Intraoral site involvement in 37 patients.
\r\n\tThis book will consist of chapters that are an elegant mix of reviews and current developments on the subject that will be useful both to an expert on the subject as well as a newcomer to this area of research.
",isbn:"978-1-83969-076-1",printIsbn:"978-1-83969-075-4",pdfIsbn:"978-1-83969-092-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"8a2fd9bbbbae283bf115881d9d5cc47a",bookSignature:"Dr. Ashim Kumar Dutta",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11857.jpg",keywords:"Frenkel Excitons, Wannier-Mott Excitons, Low Dimensional Solids, Molecular Crystals and Aggregates, Exciton Diffusion and Hopping, Exciton–Exciton Annihilation, Dynamics, Scaling Laws, Photoluminescence, Exciton Lifetime, Energy Harvesting, Semiconductors",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 19th 2022",dateEndSecondStepPublish:"May 17th 2022",dateEndThirdStepPublish:"July 16th 2022",dateEndFourthStepPublish:"October 4th 2022",dateEndFifthStepPublish:"December 3rd 2022",remainingDaysToSecondStep:"5 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ashim Kumar Dutta received his Ph.D. in physical chemistry from the Indian Association for the Cultivation of Science (IACS). 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Earlier, he had worked with Unilever as a senior researcher and product development manager in their Home and Personal Care Category, with United Phosphorus Limited and Indofil as their global head for agrochemical formulations. He has authored/co-authored 36 articles in international journals and 19 patents. He received his Ph.D in physical chemistry from Indian Association for the Cultivation of Science (IACS) – a premiere research institute in India in 1993. Dr. Dutta has worked on various international post-doctoral fellowships in Japan, Canada and USA. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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They have important characteristics; such as its ectothermic physiology, metabolism, and highly permeable skin, which makes them sensitive to disturbances in the ecosystem such as changes in water conditions, as well as the presence of pollutants and certain diseases [1, 2, 3]. This complex life cycle makes them susceptible to different routes of exposure to environmental pollutants, which is why they have been considered as bioindicators of environmental quality [4]. Currently, environmental pollution is considered one of the main factors in the worldwide decline of amphibians that has occurred since 1990 [5]. Some species of amphibians have all the characteristics of a bioindicator or biomonitor, other species can satisfy only some of the criteria and are less suitable as study animals [2, 6].
\nThe giant toad or cane toad (
Giant or cane toad (
In some of the previous research, different physiological responses have been used, from general to specific responses of pollutants from the study sites. These responses are called biomarkers, where all biochemical, physiological, histological, morphological, and behavioral measurements are quantifiable in tissue or biological fluids from different organisms, including amphibians, like the
Moreover, in Mexico, there are several types of environmental pollution scenarios that have not been assessed from the point of view of the effects to the biota living these sites. In addition to this, there are very little environmental regulations as to some types of pollutants, such as: persistent organic compounds (POPs), polycyclic aromatic hydrocarbons (PAHs), and heavy metals. One of the sites has a higher record environmental pollution is the region of the lower Coatzacoalcos River Basin (Veracruz); region highly impacted due to industrial activities and urbanization that have contributed to the deterioration of ecosystems since the 1960s. Currently, Coatzacoalcos is considered one of the most polluted regions in Mexico [22, 23], to such a degree that, in environmental matrices such as water, soil, air, or sediment, and even in fauna, the presence of POPs, volatile organic compounds (VOCs), dioxins, heavy metals, among others, has been detected [11, 24, 25, 26, 27]. Some of these pollutants have been associated with genotoxic or enzymatic effects in aquatic and terrestrial organisms at this site [10, 11, 28, 29]. In this context, the objective of this chapter is to present and compare the results of a monitoring of physiological responses (biomarkers) in
The lower basin of the Coatzacoalcos river is in the southeastern state of Veracruz, Mexico (18° 08′56” N; 94°24′41” W). It comprises 21 municipalities, which house petrochemical, industrial, urban complexes, and agricultural land areas. Pollution has been historic since oil exploration and refining works began at the beginning of the twentieth century up to industrialization, agricultural development, and urban growth at present, causing a rapid deterioration of the ecosystems found there.
\nThe sampling stations were established along the basin according to the degree of contamination found. Thus, they were grouped by two zones: industrial and rural. In May 2008, the first sampling of monitoring study was carried out, while the second was carried out in February 2016 (Figure 2).
\nZones of sampling in low basin of Coatzacoalcos (source: Google Earth, 2016).
The industrial zone (I) was formed by the following sampling stations (red oval, Figure 2):
Ejido Cangrejera: site adjacent to the petrochemical complexes of Pajaritos and Cangrejera, where various derivatives of chlorine and ethylene compounds are produced. In addition, the presence of POPs in both environmental and biological matrices has already been evidenced in this area, as well as the effects that these could be causing in terrestrial organisms [24, 28, 29].
Estero del Pantano: site located on the banks of the Calzadas River. According to [11] the river receives discharges of sewage and industrial waters. Also, the presence of POPs and lead (Pb) has been demonstrated, as well as the effects of these compounds on terrestrial and aquatic organisms [10, 11, 30].
While the rural area (R) (yellow oval, Figure 2) was formed by:
Ejido Limonta: Located upstream of the Coatzacoalcos river, in the municipality of Hidalgotitlán. It presents scarce urbanization and ecosystems still well preserved. At present, concentrations of pollutants have not been reported in this sampling station.
San Carlos: Located next to the Uxpana river, upstream and that ends at the Coatzacoalcos river. It has well-preserved ecosystems. Like the previous one, no contaminant concentrations have been reported in this site.
The sampling stations of the rural area selected are characterized by semi-preserved ecosystems and minor impact by agricultural production, being susceptible areas where organophosphorus, organochlorine, or carbamate pesticides can be used to control pests or vectors.
\nAs a reference, giant toads (seven organisms) kept in the laboratory for 1 year under conditions of feeding, humidity, and controlled temperature were selected, collected in a site outside the study area (Huasteca Potosina, San Luis Potosí) and free of exposure to pollutants.
\nAdult male giant toads were collected per site by night transects and hand capture. In the first sampling (May 2008), 40 toads were collected, while in the second sampling (February, 2016), 30 toads were collected. The organisms were transported in containers to the laboratory (Facultad de Química-Universidad Veracruzana-Campus Coatzacoalcos). The body weight and snout-venth length (SVL) were taken. Subsequently, a blood sample (3–5 mL) was taken with heparinized syringes (following the guidelines established for amphibians and reptiles [31]). An aliquot of whole blood was stored in liquid nitrogen (−186°C) for enzymatic analysis. While with the rest the hematological parameters were analyzed. The toads were released in their respective habitat. The toads were collected under a scientific collection permit (SGPA/DGVS/09731/15) issued by the Secretaría de Medio Ambiente y Recursos Naturales (SEMARNAT).
\nThe inhibition of the activity of the enzyme δ-ALAD is a biomarker that has shown in several studies a response to a specific contaminant. This enzyme is very sensitive to the effects of increased blood lead, even at very low levels [32]. In the biosynthesis of the heme group, the prosthetic group of hemoglobin (Hb) is selectively damaged by the binding of lead, thus affecting important steps of biosynthesis, inhibiting the activity of δ-ALAD (necessary for the synthesis of the heme group), and affecting the synthesis of protoporphyrin IX and hemoglobin [33, 34].
\nThe determination of δ-ALAD was based on the method of [35] following modifications [11]. The whole blood samples (0.05 mL) were diluted with deionized water (1:35). Then 1 mL of 10 mM aminolevulinic acid (in phosphate buffer pH 6.4) was added. The samples were incubated at 38°C for 60 min in a water bath in complete darkness. The reaction was stopped by placing 1 mL of trichloroacetic acid (10%), then the samples were centrifuged for 10 min at 2000 rpm (Thermo Scientific® Sorvall Legend X1R). The supernatant was mixed with 1 mL of the Erich’s solution. After 10 min, the absorbance was measured at 555 nm in a UV–Visible spectrophotometer (Thermo Scientific® Genesys 10S). Units of enzymatic activity were expressed as micromole per min per liter of red blood cells (RBC), which were calculated using the following formula (Eq. 1):
\nwhere Abs = absorbance of the sample,
The chemical and morphological parameters of the blood can provide a wide range of biomarkers; its use has increased because the sampling can be very fast and non-destructive [36]. The hematological parameters can provide evidence of pathology including anemia, dehydration, infectious processes, parasitism, or poisoning [37]. These parameters in turn may be related to pollution and its effects [38]. The volume of the cell pack or hematocrit (HT) is the percentage of the total volume of blood composed of red blood cells. The mean corpuscular hemoglobin concentration (MCHC) is the range of the weight of hemoglobin by the volume of the erythrocyte. An iron deficiency, increased immature erythrocytes (reticulocytosis) and methemoglobin can result in a decrease in MCHC values [32]. Some toxic compounds can alter the functioning of the hematological system through interference with cellular production in the bone marrow or in the synthesis of the heme group, by direct cytotoxicity to the cells, or by injuries in other tissues resulting in a loss of blood cells [32, 39].
\nTherefore, the hemoglobin (Hb), hematocrit (HT), and the mean corpuscular hemoglobin concentration (MCHC) were determined. The hemoglobin content (g/dL) was measured using the kit HemoCue Hb 201+ (microcuvettes and HemoCueHb 201+ Analyzer). The determination was made following the protocol of the commercial distributor [40]. The hematocrit was determined with the globular sedimentation method with the aid of the hematocrit chart (Critocaps™ tube reader). The MCHC was calculated integrating the two previous parameters following equation.
\nCondition indices are potentially attractive biomarkers because they are simple to implement and provide information on the use of energy as well as the general health status of the organism [41]. The morphometric index most used is the condition factor (CF) expressed as the weight (g)/length (cm). Pollutants can produce rapid and marked changes in condition indices.
\nTo calculate the CF, the snout-vent length (SVL) of the toads was taken with a vernier caliper (mm) and its body weight (BW) (g) with an electronic scale. Subsequently, these two parameters were integrated and used the following formula (Eq. (3)) to calculate the CF (%).
\nThe statistical analysis was carried out with the GrapPhad Prism 6.0 software (for Windows, La Jolla California USA, www.graphpad.com). The results are reported in media ± standard error. A comparison analysis of means (Mann-Whitney test) was carried out to evaluate the differences between the biomarkers per years, with a level of significance of 1 and 5%. To evaluate the difference in δ-ALAD between years, zones, and the laboratory, the Kruskall-Wallis test was used. A correlation between δ-ALAD and hematologic parameters (Log-transformed) was realized with Spearman’s test.
\nThe results of the δ-ALAD activity in blood of
Comparison of biological responses (biomarkers) in blood of giant toad (
The δ-ALAD activity has been shown to be a specific biomarker for evidence of lead exposure in organisms such as birds, amphibians, and mammals, both in the field and in the laboratory [42, 43, 44]. Our results show that, in 2008, toads from the industrial zone showed an inhibition of the δ-ALAD enzyme compared to those from the rural zone, which can be consistent and expected if this area is taken as a reference. This inhibition can be attributed to concentrations of lead found in the blood of giant toads, where residents of the industrial zone contained higher concentrations of this metal [11]. However, for 2016, the activity of δ-ALAD was similar for both areas. Refs. [33, 43] demonstrated in laboratory studies that exposure to lead in adult toads (
On the other hand, the δ-ALAD activity in the laboratory toads was greater for those of Coatzacoalcos; this would also confirm an enzymatic inhibition in the organisms of this region, increasing in recent years. Finally, it could be said that the δ-ALAD activity could reflect a chronic exposure to lead, because the erythrocytes that carry out the transport of hemoglobin have a half-life of between 700 and 1400 days in
The concentrations of hemoglobin and the percentage of hematocrit are presented in Figure 3. No statistical differences were found per year between zones (MW-U, p > 0.05). The levels of both parameters were similar in the toads resident in the rural area in 2008 (Hb = 9.05 ± 0.4 g/dL, HT = 34.6 ± 1.9%) and 2016 (Hb = 8.3 ± 0.4 g/dL, HT = 37.4 ± 1.6%) as well as those of the industrial zone in both years (Hb = 7.6 ± 0.3, HT = 32.3 ± 1.4; Hb = 7.9 ± 0.7 g/dL, HT = 30.7 ± 2.2%, respectively) (Figure 3B and C). However, when comparing by area in each year, a statistically significant decrease in the hemoglobin concentration of
Very few studies, in relation to pollutants and hematological parameters, have been carried out with amphibians. [51] used these parameters to evaluate the effects of agroecosystems on the health of amphibians; however, no statistically significant differences were found between the reference site and the agroecosystems. The results obtained in our study are contrary to those obtained in [52] where they showed a decrease in hematological parameters according to the presence of lead in tissues of the Egyptian toad
We consider that the hematological parameters of Coatzacoalcos toads are altered (increases or decreases) when comparing areas in both years. But not so, if they are compared per year between zones, because similar values are obtained in Hb and HT, only one alteration was found in the MCHC in the organisms of the rural area in 2016. The increase of some parameters, such as Hb, could be related to a response of organisms to a decrease in the transport of oxygen in the blood (hypoxia), derived from anemia (anemic hypoxia) [53]. Hypoxia in some vertebrate organisms (fish, amphibians) has been related to the natural and anthropogenic increase of ammonium, sulfides, or organic matter, as well as the presence of pollutants (organic or heavy metals—lead) and excess nutrients [54, 55]. In the case of MCHC, the decrease in organisms residing in industrial zones, in the sampling of 2008, can be attributed to contamination in these places, being associated with a microcytic anemia, which could have been caused by exposure to pollutants such as heavy metals (e.g. lead) [11]. But for 2016, MCHC concentrations in
The results of the condition factor of
The estimation of the condition factor in amphibians is important to evaluate if they are under environmental stress [56]. This biomarker is commonly used to assess the general health status of aquatic and terrestrial organisms, because it is considered a non-destructive biomarker of energy reserves [57]. This is very important given that energy reserves can be used for the maintenance, development, or reproduction of amphibians. Commonly, a greater reserve of energy in organisms gives them greater resistance without food, greater survival, and better reproductive performance compared to individuals with lower reserves [58].
\nThere is very little information on the use of the condition factor in amphibians in contaminated sites. Some researchers [58] reported a decrease in the condition factor and enzymatic alterations in semi-aquatic and terrestrial frogs resident in agricultural sites, associating it with a possible activation of compensatory or detoxification systems in amphibians in the face of environmental stress or a decrease in their prey (mosquitoes) by the application of insecticides. In other organisms, such as fish and birds, the decrease in the condition factor after exposure to heavy metals and organochlorine compounds, respectively, has been reported [59, 60]. Exposure of organisms to pollutants can increase energy requirements, decrease the metabolic or nutrient assimilation rate, and even alter digestion enzymes [41, 54, 61]. This could explain the decrease in the condition factor of the resident toads of the industrial zone in our studies (both samplings), given that, as already mentioned, a greater presence of pollutants has been demonstrated in this area. Regarding the similarity found between the toads resident in the rural area of 2016 and the laboratory ones and their increase in comparison of the organisms of the rural (2008) and industrial sites (2016), another factor that could be influencing these differences could be the scarce availability of food, caused either by natural conditions or by anthropogenic conditions.
\nThe results of the correlations between the δ-ALAD enzymatic activity and the MCHC are shown in Figure 4. As observed in this figure, for the organisms of the 2008 sampling, in the rural area, there is an association between these physiological responses. This same pattern is observed considering both (total) sites in this sampling year (Figure 4A and C—2008). As previously mentioned, the relationship of the activity of this biomarker and the hematological parameters is found in the fact that the former is part of the metabolic pathway of hemoglobin, which is congruent with these results. However, when making the correlations for the toads of the 2016 sampling, only a statistically significant correlation (p < 0.05) between both biomarkers is observed for the industrial zone (Figure 4B-2016). It is important to mention that for the laboratory toads, no correlations were found between the physiological responses, besides that the values of δ-ALAD in these were found above those of Coatzacoalcos, and the hematological parameters in smaller quantity. This could support the hypothesis that organisms from this site could be producing more Hb and HT (MCHC) to defend against the effects caused by pollutants (heavy metals such as lead) found in the area, which is evident in the organisms of the rural area of the 2008 sampling. However, for the 2016 sampling, the rural area shows a decrease in the MCHC. Therefore, the hypothesis could be supported that the concentrations of lead have increased in this site and consequently the exposure, thus affecting the compensation system of the organisms in this area. In addition to confirming a chronic exposure to this pollutant.
\nCorrelations between δ-ALAD and hematologic parameters per site and per year (total) in blood of
It is important to mention that several routes and sources of exposure to lead can be found in the toads of Coatzacoalcos due to their complex life cycle. One of these can occur when the tongue of this organism catches its prey, because this organ can be in contact with the soil or sediments (which can be exposed by dredging that takes place in the area), and, as a consequence, ingest particles in which lead may be present [62]. Also, the exposure in this case could be increased by consuming preys that have been exposed to this metal and that contain it; in this case, the presence of lead has been demonstrated in insects that inhabited industrial sites [63] that could be part of the diet of the giant toad in Coatzacoalcos due to their voracious appetite [9]. Likewise, it has been demonstrated that the consumption of prey in some organisms can increase the concentrations of lead and manifest the toxic effects [64]. Therefore, this would complement the possible explanation of the decrease or increase in some physiological responses in organisms of the 2016 sampling.
\nFinally, it should be mentioned that the physiological responses quantified in
The δ-ALAD activity, the hematological parameters, and the condition factor can be considered as biomarkers of exposure and/or effect, non-destructive, in giant toads in monitoring studies in sites contaminated by heavy metals or other pollutants. Especially δ-ALAD, which could reflect a chronic exposure in organisms. On the other hand, the results found with the organisms of the lower basin of the Coatzacoalcos river could lead to the need to make a new monitoring with emphasis on the rural regions to affirm or discard out if there is an increase in the concentration of pollutants, especially Pb, its possible causes and, if this may be affecting other organisms and even the human settlements that are there. New studies carried out in this region should take into account this type of physiological responses in a battery of biomarkers that reflect the response to other pollutants already registered on the site.
\nOnce again, it was confirmed that the giant toad (
This work was supported by Fondo de Apoyo a la Investigación (C17-FAI-06-27-27) by Universidad Autónoma de San Luis Potosí and Secretaría de Educación Pública - Consejo Nacional de Ciencia y Tecnología (SEP-CONACYT-Ciencia Básica-178778). We are also grateful to the Catedras CONACyT-UASLP project (No. 553). Special thanks to Universidad Veracruzana-Campus Coatzacoalcos for the facilities granted for sampling and obtaining samples of the giant toads.
\nThe authors declare that there is no conflict of interest regarding the publication of this chapter.
Early signs and symptoms of autoimmune bullous diseases such as mucous membrane pemphigoid (MMP) or pemphigus vulgaris (PV) develop in the oral cavity in almost all cases. MMP is the most commonly recognized, followed by PV [1]. MMP is one of a group of autoimmune, subepithelial blistering diseases that predominantly affect the mucous membranes. MMP is considered to be a disease phenotype related to one or more different anti-basement membrane zone (BMZ) autoantibodies. Various components in the hemidesmosomes have been recognized as the target antigens of MMP, including bullous pemphigoid antigen 2 (BP180), bullous pemphigoid antigen 1 (BP230), laminin 332, type VII collagen, and β4 or α6 integrin subunits [2, 3, 4, 5]. Most MMP patients are in the fifth or sixth decade of life, and the majority of them are women [6, 7, 8]. Oral lesions are observed in almost all cases, and the primary lesion often appears in the oral cavity [6, 7, 8, 9, 10]. PV is an autoimmune bullous disease characterized by acantholysis and suprabasilar separation in the epithelium of skin and/or mucous membranes. The main target antigen of PV is desmoglein (Dsg) 3, which is a constituent of desmosomes on the keratinocyte [11, 12]. Almost all PV patients with lesions limited to the oral mucosa have circulating autoantibodies to Dsg3 [12, 13, 14, 15]. PV patients with lesions in the oral mucosa and skin also have Dsg1 autoantibodies, the main antigen of pemphigus foliaceus [12, 14, 15]. PV can develop at any age, but is most commonly observed in middle-aged and elderly individuals [16, 17, 18, 19]. Early signs and symptoms of PV develop in the oral cavity in about 80% of patients [19].
\nSince patients with MMP or PV frequently experience only oral symptoms of pain and discomfort, they often visit the dentist or periodontist before other health care workers [20, 21, 22]. Desquamative gingivitis (DG) is a condition characterized by painful erythematous gingiva not resulting from dental plaque, sloughing of gingival tissues, erosions and ulcerations of the gingival epithelium and bulla formation on the gingiva [23, 24, 25, 26]. It is a clinical manifestation common to several diseases or disorders [23, 24, 25, 26]. Most DG patients are caused by mucocutaneous diseases. The differential diagnoses include oral lichen planus, MMP, and PV [24]. MMP is responsible for 35–48% and PV for 3–15% of DG [26]. Contact allergic reactions to various oral hygiene products, dental materials, or food flavoring and preservatives have also been reported in the differential diagnosis of DG [23, 24]. Gingival desquamation is a prominent clinical feature, and Nikolsky’s sign often shows a positive reaction in DG caused by autoimmune bullous diseases [21]. This sign involves the application of a firm sliding or rubbing force on normal-appearing gingiva, inducing epithelial desquamation [21, 27].
\nAlthough an accurate diagnosis of oral mucosal disease or disorder causing DG is required to provide proper treatment, it is almost impossible to do so based solely on clinical appearance. Therefore, histopathological examination and direct immunofluorescence (DIF) testing are often required to establish the final diagnosis [24]. The specific disease or disorder causing DG, the severity of the DG lesions, the presence or absence of extraoral lesions, and the medical history of the patient are the key factors in determining the selection of a topical or systemic treatment [10, 23, 24]. In some patients, DG can be successfully managed with moderate to very high-potency topical corticosteroids combined with effective plaque control. Patients with severe and/or multiple oral lesions, or recalcitrant lesions, may need aggressive systemic treatment. The presence of extraoral lesions also may require systemic treatment for effective management. Although scarring with MMP is rarely a feature of the oral mucosa, conjunctival scarring may lead to blindness if not treated aggressively [28, 29]. Airway obstruction due to laryngeal scarring is a rare condition, but it may occasionally be a fatal complication [30, 31]. PV is a life-threatening condition if left untreated [32], so it is important to diagnose and treat it in its early stages. This study describes in detail the clinical and diagnostic findings of MMP or PV as a common oral manifestation of autoimmune bullous diseases.
\nThis is a retrospective study of 37 patients with MMP (24 cases) or PV (13 cases) who were seen by the authors at Nihon University, School of Dentistry at Matsudo between 2001 and 2017. Patients participating in the study included 10 males and 27 females, aged 24–83 years, with a mean age of 58.4 years. The medical records included information on each patient’s clinical features, intraoral site involvement, presence or absence of extraoral lesions, duration from the onset of symptoms until presentation for diagnosis, and diagnostic information provided to the patient. A biopsy was obtained that included perilesional tissue and was then submitted for routine histopathology and DIF study for each of the 37 patients. DIF study was performed using conjugates for immunoglobulin (Ig) G, IgA, IgM, complement C3, and fibrinogen. Patients were diagnosed with MMP or PV through clinical examination supported by histologic diagnosis and DIF testing [24, 25, 33]. Some of the 37 patients presented in this study have been previously reported [9, 13, 14, 21, 34]. The current study was approved by the institutional review board (Ethics Committee Approval no. EC14-011-1).
\nThe results summarizing the intraoral involvement in 37 patients are shown in Table 1. All 37 patients described DG lesions including erythema, erosions, ulcerations, and epithelial desquamation (Figures 1–4). The oral lesions were confined to gingiva in 70.3% of patients. In a small number of patients, ulcers and erosions were also observed in the buccal mucosa, soft palate or tongue (Figures 5–7). Table 2 summarizes the diagnostic pattern in the 37 patients. Diagnosis delays of more than 6 months were experienced by 30.8% of the PV patients and 54.2% of the MMP patients. 16.7% of patients with MMP were delayed for more than 12 months from onset to diagnosis. The results summarizing the characteristics of the biopsy findings in these 37 patients are shown in Table 3. Subepithelial separation was observed in the H&E-stained section in 20 patients with MMP (Figure 8). Three MMP samples showed nonspecific inflammation, and one MMP sample was nondiagnostic because of a total lack of the epithelium in the H&E-stained section. In contrast, acantholysis and a suprabasilar separation in the epithelium were observed in the H&E-stained section in all 13 PV patients (Figure 9). In the DIF testing, all 37 samples showed positive staining at the BMZ (MMP Figure 10) or at the intercellular space (PV Figure 11).
\nSite | \nMMP (n = 24) | \nPV (n = 13) | \nTotal (n = 37) | \n
---|---|---|---|
Gingiva only | \n17 (70.8%) | \n9 (69.2%) | \n26 (70.3%) | \n
Gingiva + buccal mucosa + tongue | \n1 (4.2%) | \n2 (15.4%) | \n3 (8.1%) | \n
Gingiva + buccal mucosa + soft palate | \n0 (0%) | \n1 (7.7%) | \n1 (2.7%) | \n
Gingiva + buccal mucosa | \n2 (8.3%) | \n1 (7.7%) | \n3 (8.1%) | \n
Gingiva + soft palate | \n3 (12.5%) | \n0 (0%) | \n3 (8.1%) | \n
Gingiva + tongue | \n1 (4.2%) | \n0 (0%) | \n1 (2.7%) | \n
Intraoral site involvement in 37 patients.
Desquamative gingivitis associated with mucous membrane pemphigoid. Diffuse erythematous lesions on the gingiva.
Desquamative gingivitis associated with pemphigus vulgaris. Patchy erythematous lesions were found on the gingiva.
Pseudomembrane-covered erosion of the gingiva associated with mucous membrane pemphigoid.
Localized erosions of the gingiva associated with pemphigus vulgaris.
Pseudomembrane-covered erosion of the buccal mucosa associated with mucous membrane pemphigoid.
Localized erosions of the palatal mucosa associated with pemphigus vulgaris.
Desquamative lesion of the tongue associated with pemphigus vulgaris.
Diagnostic delay | \nDiagnosis | \n||
---|---|---|---|
MMP (n = 24) | \nPV (n = 13) | \nTotal (n = 37) | \n|
≤6 months | \n11 (45.8%) | \n9 (69.2%) | \n20 (54.1%) | \n
7–12 months | \n9 (37.5%) | \n4 (30.8%) | \n13 (35.1%) | \n
>12 months | \n4 (16.7%) | \n0 (0%) | \n4 (10.8%) | \n
Diagnostic pattern in 37 patients.
\n | MMP (n = 24) | \nPV (n = 13) | \n
---|---|---|
Subepithelial separation | \n20 | \n0 | \n
Acantholysis and suprabasilar separation | \n0 | \n13 | \n
Non-specific | \n3 | \n0 | \n
Non-diagnostic | \n1 | \n0 | \n
Positive | \n24* | \n13** | \n
Negative | \n0 | \n0 | \n
Biopsy findings in 37 patients.
A linear BMZ deposition of varying combinations of IgG, IgA, fibrinorgen and complement C3.
An epithelial intercellular deposition of IgG and complement C3.
Hematoxylin-eosin-stained section of mucous membrane pemphigoid. A subepithelial separation was found.
Hematoxylin-eosin-stained section of pemphigus vulgaris. Acantholysis and a suprabasilar separation in the epithelium were observed.
Direct immunofluorescence of the mucous membrane pemphigoid. A linear deposition of IgG at the basement membrane zone was recognized.
Direct immunofluorescence of pemphigus vulgaris. An intercellular deposition of IgG was evident.
After a diagnosis of MMP or PV, patients were advised to confirm the presence or absence of extraoral lesions by a dermatologist, otorhinolaryngologist, and ophthalmologist. Eleven (eight patients with MMP and three patients with PV) of the 37 patients (29.7%) confirmed the presence of extraoral lesions. The sites where clinical involvement was found were skin (5 patients), upper airway (10 patients), and eye (2 patients). Multiple extraoral mucosal involvements were found in four patients with MMP and two patients with PV. All patients with extraoral involvement were managed by medical specialists with systemic treatment with or without hospitalization (Figure 12a and b). Patients with exclusively oral lesions were managed at the authors’ hospital using a topical corticosteroid combined with effective plaque control. Patients were carefully monitored at 2–3 week intervals, and complete remission or minimalization of symptoms was achieved (Figure 13a and b).
\n(a) Desquamative gingivitis associated with pemphigus vulgaris. Localized erosion was observed on the palatal mucosa. Lesions were also found on the skin and upper airway. (b) Treatment response. The patient was managed by dermatologists with systemic treatment with hospitalization.
(a) Desquamative gingivitis associated with mucous membrane pemphigoid. (b) Treatment response. Desquamative gingivitis was successfully managed using a topical corticosteroid combined with effective plaque control.
The results of this study indicate that DG is an early sign of autoimmune bullous diseases such as MMP or PV. Although multiple oral sites were affected in some patients, 70.3% of the oral lesions were confined only to the gingiva, and DG was the only manifestation of the diseases. Data from this study indicate 70.8% of MMP patients had oral lesions confined only to the gingiva. This figure agrees with other reports [8, 25]. In contrast, in the present study, the frequency of oral lesions limited to the gingiva in PV patients is higher (69.2%) than previous reports (3–30%) [17, 18, 19, 25, 35]. The oral lesions of PV are usually multiple, typically in the buccal mucosa and soft palate [17, 18]. This disparity may be due to the selected bias due to an author’s speciality (periodontist), as the patients may have been presenting for treatment of gingival lesions. Another limitation is that the number of PV cases is limited.
\nNearly half (45.9%) of the patients in this study had experienced diagnostic delays longer than 6 months, indicating that early diagnosis of autoimmune bullous diseases in the oral cavity was still difficult. According to the survey of Sirois et al. [19] diagnostic delays greater than 6 months were common in oral PV, but 100% of cutaneous PV patients were correctly diagnosed within 6 months. Mobini et al. [36] reported that the mean period from onset of the disease until diagnosis was 7.57 months in patients with MMP. In this study, diagnosis was delayed more than 1 year for 16.7% of the MMP patients. This may be related to the characteristics of MMP. The initial symptoms of MMP often tend to undergo repeated episodes of onset and remission, and spontaneous remission was also observed in a few MMP patients. Furthermore, obtaining diagnostic biopsies from MMP patients is technically challenging. An inadequate surgical technique or surgical site selection, or improper tissue handling may easily lead to the loss of the gingival epithelium [25, 34, 37]. Four of the patients diagnosed with MMP at the author’s clinic were previously biopsied at other facilities, but diagnosis was not rendered. This may be because the intact epithelium was not retained in those specimens. To avoid this problem, the authors reported a stab-and-roll biopsy technique designed to maintain the gingival epithelium for patients with DG [25, 34]. In this technique, more than 90% of biopsies were obtained exhibiting successful retention of intact epithelium, and all biopsies offered diagnostic support [34]. This biopsy technique may facilitate early diagnosis and treatment of diseases causing DG.
\nTo establish a correct diagnosis of DG-associated diseases, conventional microscopic examination and DIF testing are essential. In particular, DIF testing is the gold standard used to diagnose autoimmune bullous diseases and is required for a definitive diagnosis [25, 33, 38]. In this study, all 37 autoimmune bullous diseases showed positive DIF staining. In H&E findings, acantholysis and a suprabasilar separation in the epithelium was observed in all 13 patients with PV. In contrast, a subepithelial separation was observed in 20 patients with MMP (83.3%). Since epithelial acantholysis is quite distinctive, it may be possible that correct diagnosis to be rendered based on H&E findings alone [38]. In contrast, the subepithelial separation, which is a characteristic of MMP patients, is a nondiagnostic finding as it is also found in other vesiculobullous diseases. Therefore, the international expert consensus on MMP does not consider results from conventional microscopic studies as an absolute criterion for the diagnosis [2].
\nIn this study, extraoral lesions were confirmed in 11 of the 37 cases (29.7%) at the time of diagnosis. Since the oral cavity is the site of most problematic lesions, the patients came to the author’s hospital first. Concomitant extraoral lesions were more common in MMP, and the patients tended to be affected in multiple mucosal sites or skin. Multiple target antigens of MMP were identified in BMZ components by the appearance of circulating autoantibodies in the patients’ serum [2, 3, 4, 5]. Therefore, it is currently believed that MMP is not a single entity but has distinct clinical subsets. For example, some MMP patients have involvement limited to the conjunctiva. They are referred to as having ocular cicatricial pemphigoid [39, 40]. Similarly, Mobini et al. [36] proposed that the MMP lesions confined only to the oral cavity are called “oral pemphigoid.” In these clinical subsets, other mucous membranes and/or skin are not involved at long-term follow-up [4, 36, 41]. Di Zenzo et al. [42] pointed out in their review that it is important to know whether the exclusive oral lesion is only a stage of the course of MMP or if it represents the phenotype of a distinct clinical entity. In some long-term studies, MMP patients with exclusively oral lesions show that lesions do not develop in other mucous membranes and/or skin during follow-up [4, 36, 41]. In contrast, other studies indicate that MMP patients with initial oral lesions have a risk of developing ocular involvement with a calculated incidence rate from 0.03 to 0.05 persons per year [28, 29]. Several authorities suggest that early diagnosis of ocular MMP lesions is essential to successful management yet early signs of MMP may not be readily evident to other healthcare workers. Consequently, it may be advisable to refer any MMP patient to an ophthalmologist for immediate and long-term follow-up. Although there is a possibility that the clinical subset of MMP is classified based on the antibody profiles in their serum [3], at present, there is no known correlation between antigen-specific autoantibodies and the prognosis of disease [2].
\nPV frequently begins with oral lesions and later progresses to skin lesions [19]. Patients with PV with exclusively oral lesions should be followed closely and referred to other experts immediately if they develop signs or symptoms of lesions elsewhere on the body. Although the necessity of systemic therapy is decided with reference to the circulating anti-Dsg antibody titer in some cases, the therapeutic approach to PV is largely based on expert opinion rather than empirical evidence [43, 44, 45, 46]. The monitoring of PV disease activity is mainly based on clinical findings at the present moment [43, 45, 46]. In any case, PV limited to oral cavity should be followed for a long period of time and perhaps indefinitely.
\nDG is an early sign of autoimmune bullous diseases such as MMP or PV in the oral cavity. In this study, about 70% of the oral lesions are confined to the gingiva, and DG was the only manifestation of the diseases. To establish a correct diagnosis of DG caused by autoimmune bullous diseases, conventional microscopic examination and DIF testing are essential. In particular, DIF testing is the gold standard used to diagnose of MMP or PV. Since some lesions remain limited to the oral cavity for a long period of time, patients diagnosed with MMP or PV should be closely followed because they must be immediately referred to other experts when they develop lesions on parts of their body other than the oral cavity. The oral healthcare provider should collaborate with other healthcare experts including dermatologists, ophthalmologists, and otolaryngologists to evaluate and manage patients with autoimmune bullous diseases in the oral cavity.
\nThis study was supported by a Grant-in-Aid for Young Researcher Scientists, Nihon University School of Dentistry at Matsudo (2015). The authors report no conflicts of interest related to this study.
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The PA industry is spread out worldwide in Europe, Asia and America, including countries that operate phosphate rock (PR) mines and produce PA, phosphatic fertilizers and phosphate-based products.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Benjamín Valdez Salas, Michael Schorr Wiener and Juan Ricardo\nSalinas Martinez",authors:[{id:"16436",title:"Dr.",name:"Michael",middleName:null,surname:"Schorr",slug:"michael-schorr",fullName:"Michael Schorr"}]},{id:"54906",doi:"10.5772/67926",title:"Purification of Phosphoric Acid by Liquid‐Liquid Equilibrium",slug:"purification-of-phosphoric-acid-by-liquid-liquid-equilibrium",totalDownloads:1681,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Various ternary and quaternary liquid‐liquid phase equilibrium data for water + phosphoric acid + solvent(s) have been reported. Salting‐out, solvent, and temperature effects on the binodal curve and the tie lines have been highlighted and the capability of solvents with different functional groups to extract phosphoric acid from water has been compared. Studying of influence of magnetic, electromagnetic, and ultrasonic fields on the separation factors and distribution coefficients of aqueous phosphoric acid mixtures has been proposed. Moreover, a summary of the optimized binary interaction values, which resulted from non‐random two‐liquid (NRTL) and universal quasi‐chemical (UNIQUAC) thermodynamic models using genetic algorithm (GA), bee algorithm (BA), and simulated annealing (SA), has been presented. Group method of data handling (GMDH) and linear solvation energy relationship (LSER) methods for the correlation of experimental liquid‐liquid equilibrium (LLE) data have been used.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Khatereh Bahrpaima",authors:[{id:"193562",title:"Dr.",name:"Khatereh",middleName:null,surname:"Bahrpaima",slug:"khatereh-bahrpaima",fullName:"Khatereh Bahrpaima"}]},{id:"55219",doi:"10.5772/intechopen.68567",title:"Occupational, Public and Environmental Radiological Impact Caused by the Phosphoric Acid Industry: The Case of Huelva (Spain)",slug:"occupational-public-and-environmental-radiological-impact-caused-by-the-phosphoric-acid-industry-the",totalDownloads:1355,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"The production of phosphate fertilizers usually uses as raw material sedimentary phosphate rock, which contains enhanced concentrations from U‐series radionuclides about 10–100 times higher than unperturbed soils. This fact implies the need for evaluating the radiological implications of this activity. In our case, the study has been performed in a large fertilizer industrial complex located at Huelva town (SW of Spain), where sedimentary phosphate rock has been processed since 1965 to 2010, generating annually an average of about 2.5 million tons of a by‐product called phosphogypsum (PG), which has been stored in big stacks 1 km away from Huelva city, covering 1000 ha. The fluxes of the radionuclides of interest along the production process and the effective doses received by the workers have been determined. In addition, the radioecological impact associated to the waste management strategy followed has been evaluated.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"José Luis Guerrero‐Márquez, Fernando Mosqueda Peña, Juan\nMantero, Guillermo Manjón, Rafael García‐Tenorio and Juan Pedro\nBolívar",authors:[{id:"57724",title:"Dr.",name:"Guillermo",middleName:null,surname:"Manjon",slug:"guillermo-manjon",fullName:"Guillermo Manjon"},{id:"111020",title:"Prof.",name:"Juan Pedro",middleName:null,surname:"Bolivar",slug:"juan-pedro-bolivar",fullName:"Juan Pedro Bolivar"},{id:"111022",title:"Prof.",name:"Rafael",middleName:null,surname:"Gacia Tenorio",slug:"rafael-gacia-tenorio",fullName:"Rafael Gacia Tenorio"},{id:"193940",title:"Dr.",name:"Fernando",middleName:null,surname:"Mosqueda",slug:"fernando-mosqueda",fullName:"Fernando Mosqueda"},{id:"193941",title:"Dr.",name:"Juan",middleName:null,surname:"Mantero",slug:"juan-mantero",fullName:"Juan Mantero"},{id:"193942",title:"Ph.D. Student",name:"José Luis",middleName:null,surname:"Guerrero-Márquez",slug:"jose-luis-guerrero-marquez",fullName:"José Luis Guerrero-Márquez"}]},{id:"55434",doi:"10.5772/intechopen.68236",title:"Diluted Thermopressurized Phosphoric Acid: A Gentle Proton Donor for Polysaccharide Acid Depolymerization and (Bio)processing",slug:"diluted-thermopressurized-phosphoric-acid-a-gentle-proton-donor-for-polysaccharide-acid-depolymeriza",totalDownloads:1710,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Phosphorus is a very important element for several metabolic pathways in all living organisms as exemplified by DNA, RNA, glucose and fructose-P, and adenosine triphosphate (ATP). The whole metabolism of phosphate in any living organism involves the catalysis carried out by many enzymes, such as kinases, pyrophosphorylases, isomerases, and phosphatases. Symptoms of hypophosphatemia include neurological dysfunction and disruption of muscle and blood cells and could be caused by malnutrition, failure to absorb phosphate, and metabolic syndromes. Phosphoric acid is widely used as an acidifying agent in a variety of pharmaceutical formulations as an acidulant, flavor, and synergistic antioxidant and sequestering. At the laboratorial and industrial territories, due to safety precautions, phosphoric acid may be considered a valid acid alternative for stronger and risky acids such as sulfuric, hydrochloric, and nitric acids. Furthermore, phosphoric acid, among the mineral acids, is less corrosive for steel and all goods made therefrom. Taking into account all these favorable arguments, the applied research at our laboratory (LQBB) is focused, with success, in the utilization of much diluted and moderately thermopressurized phosphoric acid (o-PA) in the pretreatment of polysaccharides for many biotechnological, as oligosaccharides production, important prebiotics for the human gastrointestinal tract.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"José Domingos Fontana, Marcela Tiboni and Heidegrid Siebert\nKoop",authors:[{id:"192320",title:"Prof.",name:"José Domingos",middleName:null,surname:"Fontana",slug:"jose-domingos-fontana",fullName:"José Domingos Fontana"},{id:"195692",title:"Dr.",name:"Marcela",middleName:null,surname:"Tiboni",slug:"marcela-tiboni",fullName:"Marcela Tiboni"},{id:"195694",title:"Dr.",name:"Heidegrid",middleName:null,surname:"Siebert Koop",slug:"heidegrid-siebert-koop",fullName:"Heidegrid Siebert Koop"}]},{id:"56294",doi:"10.5772/intechopen.68658",title:"Recent Trends in Phosphatase-Mediated Bioremediation",slug:"recent-trends-in-phosphatase-mediated-bioremediation",totalDownloads:2117,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Industrial effluents from tanneries and electroplating industries from small‐ and large‐scale sector industrial plants contain substantial amount of toxic heavy metal, which pollutes rivers and lakes, land, air and sea leading to imbalance of ecosystem and certain health issues to humans, animals as well as plants. The worldwide environmental regulations stipulate the reduction of heavy metals in the effluents to permissible levels before discharging into water bodies. Enzyme‐mediated precipitation of heavy metals affords a novel eco‐friendly method for remediation of toxic heavy metals from various industrial effluents like tannery, electroplating and dye industries. This chapter has paid attention to bacterial alkaline phosphatase (BAP) from Escherichia coli C90 and calf‐intestinal alkaline phosphatase (CIAP), which catalyses phospho mono‐ and diesters and produces inorganic phosphate (Pi). The Pi thus generated precipitates the heavy metals as metal‐phosphate complexes. The kinetic behaviour of both the enzymes with para‐nitrophenyl phosphate, ascorbic acid 2‐phosphate and α‐naphthyl phosphate was investigated at various pH regimes from 8 to 11. The chapter also explains in detail the descriptive information on the capability of BAP‐ and CIAP‐mediated precipitation of heavy metals, which is desirable and convenient method for the toxic heavy metals such as chromium, cadmium, nickel and cobalt.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Gouri Chaudhuri, Uma Selvaraj, Venu Babu and Richard W.\nThilagaraj",authors:[{id:"192857",title:"Dr.",name:"Richard",middleName:null,surname:"Thilagaraj",slug:"richard-thilagaraj",fullName:"Richard Thilagaraj"},{id:"195962",title:"Dr.",name:"P. Venu",middleName:null,surname:"Babu",slug:"p.-venu-babu",fullName:"P. Venu Babu"},{id:"195963",title:"Dr.",name:"Gouri",middleName:null,surname:"Chaudhuri",slug:"gouri-chaudhuri",fullName:"Gouri Chaudhuri"},{id:"195964",title:"Ms.",name:"Uma",middleName:null,surname:"Selvaraj",slug:"uma-selvaraj",fullName:"Uma Selvaraj"}]}],mostDownloadedChaptersLast30Days:[{id:"56162",title:"Phosphoric Acid Industry: Problems and Solutions",slug:"phosphoric-acid-industry-problems-and-solutions",totalDownloads:5178,totalCrossrefCites:2,totalDimensionsCites:9,abstract:"Phosphoric acid (PA) is an important industrial chemical used as an intermediate in the fertilizer industry, for metal surface treatment in the metallurgical industry and as an additive in the food industry. The PA industry is spread out worldwide in Europe, Asia and America, including countries that operate phosphate rock (PR) mines and produce PA, phosphatic fertilizers and phosphate-based products.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Benjamín Valdez Salas, Michael Schorr Wiener and Juan Ricardo\nSalinas Martinez",authors:[{id:"16436",title:"Dr.",name:"Michael",middleName:null,surname:"Schorr",slug:"michael-schorr",fullName:"Michael Schorr"}]},{id:"55389",title:"Thermochemistry and Kinetics of the Reactions of Apatite Phosphates with Acid Solutions (II)",slug:"thermochemistry-and-kinetics-of-the-reactions-of-apatite-phosphates-with-acid-solutions-ii-",totalDownloads:1877,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The principal material in the phosphate ores is composed of calcium fluorapatite Ca10(PO4)6F2, in which the various components have been partially substituted by magnesium, sodium, carbonate, and hydroxyl ions. These substitutions affect the stability of the material and its reactivity toward the acid attack. The present chapter reports the influence of carbonates and magnesium on these properties. Using different calorimeters, dissolution experiments of carbonated and noncarbonated Ca and Ca/Mg apatites were carried out in acid solutions leading to thermochemical quantities. The results show that substitution of carbonate for F ions in the channel (to get A-type carbonate F-apatites) results in increasing the stability of the edifice, while substitution of CO3 for PO4 in fluor- or hydroxyapatites (to get B-type apatites) leads to a decrease in stability. The latter phenomenon was also observed when substituting magnesium for calcium in F-apatites. The presence of the former in the apatite structure results in an increase of the speed of dissolution in acid solution that is enhanced when carbonate is also replacing phosphate groups. Dissolution mechanism of synthesized Ca/Mg F-apatites seems to be a one-step process, while dissolution of a Gafsa (TN) natural phosphate to get superphosphate fertilizer is more complex.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Mohamed Jemal",authors:[{id:"15449",title:"Dr.",name:"Mohamed",middleName:null,surname:"Jemal",slug:"mohamed-jemal",fullName:"Mohamed Jemal"}]},{id:"55219",title:"Occupational, Public and Environmental Radiological Impact Caused by the Phosphoric Acid Industry: The Case of Huelva (Spain)",slug:"occupational-public-and-environmental-radiological-impact-caused-by-the-phosphoric-acid-industry-the",totalDownloads:1355,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"The production of phosphate fertilizers usually uses as raw material sedimentary phosphate rock, which contains enhanced concentrations from U‐series radionuclides about 10–100 times higher than unperturbed soils. This fact implies the need for evaluating the radiological implications of this activity. In our case, the study has been performed in a large fertilizer industrial complex located at Huelva town (SW of Spain), where sedimentary phosphate rock has been processed since 1965 to 2010, generating annually an average of about 2.5 million tons of a by‐product called phosphogypsum (PG), which has been stored in big stacks 1 km away from Huelva city, covering 1000 ha. The fluxes of the radionuclides of interest along the production process and the effective doses received by the workers have been determined. In addition, the radioecological impact associated to the waste management strategy followed has been evaluated.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"José Luis Guerrero‐Márquez, Fernando Mosqueda Peña, Juan\nMantero, Guillermo Manjón, Rafael García‐Tenorio and Juan Pedro\nBolívar",authors:[{id:"57724",title:"Dr.",name:"Guillermo",middleName:null,surname:"Manjon",slug:"guillermo-manjon",fullName:"Guillermo Manjon"},{id:"111020",title:"Prof.",name:"Juan Pedro",middleName:null,surname:"Bolivar",slug:"juan-pedro-bolivar",fullName:"Juan Pedro Bolivar"},{id:"111022",title:"Prof.",name:"Rafael",middleName:null,surname:"Gacia Tenorio",slug:"rafael-gacia-tenorio",fullName:"Rafael Gacia Tenorio"},{id:"193940",title:"Dr.",name:"Fernando",middleName:null,surname:"Mosqueda",slug:"fernando-mosqueda",fullName:"Fernando Mosqueda"},{id:"193941",title:"Dr.",name:"Juan",middleName:null,surname:"Mantero",slug:"juan-mantero",fullName:"Juan Mantero"},{id:"193942",title:"Ph.D. Student",name:"José Luis",middleName:null,surname:"Guerrero-Márquez",slug:"jose-luis-guerrero-marquez",fullName:"José Luis Guerrero-Márquez"}]},{id:"56294",title:"Recent Trends in Phosphatase-Mediated Bioremediation",slug:"recent-trends-in-phosphatase-mediated-bioremediation",totalDownloads:2117,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Industrial effluents from tanneries and electroplating industries from small‐ and large‐scale sector industrial plants contain substantial amount of toxic heavy metal, which pollutes rivers and lakes, land, air and sea leading to imbalance of ecosystem and certain health issues to humans, animals as well as plants. The worldwide environmental regulations stipulate the reduction of heavy metals in the effluents to permissible levels before discharging into water bodies. Enzyme‐mediated precipitation of heavy metals affords a novel eco‐friendly method for remediation of toxic heavy metals from various industrial effluents like tannery, electroplating and dye industries. This chapter has paid attention to bacterial alkaline phosphatase (BAP) from Escherichia coli C90 and calf‐intestinal alkaline phosphatase (CIAP), which catalyses phospho mono‐ and diesters and produces inorganic phosphate (Pi). The Pi thus generated precipitates the heavy metals as metal‐phosphate complexes. The kinetic behaviour of both the enzymes with para‐nitrophenyl phosphate, ascorbic acid 2‐phosphate and α‐naphthyl phosphate was investigated at various pH regimes from 8 to 11. The chapter also explains in detail the descriptive information on the capability of BAP‐ and CIAP‐mediated precipitation of heavy metals, which is desirable and convenient method for the toxic heavy metals such as chromium, cadmium, nickel and cobalt.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"Gouri Chaudhuri, Uma Selvaraj, Venu Babu and Richard W.\nThilagaraj",authors:[{id:"192857",title:"Dr.",name:"Richard",middleName:null,surname:"Thilagaraj",slug:"richard-thilagaraj",fullName:"Richard Thilagaraj"},{id:"195962",title:"Dr.",name:"P. Venu",middleName:null,surname:"Babu",slug:"p.-venu-babu",fullName:"P. 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Symptoms of hypophosphatemia include neurological dysfunction and disruption of muscle and blood cells and could be caused by malnutrition, failure to absorb phosphate, and metabolic syndromes. Phosphoric acid is widely used as an acidifying agent in a variety of pharmaceutical formulations as an acidulant, flavor, and synergistic antioxidant and sequestering. At the laboratorial and industrial territories, due to safety precautions, phosphoric acid may be considered a valid acid alternative for stronger and risky acids such as sulfuric, hydrochloric, and nitric acids. Furthermore, phosphoric acid, among the mineral acids, is less corrosive for steel and all goods made therefrom. Taking into account all these favorable arguments, the applied research at our laboratory (LQBB) is focused, with success, in the utilization of much diluted and moderately thermopressurized phosphoric acid (o-PA) in the pretreatment of polysaccharides for many biotechnological, as oligosaccharides production, important prebiotics for the human gastrointestinal tract.",book:{id:"5595",slug:"phosphoric-acid-industry-problems-and-solutions",title:"Phosphoric Acid Industry",fullTitle:"Phosphoric Acid Industry - Problems and Solutions"},signatures:"José Domingos Fontana, Marcela Tiboni and Heidegrid Siebert\nKoop",authors:[{id:"192320",title:"Prof.",name:"José Domingos",middleName:null,surname:"Fontana",slug:"jose-domingos-fontana",fullName:"José Domingos Fontana"},{id:"195692",title:"Dr.",name:"Marcela",middleName:null,surname:"Tiboni",slug:"marcela-tiboni",fullName:"Marcela Tiboni"},{id:"195694",title:"Dr.",name:"Heidegrid",middleName:null,surname:"Siebert Koop",slug:"heidegrid-siebert-koop",fullName:"Heidegrid Siebert Koop"}]}],onlineFirstChaptersFilter:{topicId:"490",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. 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He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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