",name:"Vladimir",middleName:null,surname:"Machon",slug:"vladimir-machon",fullName:"Vladimir Machon"}]},{id:"61976",title:"Metabolic Alkalosis",slug:"metabolic-alkalosis",totalDownloads:1491,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Metabolic alkalosis is a disorder where the primary defect, an increase in plasma bicarbonate concentration, leads to an increase in systemic pH. Here we review the causes of metabolic alkalosis with an emphasis on the inherited causes, namely Gitelman syndrome and Bartter syndrome and syndromes which mimic them. We detail the importance of understanding the kidney pathophysiology and molecular genetics in order to distinguish these syndromes from acquired causes. In particular we discuss the tubular transport of salt in the thick ascending limb of the loop of Henle, the distal convoluted tubule and the collecting duct. The effects of salt wasting, namely an increase in the renin-angiotensin-aldosterone axis are discussed in order to explain the biochemical phenotypes and targeted treatment approaches to these conditions.",book:{id:"6790",slug:"fluid-and-electrolyte-disorders",title:"Fluid and Electrolyte Disorders",fullTitle:"Fluid and Electrolyte Disorders"},signatures:"Holly Mabillard and John A. 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SDGs emphasize that environmental sustainability should be strongly linked to socio-economic development, which should be decoupled from escalating resource use and environmental degradation for the purpose of reducing environmental stress, enhancing human welfare, and improving regional equity. Moreover, sustainable development seeks a balance between human development and decrease in ecological/environmental marginal benefits. Under the increasing stress of climate change, many environmental problems have emerged causing severe impacts at both global and local scales, driving ecosystem service reduction and biodiversity loss. Humanity’s relationship with resource exploitation and environment protection is a major global concern, as new threats to human and environmental security emerge in the Anthropocene. 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