Characteristics of the radioisotopes used in synovectomy.
\r\n\tAlthough the microorganism was later described by several other researchers with multiple synonyms, Escherich was recognized as the first, establishing the definitive name of the microbe as Escherichia coli in 1954.
\r\n\tIn 1933, Alfred Adam showed that certain serotypes of "dyspepsia Koli" (as he called the diarrheagenic E. coli strains) were implicated in epidemics of pediatric diarrhoea. In 1944, Kauffman proposed a classification scheme that is still in use today for the purpose of differentiating commensal types from pathogens and subclassifying them.
\r\n\tEscherichia coli, in its natural habitat, lives in the intestines of most healthy mammals. It is the main facultative anaerobic organism of the digestive system. In healthy individuals, that is, if the bacterium does not acquire genetic elements that encode virulent factors, the bacterium acts as a commensal forming part of the intestinal microbiota and thus helping the absorption of nutrients.
\r\n\tIn humans, E. coli colonizes the gastrointestinal tract of a neonate by adhering to the mucus of the large intestine within a few hours of birth. Since then, it remains in a relationship of mutual benefit. However, these commensal strains can cause infections in immunosuppressed patients.
\r\n\r\n\tPathogenic strains of E. coli, on the other hand, as soon as they colonize a healthy host, can cause infections of varying severity in the intestine, urinary tract, meningitis, and sepsis, among other infections.
\r\n\tDiarrhea caused by pathogenic strains of E. coli is an important cause of death in children under 5 years of age, especially in sub-Saharan Africa and South Asia, where it is one of the four most important causes of moderate and severe diarrhea, potentially lethal An increase in mortality is associated with enteropathogenic strains.
\r\n\tUrinary tract infections are more common in women because of the short length of the urethra (25 to 50 mm) compared to men (about 15 cm). Among the elderly, urinary infections tend to be of the same proportion between men and women.
\r\n\tBecause the bacteria invariably enter the urinary tract through the urethra (an ascending infection), poor hygiene habits can predispose to infection; however, other factors become important, such as pregnancy, benign or malignant hypertrophy of the prostate, and in In many cases, the initiating event of the infection is unknown. Although ascending infections are the cause of lower urinary tract infections and cystitis, this is not necessarily the cause of upper infections such as pyelonephritis, which may have a hematogenous origin.
Alginic acid (Alg) is a polysaccharide derived from algae. Sodium alginate (Na-Alg) is commonly used in foodstuffs as a thickening agent and stabilizer, and is also used as a health food to suppress weight gain and lower blood cholesterol (Cho) [1, 2, 3, 4]. In addition, Na-Alg has a protective action on the gastric mucosa [5, 6]. Moreover, when Na-Alg is ingested prior to exposure to strontium (Sr), Sr accumulation in the human body is decreased [7]. However, the sodium salt of Alg can potentially cause hypertension, a major risk factor for dyslipidemia and arteriosclerosis [8]. Therefore, if the calcium salt (Ca-Alg) is as effective as, or superior to, Na-Alg, it might prove to be of greater benefit.
In this chapter, focusing on our own work on Ca-Alg, we will firstly describe how Alg enhances excretion and reduces absorption of Sr and cesium (Cs) in rats. Secondly, we discuss the relationship between the physical parameters of various metal ions and their binding affinity to Alg. Thirdly, we describe the Cho-lowering effect of Ca-Alg, as well as the reducing effect of Ca-Alg on blood triglyceride (TG) levels, which leads to reduced accumulation of fat in the liver and whole body in rats. Finally, we describe how Ca-Alg in food (noodles) moderates the postprandial blood glucose level in rats and humans and we discuss the mechanism of this effect.
Although several years have passed since the nuclear power plant accident following a severe earthquake in Japan in March 2011, public unease over the possible presence of radioactive materials in foods remains. As we anticipated that foods or medicines containing Alg would help to reduce potential harmful effects, we investigated the effect of Alg on the absorption and excretion of Sr and Cs, whose radioactive isotopes have long half-lives (90Sr 28.8 years, 137Cs 30.17 years). Specifically, we examined and compared the effects of Na-Alg and Ca-Alg on the absorption and excretion of Sr and Cs in rats, as well as investigating their safety [9].
Initially, we examined the adsorption of Sr and Cs by water-soluble Na-Alg. We found that Sr alone was adsorbed by Na-Alg in a concentration-dependent manner, as was Cs alone. On the other hand, when a mixture of Sr and Cs was used, adsorption of Cs by Na-Alg was lower than in the case of Cs alone, whereas adsorption of Sr by Na-Alg was the same as with Sr alone. Thus, both Sr and Cs were concentration-dependently adsorbed by Na-Alg, but adsorption of Cs by Na-Alg was partly blocked in the presence of Sr.
Next, rats were randomized into control (normal diet), Na-Alg, and Ca-Alg groups, and the changes of native Sr and Cs concentrations in plasma were measured after 2 weeks. In the groups fed Na-Alg and Ca-Alg, the Sr concentrations were significantly decreased to 65 and 63% at 1 week, and 77 and 66% at 2 weeks, respectively, compared with the control group. On the other hand, Cs concentration was significantly reduced (to 60% of the control) only at 2 weeks in the Ca-Alg group. Histopathological observation revealed mineral deposition, due to excessive ingestion of sodium, in the pelvic epithelium of the kidney in the Na-Alg group, and epithelial hyperplasia was observed around the deposits. In contrast, no abnormality at all was detected in the Ca-Alg group. These results indicate that Ca-Alg would be safer than Na-Alg if taken daily for protection against radiation damage.
We also randomized rats into control, Na-Alg, and Ca-Alg groups, and administered SrCl2 or CsCl solution. The maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration curve for 3 hours after administration (AUC0-3 hours) were calculated from the observed data by subtracting the values before administration. When SrCl2 solution was orally administered in the Na-Alg and Ca-Alg groups, absorption of Sr was significantly decreased in comparison with the control group. In the Ca-Alg group, Cmax and AUC0–3 hours were significantly lower than in the control group after oral administration of CsCl solution. No significant difference of Cs plasma concentration profile between the control and Na-Alg groups was observed. Overall, the data suggest that absorption of both Sr and Cs was reduced in the Ca-Alg group, whereas absorption of Cs was not reduced in the Na-Alg group (Figure 1).
Plasma concentration of Sr (a) or Cs (b) after oral administration of SrCl2 to rats [
It should be noted that in these studies we used 10% Na-Alg or Ca-Alg in the diet, whereas 3–4 g/body/day of Alg is typically ingested by humans as a health food [1, 10]. Clinical studies will be required to identify an appropriate level of Ca-Alg for use as a protective agent.
In the case of acute oral exposure to toxic metals, health damage can be reduced by immediate treatments such as induction of vomiting and/or the use of a laxative to promote excretion of the metal. However, in the case of chronic exposure, it is essential to use intrinsically safe absorption inhibitors and/or excretion accelerators that are suitable for long-term administration.
Although the effect of Alg on Sr or Cs absorption and excretion has already been reported, there is little information about its effect on other metals. Therefore, we investigated the relationship between the physical parameters of various metal ions, including toxic metal ions, and the binding affinity of these metal ions for Alg [11]. For this purpose, the binding constants (K, mM−1) and the binding amount with Alg were evaluated for Sr, Pb, Tb, Dy, Ca, Cd, Mg, Fe(II), Fe(III), Co, Al, Ni, Cs, Cu, Ag, Li, and K. Aqueous solutions of each metal salt and an equivalent amount of Na-Alg were mixed, and the amount of unbound metal remaining in the filtrate was determined using an atomic absorption photometer. The amount of bound metal was calculated from the amount of remaining unbound metal ion, and K values and the number of binding sites per 1 mg of Alg (n) were analyzed using double-reciprocal plots. The affinity of each metal ion for Alg was calculated by multiplying the n and
The order of K values was as follows: Sr2+ > Pb2+ > Tb3+ > Dy3+ > Ca2+ > Cd2+ > Mg2+ > Fe2+ > Fe3+ > Co2+ > Al3+ > Ni2+ > Cs+ > Cu2+ > Ag+ > Li+ >K+. Moreover, metal ions with high K values tended to have ionic radii within the range of about 90–120 pm. On the other hand, the order of affinity for Alg was Pb2+ > Dy3+ > Tb3+ > Sr2+ > Ca2+ > Mg2+ > Cd2+ >Fe2+,Fe3+ >Cs+ >Al3+ >Co2+ >Ni2+ >Cu2+ >Ag+ >K+ >Li+.
The
Relationships between
Overall, these results indicate that Alg would be effective as an excretion accelerator and/or absorption inhibitor for various toxic metal ions, especially divalent metals such as Pb and Cd.
It is noteworthy that the affinity between Alg and Cs is relatively small, even though we had previously shown that Ca-Alg is effective in promoting excretion and decreasing absorption of Cs in rats [9]. Therefore, not only the affinity between Alg and metals, but also other factors arising from the specific combination of Alg and metal ion, may influence excretion and/or absorption of individual metal ions in the presence of Alg.
Heart disease and cerebrovascular disease are major causes of death in developed countries, accounting for about a quarter of all deaths in Japan [12]. A major factor in their pathogenesis is believed to be dyslipidemia [13, 14, 15], which is predominantly a modern lifestyle-related disease [16, 17]. Therefore, there is considerable interest in food additives or health foods that can decrease Cho absorption or promote Cho excretion.
Since Na-Alg reduces the Cho concentration in blood [9], we focused on the Cho-lowering effect of Ca-Alg in rats fed a high-Cho diet [18]. We first examined absorption of the Cho precursor taurocholate by various types of Alg in vitro, using Na-Alg instead of Ca-Alg, since Na-Alg is water-soluble. We found that high-molecular-weight, guluronic acid-rich (HMW-G) Na-Alg showed the greatest adsorption of taurocholate, and so we selected Ca-Alg HMW-G for the following in vivo study.
Rats were fed a high-Cho diet with or without 0.5–2% Ca-Alg for 2 weeks. After 14 days, the plasma concentration of Cho, the portal plasma concentration of bile acid, and the bile acid content in feces were measured. Moreover, in order to monitor safety, blood samples withdrawn after 14 days were used for the measurement of biochemical parameters. In the groups fed the high-Cho diet containing 2% Ca-Alg diet, the plasma concentration of Cho at 2 weeks was significantly lower than that of the group fed high-Cho diet alone. This result was similar to that in the group fed colestimide-containing diet as a positive control. Bile acid excretion in feces tended to increase depending on the concentration of Ca-Alg in the diet. In the group fed the 2% Ca-Alg diet, the portal plasma concentration of bile acid was significantly decreased, compared to that in the high-Cho diet group. Furthermore, the portal concentration of bile acid was significantly lowered in the 2% Ca-Alg group. There was no significant difference in weight gain or diet intake among the groups during the 2-week experimental period. Microvesicular steatosis was increased in the high-Cho diet and Ca-Alg groups, but remained within the physiological range. While several changes in biochemical parameters and histopathological findings were observed, all values remained within the physiological range (Figure 3).
Cho concentration in plasma at the end of the 2-week period with normal diet, high-Cho diet, or high-Cho diet containing Ca-Alg or colestimide to rats [
Overall, these results indicate that Ca-Alg is effective for reducing plasma Cho. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which might subsequently stimulate bile acid synthesis from Cho in the liver, leading to a decrease of Cho in plasma (Figure 4).
A possible mechanism of Cho-lowering effect of Ca-Alg [
Excess lipid is stored in the form of TG in subcutaneous and internal organs in the body, and is broken down into fatty acids as required [19]. Dyslipidemia, with increased TG and Cho levels in the blood, leads to atherosclerosis, which in turn can lead to cardiovascular disease and stroke. Accumulation of TG can also result in fatty liver disease, leading to decreased hepatic function, liver cirrhosis and potential morbidity, including myocardial infarction, cerebral infarction and angina pectoris, and eventually cancer [20, 21, 22, 23].
Since we previously observed that the TG level in blood was decreased by Ca-Alg in rats [18], we next set out to examine the effect of Ca-Alg on elevated TG levels in the blood, hepatic and total body accumulation of fat, and body weight in rats fed a TG-loaded diet for 5 weeks. We also investigated the mechanism of the TG-reducing effect of Alg in vitro [24].
Rats were randomized into five groups: a high-fat diet group (14% w/w lard, HF); 3 Ca-Alg-containing diet groups (2.5, 5 or 10% w/w Ca-Alg) and a resistant maltodextrin (RMD) diet group as a positive control (with 5% w/w RMD). The 10% Ca-Alg group showed a significant reduction of body weight increase from the 7th day. The increase of TG in blood was also significantly suppressed, and the amount of TG excreted in feces was increased. Increase of body fat mass was in the order HF > RMD > Ca-Alg 2.5% > Ca-Alg 5% > Ca-Alg 10%, while the total weight of the extracted fat tissues was significantly reduced in the RMD, 5 and 10% Ca-Alg groups. Hepatic pathology showed clear circular vacuoles apparently representing TG accumulation in the HF group, while fewer vacuoles were seen in the Ca-Alg groups.
These results suggest that Ca-Alg lowers blood TG through direct suppression of TG absorption, independently of its effect on Cho. As regards the mechanism of Ca-Alg action, hepatic pathology showed that clear circular fatty droplets presumed to represent TG accumulation were present in the HF group, but were reduced in the 10% Ca-Alg group. Interestingly, the concentrations of uric acid, allantoin and BUN in plasma were also decreased in all the Ca-Alg groups, though the mechanism involved is unclear (Figure 5).
Area under the blood concentration-time curve of TG in rats after the 5-week feeding period with high-fat diet or high-fat diet containing Ca-Alg or high-fat diet containing RMD [
We then investigated whether Alg affects lipase activity. Na-Alg was suspended in water, and diluted as required. When this solution was added to an emulsion composed of bile acid and lecithin in the presence of lipase, no decrease of lipase activity was observed, ruling out a direct effect on lipase. On the other hand, when Na-Alg was added to an emulsion composed of TG, bile acid and lecithin, the emulsion was well maintained, and a creaming phenomenon was confirmed after 5 days. When water was added to the emulsion, it disintegrated, precipitating lecithin and releasing TG on the liquid surface. These results suggest that Alg stabilizes bile acid micelles containing TG, possibly by absorbing them and forming large micelles that cannot be absorbed, or that are less vulnerable to lipases [24].
These results suggest that Ca-Alg suppresses absorption of TG, leading to reduced blood TG levels, and decreases hepatic and total body accumulation of TG, in addition to promoting excretion. These findings should help to provide a rational basis for designing future clinical trials (Figure 6).
A possible mechanism of TG-lowering effect of Ca-Alg [
Diabetics may develop serious complications such as retinopathy, nephropathy and neuropathy, in addition to myocardial infarction, cerebral infarction and so on [27, 30], even though the initial subjective symptoms may be minor. Ca-Alg is known to suppress the postprandial increase of blood glucose, and therefore may be helpful in preventing lifestyle-related diseases such as diabetes. Starch is initially decomposed to maltose in the gastrointestinal tract, mainly by α-amylase, before decomposition by α-glucosidase (maltase) to glucose. Transporters located on the cell membrane surface absorb glucose. Ca-Alg should inhibit at least one of these processes to suppress blood glucose levels since it is not absorbed from the gastrointestinal tract. We therefore chose to investigate which of these processes is inhibited by Ca-Alg, and the optimal amount and particle size of Ca-Alg in the diet required to suppress the postprandial increase of blood glucose in rats [25].
We first examined the effect of Ca-Alg concentration on α-glucosidase activity, and observed no significant change compared to the control. On the other hand, the amount of glucose adsorbed on Ca-Alg increased with increasing initial glucose concentration until it reached saturation. The direct binding affinity of glucose for Ca-Alg was low, and the values of the permeation coefficient of glucose showed no significant change. Moreover, it has been reported that the addition of Alg (polysaccharides) increases the viscosity of starch suspension, and there is a positive correlation between apparent viscosity and the decrease of starch digestion [26]. We speculate that Ca-Alg interferes physically with contact between α-glucosidase and maltose by increasing the viscosity of the intestinal contents. It was our assumption that blood glucose suppression by Ca-Alg is the result of decreased efficiency in starch digestion due to the inhibition of α-glucosidase. This may be as a result of increased viscosity of the gastrointestinal contents. We next aimed to define the optimum amount and particle size of Ca-Alg in the diet for the suppression of postprandial blood glucose levels in rats [25]. A diet containing starch together with varying amounts and particle sizes of Ca-Alg was orally administered to rats randomized into five groups: starch with no Ca-Alg (control), or with Ca-Alg (3%; 270 mesh pass, 5%; 270 mesh pass, 5%; 150 mesh pass, or 5%; 80 mesh pass) (
Effect of starch diets containing Ca-Alg on blood glucose level in rats [
The in vivo study determined 5% of 270-mesh-pass Ca-Alg to be the most efficient combination of amount and particle size in the suppression of postprandial increases in blood glucose. Compared with 0% Ca-Alg, significant decreases were observed in both ΔCmax and ΔAUC, confirming a decrease in both postprandial peak glucose level and the full amount of glucose absorbed within 2 hours of ingestion. It seems likely that the magnitude of action would depend on the surface area of Alg.
Our results support the idea that Ca-Alg increases the viscosity of the gastrointestinal contents, depending upon the surface area of the administered gel. The gel is expected to interfere with the interaction between α-glucosidase and maltose, thereby suppressing the production of glucose, and preventing a sharp rise in blood glucose level. Various products have been reported to moderate glucose absorption; for example, indigestible dextrin has been confirmed to suppress the postprandial increase in blood glucose level by inhibiting α-glucosidase activity [28]. It seems reasonable to consider that Ca-Alg works similarly. Moreover, it was found that 5% of 270-mesh-pass Ca-Alg was the most effective combination of amount and particle size to suppress the postprandial increase of blood glucose (Figure 8).
A possible mechanism of blood glucose level-lowering effect of Ca-Alg [
To analyze the effect of Ca-Alg on the postprandial increase of blood glucose, a prospective, randomized, double-blind, 3-group, 3-phase crossover study was undertaken among healthy Japanese adult subjects [29]. Traditional Japanese udon noodles were selected, and blood glucose levels were measured after ingestion of Ca-Alg-free udon, and noodles containing 5 or 8% Ca-Alg. We also examined the effect of Ca-Alg on other chemical parameters in plasma or serum. Healthy male and female volunteers of 20 years of age or older were divided into three groups so that the average BMI values in the groups were similar. Each group ingested one of the three types of noodles containing 0 (control), 5 or 8% Ca-Alg (weight % to flour and modified starch). Blood was collected by fingertip puncture for blood glucose measurement prior to feeding and after ingestion. The blood glucose level was measured twice at each point using a simple blood glucose meter, and the average value was calculated. After eating the noodles, subjects were given a tasting questionnaire to evaluate “chewiness”, “thickness” and “favorability” of the noodles in a 5-point grading system (Figure 9).
Changes in blood glucose level (ΔC) after eating test noodles to volunteers [
Noodles containing 5 or 8% Ca-Alg caused a significant decrease in ΔCmax compared to control noodles. Moreover, ΔAUC also showed a significant decrease in both groups. No significant difference in the time of maximum blood glucose level (Tmax) was observed among the three groups. This is consistent with previous findings [31] and is similar to findings with α-glucosidase inhibitors, [32, 33] except miglitol [34]. These results indicate that Ca-Alg suppresses the postprandial increase in blood glucose and reduces the total absorption amount of glucose, but without delaying the absorption. Thus, our previous finding that 5% Ca-Alg had a blood glucose-suppressing effect in rats [25] was reproduced in humans.
As for blood biochemical parameters, no significant difference in the amount of Ca change at 30 min after noodle feeding (ΔCa30min) was found between the 5 and 8% Ca-Alg groups compared to the control, but ΔCa at 120 min (ΔCa120 min) showed a significant increase in both groups. In addition, ΔT-Cho30 min showed a slight tendency to decrease in both groups, and ΔT-Cho120 min was slightly decreased in the 8% Ca-Alg group. There was no significant change in other blood test values. We found that the blood Ca concentration at 120 min after eating 5 or 8% Ca-Alg-containing noodles remained within the normal range, 8.5–10.4 mg/dL, [35] but was significantly increased compared with the value in the control noodle group, suggesting that Ca derived from Ca-Alg was absorbed into the body.
The recommended amount of Ca intake in adults to help prevent diseases such as osteoporosis is 600–900 mg/day.[35] Since the amounts of Ca in noodles containing 8% Ca-Alg and 5% Ca-Alg would be 500 and 320 mg, respectively, about half of the recommended daily intake might be provided by these noodles. The upper limit of tolerable daily Ca intake for Japanese adults is 2500 mg, [35] so even if these noodles were eaten three times a day, the upper limit would not be reached. Thus, the likelihood of excessive Ca intake appears to be low.
Many substances are known to suppress glucose absorption; for example, indigestible dextrin has been shown to inhibit α-glucosidase. Our work showed that Ca-Alg also inhibits α-glucosidase activity [25], and its effect on blood glucose level was similar to or more potent than that of indigestible dextrin [36]. On the other hand, α-glucosidase inhibitors have side effects such as abdominal distention and flatus. Ingestion of noodles containing 8% Ca-Alg was expected to show an α-glucosidase-inhibitory effect equal to about 1/40th that of a single dose of acarbose [21]. Therefore, it is considered that the likelihood of side effects arising from α-glucosidase inhibition due to ingestion of noodles containing Ca-Alg is extremely low.
Our results raise the interesting possibility that the introduction of food ingredients containing Ca-Alg into the regular diet may be helpful in preventing lifestyle-related diseases, particularly diabetes and osteoporosis, without adversely affecting individual eating habits.
Alg, especially Ca-Alg, has a number of beneficial physiological effects. For example, we have shown that Ca-Alg increases excretion and reduces the absorption of toxic heavy metals such as Sr. and Cs in rats. Moreover, Ca-Alg decreases the blood Cho and TG levels, as well as reducing plasma levels of uric acid, allantoin and BUN levels in rats. Further, Ca-Alg moderated the postprandial increase of blood glucose level in rats and humans. Ca-Alg has been confirmed as safe for use as a food additive, and is superior to Na-Alg, because there is no risk of hypertension due to increased sodium intake. In addition, Ca-Alg may also have a preventive effect on osteoporosis. Ca-Alg is convenient to take, because it is effective in solid form, and it appears to be suitable for long-term use as an additive or functional food (Figure 10).
Revealed functions and future development of Ca-Alg.
Lifestyle-related diseases associated with high calorie intake and insufficient exercise have become a significant social problem [37, 38], and may lead to the development of cancer, heart disease and cerebrovascular disease, which are major causes of death [13, 14, 15, 16, 17, 23, 39, 40]. It will be interesting to examine further whether Ca-Alg may also offer potential benefits in relation to lifestyle-related diseases [36].
This work was supported by JSPS Grant-in-Aid for Challenging Exploratory Research (KAKENHI) Grant Number 25560062.
Fumiyoshi Kasahara is an employee of Kimica Corporation. The other authors have no potential conflicts of interest.
The treatment of joints using radioactive material began in the 1950s, more specifically in 1952, with chromic phosphate P32 [10]. It was initially aimed at joint involvement caused by rheumatoid arthritis and, to a lesser degree, pigmented villonodular synovitis, ankylosing spondylitis, collagenosis and psoriatic arthritis in the years that followed [24]. With the advent of longer follow-up studies, it has also benefitted rheumatic diseases and haemophilic arthropathy, which exhibit a similar sequence of events including repetitive intra-articular haemorrhages causing synovitis, joint pain, limited mobility and posterior muscular atrophy. Recurrent synovitis results in cartilage destruction, progressive loss of movement, joint deformities, bone damage and ultimately total ankylosis. The treatment procedure was originally denominated synovectomy (from the Greek ‘ectomía’ meaning ‘to cut out’) and later synoviorthesis (from the Greek word ‘orthesis’ meaning ‘restoration’) via radionuclides [8].
\nDifferent radioactive materials have been used to eradicate synovitis, some emitting only beta radiation and others beta and gamma radiation. Synovectomy in haemophilia using radioactive material began in 1971 [1]. Since then, a variety of materials have been used, including P32, colloidal 198Au, 186Re, 90Y, 165Dy, 166Ho, and 169Er. \nTable 1\n shows the characteristics of the materials used [1, 12, 16, 17, 18, 21, 28].
\nRadioisotopes | \nHalf-life (days) | \nMax. beta energy (MeV) | \nGamma energy (KeV) | \nPenetration (mm) | \nParticle size (μm) | \nLeakage (%) | \n|
---|---|---|---|---|---|---|---|
Max. | \nAv. | \n||||||
Colloidal 198Au | \n2.7 | \n0.96 | \n110 | \n3.6 | \n1.2 | \n0.02–0.04 | \n20–35 | \n
P32 (chromic phosphate) | \n14.0 | \n1.7 | \n– | \n7.9 | \n2.6 | \n0.05–0.1 | \n2–4 | \n
186Re (sulphide colloid) | \n3.75 | \n1.07 | \n140 | \n3.6 | \n1.2 | \n0.05–0.1 | \n2 | \n
Colloidal 90Y | \n2.7 | \n2.2 | \n– | \n10.8 | \n3.8 | \n1.5–3.5 | \n3 | \n
166Ho (FHMA) | \n1.2 | \n1.85 | \n81 | \n8.7 | \n2.2 | \n1.82–12 | \n1 | \n
165Dy (FHMA) | \n0.095 | \n1.3 | \n95 | \n5.6 | \n1.4 | \n0.8–12 | \n1 | \n
169Er (citrate) | \n9.4 | \n0.34 | \n– | \n1.0 | \n0.3 | \n0.1–10 | \n1 | \n
153Sm (HA) | \n1.95 | \n0.80 | \n100 | \n3.1 | \n0.8 | \n1–10 | \n0.1 | \n
Characteristics of the radioisotopes used in synovectomy.
FHMA = ferric hydroxide macroaggregates.
Irradiation occurs via the intra-articular retention of the radioactive material. However, it should be noted that the radioactive material is bound to larger particles, known as carriers, which undergo phagocytosis by the macrophages in the inflammatory process, favouring greater retention in the joint space. These macrophages migrate through the interstice of synovial cell layers, resulting in more homogeneous action by the ionising radiation. This behaviour was highlighted in autoradiographic studies [7], which more clearly indicate the location of samarium-153 particulate at different synovial tissue depths than other materials used, such as 186Re. This is also reported by Schneider et al. [23] (shown in \nFigure 1\n), in addition to direct irradiation by the intra-articular radionuclide. As such, average penetration is ascertained by the range of the β particle and maximum penetration by macrophage permeation into synovial cell layers.
\n(A) β-Emitting colloidal particles (yellow stars) phagocytised by inflamed hypertrophic synovial lining with proliferating synoviocytes (pink). The cartilage layer remains unaffected. (B) Subsequent cell damage and sclerosis of synovial membrane.
Another noteworthy aspect is that radionuclide leakage from the joint is inversely proportional to particle size. This is clearly evident in the last two columns of \nTable 1\n. The presence of gamma radiation allows synovectomy to be monitored over several days via scintigraphy.
\nHaemophilia is a congenital bleeding disorder linked to the X chromosome of the human genome, with the two most common types being haemophilia A, a lack of blood clotting factor VIII, and haemophilia B, caused by missing of defective factor IX. Joint bleeding associated with muscle bleeding represents 90% of bleeding episodes in haemophilia patients, while haemarthrosis alone accounts for 70–80% of these episodes. In 80% of cases, haemarthrosis occurs in the knees, elbows and ankles [22], producing inflammatory changes in the synovial membrane. Recurrence of this inflammation over time triggers a chain of events that lead to joint ankylosis, including the direct damage of blood on the articular cartilage [15].
\nIn cases of arthropathy mediated by reactive synovitis, synovectomy with radioactive material is an alternative to intra-articular injection of glucocorticoids and other chemical agents (osmic acid, collagenase, rifocin and thiotepa) or surgery. Furthermore, radiosynovectomy, introduced by Ahlberg in the 1970s, has been proposed as a first-line treatment option for haemophilic arthropathy [22, 23].
\n153-samarium was obtained in an IEA-R1 research reactor (IPEN-CNEN, São Paulo, Brazil) by neutron irradiation of 152Sm2O3 (99.4%) in the nitrate form, 152Sm(n,p)153Sm, for 30–36 h. The labelling process was performed with 40 mg of hydroxyapatite, using appropriately sized particles (20 μm), according to Barboza et al. [2]. Percentage bound activity or labelling efficiency was determined by centrifugation, measuring the activity of the precipitate (153Sm-HA) and supernatant (153Sm-free) using a dose calibrator, and was always >90%. Radiochemical purity was higher than 98%, measured using Whatman 3MM paper chromatography (from GE, Milwaukee, WI, USA) in 0.9% saline, remaining stable for 24 h. Particle size was determined by laser scattering and filtration in a filter system of known sizes (1–15 μm), with a mean of 10 μm (range: 3–12 μm). Microbiological tests for sterility and pyrogen were always negative in all samples.
\nParticipants were haemophilic patients with chronic synovitis, monitored at the Department of Haematology – Hospital de Apoio in the Federal District (DF), and the Orthopaedics and Nuclear Medicine Service of the Hospital de Base (DF), between 2002 and 2011.
\nPatients were assessed by clinical history and a physical examination, paying special attention to the compromised joint. Particular emphasis should be given to haematology tests in order to characterise the type and severity of haemophilia, as well as the absence of coagulation inhibition factors. Imaging (radiology) tests make it possible to determine the degree of arthropathy, with the Pettersson score being widely used. Three-phase whole-body scans are used to identify any other joints involved and more accurately characterise the synovial inflammatory process. Other procedures used for this purpose include ultrasound or magnetic resonance imaging (particularly for the knees).
\nInclusion criteria were the following: chronic synovitis when occurs repetitive effusions (minimum: once a month), pain on joint palpation and absence of other joint disease, like the rheumatologic or orthopaedic nature. Exclusion criteria were ruptured Baker’s cyst, major effusions, signs of acute synovitis or presence of an articular or periarticular infectious process.
\nSynovectomy of the radioactive material was made by an orthopaedist with previous use of the deficient clotting factor, applying topical anaesthesia in accordance with the asepsis and antisepsis performances used for invasive intra-articular orthopaedic procedures. The use of ultrasound to guide the punctures was not necessary, as these were assured by the aspiration of synovial fluid before administration of the radionuclide (\nFigure 2\n). Fixed doses of 5 mCi (185 MBq) or 20 mCi (740 MBq) of 153Sm-hydroxyapatite were used, with only one injection administered per patient. The maximum volume of radioactive material was 0.5 mL; material adhered to the puncture site was washed away with saline, at fractions of 0.5 mL, without exceeding the final volume of 1.5–2.0 mL.
\nInjection of the knee.
The reflux and homogeneity (or lack thereof) of the intra-articular material and its escape from the joint were monitored by a scintigraphic study in a gamma camera, with a wide field of vision detector and low-energy collimator. Imaging was made using a 128-pixel matrix and the spectrometer window was centred at 100 keV, using precocious, 1 and 2 h, and later times, 3–7 days, after 153Sm-HA injection. A summary of this protocol is shown in \nTable 2\n.
\n1 | \nUse a coagulation factor before the procedure; | \n
2 | \nLocal asepsis; | \n
3 | \nUse local anaesthetic; | \n
4 | \nJoint puncture using a 21G needle; | \n
5 | \nAspirate synovial fluid; | \n
6 | \nInject 5 mCi of 153Sm-HA into the intermediate joints and 20 mCi into the knees; | \n
7 | \nWash the puncture site with a total of 2.0 mL of saline without using corticosteroids; | \n
8 | \nCompression bandaging using crepe bandage; | \n
9 | \nMonitor the material used in the puncture; | \n
10 | \nFunctionally permissible joint mobility; | \n
11 | \nImmediate (1–2 hours after synovectomy) and later (3–7 days) scintigraphy image | \n
Protocol for synovectomy with 153Sm-hydroxyapatite.
Reactive synovitis may occur in the days following application of the radiopharmaceutical agent, which was treated using conservative measure such as joint rest, local application of ice and a non-steroid anti-inflammatory agent. The cases observed in our study were mild and occurred in 4–8% of joints.
\nRadionecrosis may occur if the material leaks from the administration route. This complication did not occur in the cases we treated because the material was only administered after correct injection and the puncture site was washed with saline to prevent leakage.
\nImmobilisation of the affected limb will ultimately result in thrombosis; however, this was prevented by the protocol used.
\nThere is no concern about possible carcinogenic effects of this procedure. Systemic irradiation can result from fluid leakage or the gamma component of 153Sm. Studies on chromosomal abnormalities in circulating lymphocytes related to samarium [19] have shown no definitive changes, but rather transient and reversible ones. It is important to note that this irradiation is smaller than in diagnosis by conventional bone scintigraphy or whole-body scanning with 67Ga. Considering the local effect at joint level, several studies with long follow-up times have shown no occurrence of tumours [14, 26, 27], indicating that this possibility has not yet been characterised.
\nThe first study was conducted to evaluate the efficiency of treatment with 153-samarium hydroxyapatite (153-Sm-HA) in haemophilic arthropathy. Thirty-one patients (30 males) between 8 and 34 years old (medium age = 20.6 years) were treated with a fixed intra-articular dose of 5 mCi (185 MBq) and divided into two groups: paediatric (13 patients aged up to 18 years, with a medium age of 12.7 years and arthropathy evolution of 7.8 years); and adults (18 patients over 18 years old, with an average age of 24 years and arthropathy evolution of 18.7 years). Clinical assessment before and 1 year after synoviorthesis used the following criteria: subjective (pain according to the visual analogue scale, joint inspection), objective (joint movement through flexion level, pain to palpation and leakage through joint circumference), reduced use of the coagulation factor, number of haemarthroses, and the occurrence of adverse effects. The results were classified as: 1, good (symptom remission of 70–100%); 2, moderate (symptom remission between 40 and 69%); and 3, poor (0–39% symptom remission). Seventy-eight joints were tested: 15 knees, 36 elbows, 24 ankles, 1 shoulder and 2 hips. Early (1–2 h) and late phase scintigraphic imaging (24–72 h) was made after synovectomy. No significant inter-group difference in synovectomy results was observed. The results obtained were good for 75% of elbows, 87.5% of ankles and 40% of knees; reduction in effusions and use of the coagulation factor were, respectively, 78% and 80% for elbows, 82% and 85% for ankles, and 30% and 35% for knees. Four cases of reactive synovitis were observed in the 78 joints tested. Scintigraphy showed homogeneous distribution of the material with no leakage. The introduction of 153Sm-HA in the treatment of the haemophilic arthropathy is effective for intermediate joints (elbows and ankles), but less so for knees. Moreover, this treatment offers excellent safety and is affordable [3].
\nThe penetration of beta energy from 153samarium (153Sm) (0.8 MeV) is not only suitable for synoviorthesis of intermediate joints, but can improve the radionecrosis effect using higher radioactivity levels. The next study assessed the efficacy of 5 mCi (185 MBq) and 20 mCi (740 MBq) of 153-Sm hydroxyapatite (153Sm-HA) in the knees of haemophilic patients. Thirty-one patients (36 knees, 30 males) were divided into two groups without corticosteroid co-injection: 1 – 14 patients (17 knees) treated with an intra-articular dose of 5 mCi of 153Sm-HA, medium age 23 years; 2 – 17 patients (19 knees), administering 20 mCi of 153Sm-HA, medium age 21.3 years. Evaluation before and 1 year after synoviorthesis used the following points: reduction in the number of effusions and use of the coagulation factor, and increment in joint mobility. The occurrence of side effects was also considered. Early and late-phase scintillations studies were made after synovectomy and no articular immobilisation was recommended. Reduction in effusions and use of the coagulation factor, respectively, were: group 1 – 31.3% and 25%; group 2 – 81.5% and 79%, with p < 0.001. No significant increment in knee mobility was observed in either group. Four cases of mild reactive synovitis were observed in each group. Scintigraphy showed homogenous distribution of the radioactive material with no leakage; the material was considered safe by its retention in the joint. A significant increment was observed in the synoviorthesis of haemophilic knees with 20 mCi of 153Sm-HA; the lower penetration of its beta radiation was offset by the improved radiobiological effect when higher radioactivity is used [4].
\nAnother study compared the use of 20 mCi (740 MBq) of 153Sm and 5 mCi (185 MBq) of 90Y, both labelling hydroxyapatite (HA), for knee synoviorthesis in haemophilic patients, 1 year after the procedure. Thirty-three men (36 knees) were studied, divided into two groups: a – injection of 740 MBq of 153Sm-HA: 20 knees of 18 patients, with an average age of 21.4 ± 13.3 years (range: 7–56 years) and medium Pettersson score of 5.3; b – injection of 185 MBq of 90Y-HA: 16 knees of 15 patients, with an average age of 26.3 ± 10.3 (range: 7–51 years) and medium Pettersson score of 6.3. Episodes of haemarthrosis, use of clotting factors and pain intensity were evaluated before and after treatment, as well as improved joint mobility. The occurrence of side effects in the treatment was also considered. The chi-squared, Wilcoxon and Mann–Whitney tests were applied, with a significance level of p ≤ 0.05. The occurrence of effusions decreased by 65.7% with the use of 153Sm-HA and 82.6% for 90Y-HA, without statistical significance between the groups (p = 0.632); pain reduction was 42.5% in group a and 30.7% in group b, again without statistical significance (p = 0.637). Increment in joint mobility was not significative for either group. Two cases of mild reactive synovitis were observed in group a and one in group b, which had resolution without medical intervention. Although the beta energy from 90Y is the more appropriate for knee synoviorthesis, the higher radioactivity levels of 153Sm is an alternative in locations that only produce this material [5].
\nThis study aimed to evaluate synovectomy with 153Sm-hydroxyapatite (153Sm-HA) in synovitis of the elbows and ankles of haemophilic patients. Synovectomy was performed using 185 MBq of 153Sm-HA in 166 joints (63 ankles and 84 elbows) of 82 haemophilic patients (average age 24.4 years) with follow-up of 12 and 42 months. Arthropathy was characterised by recurrent joint bleeding. Episodes of haemarthrosis, use of clotting factors and pain intensity were evaluated before and after treatment. Scintigraphic analyses and adverse effects were also considered. Statistics used p ≤ 0.05. The results indicated: (a) reduction in haemarthrosis was 78% and 68%, in elbows and 82% and 72% in ankles; (b) use of clotting factors was 80% and 70% for elbows, and 85% and 75% for ankles; (c) pain intensity was 37% and 34% in elbows, and 61% and 57% in ankles, after 12 and 42 months, respectively. Among the 166 joints studied, three cases of mild reactive synovitis were observed in ankles and four in elbows, with no leakage in any of the cases. In conclusion, the use of 153Sm-HA in elbows and ankles was effective, very safe, minimally invasive and the results showed consistency at follow-up [6].
\nAnother interesting aspect to consider is treatment repetition. We recommend this be done after 1 year, but a minimum interval of 6 months is permitted.
\nThe radioactive material (153Sm) was aggregated with hydroxyapatite particles to ensure longer intra-articular retention without arterial-venous or peri-articular lymphatic leakage. When the two are separated, the advantage of the compound is that the carrier (hydroxyapatite) enters the body’s metabolism because it is part of the bone matrix.
\nNo escape (lymphatic or vascular) was detected with 153-samarium because when it separates from the carrier (hydroxyapatite), it forms insoluble compounds with the synovial fluid that precipitate in the articulation; this permanence was confirmed by other previous studies [20] and by our controls (see \nFigure 3\n).
\nKnee scintigraphy showing good joint distribution and no leakage.
Scintigraphic images obtained after early and late-phase injection showed appropriate intra-articular distribution, as well as the absence of leakage to regional lymph nodes or other organs, or urinary elimination. The ability to obtain good-quality scintigraphic images is an advantage of 153Sm since gamma emission occurs in the energy amplitude of 100 keV. Another possible advantage is the mild reactive synovitis observed in all the studies, resolved without invasive medical intervention, possibly due to low beta energy penetration.
\nThese studies are among the few that evaluate only the therapeutic effect of intra-articular radioactive material, since it is often administered in conjunction with corticosteroids. This creates bias in result analysis because corticosteroids are also used for the same purpose in the treatment of haemophilic arthropathy [11]. This combination has been called into question [13] and is one of the reasons why we chose not to use it when beginning treatment [3], in addition to the lack of information in the literature characterising the nature of its effect as competitive, additive or synergistic.
\nThe reduction in haemarthrosis for ankles (82%), elbows (78%) and knees (65.7%) was similar to values recorded in other studies of haemophilic patients with different types of radioactive material. A German revision pointed nine studies between 1982 and 1991 with good and excellent results for radiosynovectomy in 60–80% of the haemophilic arthropathy [9]. The findings presented in our studies also corroborate those summarised by Siegel et al. [25] regarding the benefits of radiosynoviorthesis, with an approximate 75% decrease in effusions, few adverse effects and better quality of life in 75% of the cases. This can be extended to shoulders and hips, which exhibited similar results to intermediate joints. Finally, it can be concluded that 153samarium labelled with hydroxyapatite is a useful tool in the treatment of chronic synovitis in haemophilic patients.
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',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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He is the author of several scientific articles, book chapters, and books.",institutionString:"University of Hassan II Casablanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Hassan II Casablanca",institutionURL:null,country:{name:"Morocco"}}},equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7060",title:"Gingival Disease",subtitle:"A Professional Approach for Treatment and Prevention",coverURL:"https://cdn.intechopen.com/books/images_new/7060.jpg",slug:"gingival-disease-a-professional-approach-for-treatment-and-prevention",publishedDate:"October 23rd 2019",editedByType:"Edited by",bookSignature:"Alaa Eddin Omar Al Ostwani",hash:"b81d39988cba3a3cf746c1616912cf41",volumeInSeries:4,fullTitle:"Gingival Disease - A Professional Approach for Treatment and Prevention",editors:[{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"6668",title:"Dental Caries",subtitle:"Diagnosis, Prevention and Management",coverURL:"https://cdn.intechopen.com/books/images_new/6668.jpg",slug:"dental-caries-diagnosis-prevention-and-management",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Zühre Akarslan",hash:"b0f7667770a391f772726c3013c1b9ba",volumeInSeries:1,fullTitle:"Dental Caries - Diagnosis, Prevention and Management",editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Prosthodontics and Implant Dentistry",value:2,count:3},{group:"subseries",caption:"Oral Health",value:1,count:6}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2020",value:2020,count:2},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:229,paginationItems:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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