Iris Publishers-Open access Journal of Civil & Structural Engineering | Opportunities to Increase the Reliability of Existing Retaining Walls

 

Authored by Sokolov NS*,

Abstract

The problem of increasing the bearing capacity of foundations is always an urgent problem in modern geotechnical construction. With additional increased external loads on existing retaining structures, the use of traditional technologies to ensure their stability is not always justified. Often there is an urgent need to use non-standard methods of strengthening the bases. There are frequent cases of using existing retaining reinforced concrete structures for new additional loads from newly built objects. In such cases, the use of EDT bored piles allows solving complex geotechnical problems associated with the possible strengthening of overloaded foundations.

Keywords: Geotechnical construction; EDT (Electric discharge technology); EDT bored pile; EDT ground anchors

Introduction

The construction of industrial and civil facilities in cramped conditions requires a specific approach related to ensuring the safety and reliable operation of the surrounding buildings. To solve geotechnical problems related to this problem, the electric discharge technology of EDT piles is one of the most popular [1- 10]. One of the cases of geotechnical construction for a multi-Storey public building in the city of Nizhny Novgorod is considered. The project for a ten-story hotel building provided for the installation of ERT bored injection piles. The construction of the facility was carried out in difficult engineering and geological conditions in the old bed of the Volga River. The engineering-geological section in this area is represented by the following engineering-geological elements (EGE) (from top to bottom):

Table 1:

The construction site is characterized by a high level of underground (non-pressure) water. The construction of the facility began 5 years before the start of the main construction with the erection of a pit fence (9.0 m deep) from two rows of bored piles with a diameter of 450.0 mm with a step of 1.0 m (see Figures 1 and 3). The retaining wall of the excavation was built along the adjoining streets. Directly adjacent to the foundation pit is a 10-storey largepanel residential building erected on driven piles. The disadvantage of the constructed fence was the absence of a monolithic reinforced concrete strapping belt along the top of the injection piles. This flaw came to light only when excavating the pit. A row of fence piles from the side of the adjoining building leaned towards the excavation (the maximum horizontal movement reached 85.0 mm). As a result of this situation, deformation cracks appeared on the outer walls of the residential building. At the same time, the installed gypsum beacons broke and continued to tear, thus proving the ongoing deformation of both the wall itself and the residential building. At the same time, all walls on the other sides of the pit are also deformed. Urgently created in connection with the pre-accident situation, the emergency commission instructed the head design organization to urgently develop emergency response measures to stabilize the deformations of both the erected retaining wall and the adjoining existing building. As such measures, a scheme was developed to reinforce the retaining wall in the form of spacer structures made of steel pipes with a diameter of 1000.0 mm (see item 5 of Figures 1 and 3), located at two levels in mutually perpendicular directions. These measures made it possible to stabilize the critical situation that had arisen. The gypsum beacons on the residential building stopped tearing, the horizontal movements of the retaining wall were suspended. At the same time, geotechnical monitoring continued. With a design excavation depth of 9.0 m, the spacers were placed at a depth of 4.5–6.5 m. In this frozen state, the object was more than five years.

In connection with the appearance of an investor, it was decided to erect a completely different building from the one previously planned for construction at this construction site - a ten-story public facility. At the same time, the designers had to fit into the dimensions of the site in the inner contour of the completed fence made of bored piles (pos. 1, Figures 1 and 3), and also take into account the existing schemes for reinforcing retaining walls using spacer structures made of steel pipes (see pos. 3 on Figures 1 and 3).
The construction of buried reinforced concrete foundation structures faced a special technical difficulty for builders due to the presence of often located horizontally mounted pipes. The ideal task is a) dismantling of steel pipes and b) replacement with more advanced geotechnical reinforcement technology. At the same time, the retaining wall of the fence at the junction with the existing tenstory residential building still remains the weakest link. By a joint decision, it was decided to arrange buttresses (see pos. 3 in Figures 1 and 3), supporting the excavation fence near the residential building through a monolithic reinforced concrete structure (see pos. 2 in Figures 1 and 3), arranged between the existing expansion constructions. The base for monolithic reinforced concrete grillages (see pos. 4 Figures 1 and 4) of the buttresses was proposed to use ERT bored injection piles (pos. 2 Figure 2) in the form of separate bushes for a monolithic reinforced concrete grillage, manufactured using electric discharge technology (ERT technology). The need to use EDT piles with a diameter of 0.35 m and a length of 12.0 to 19.0 m, depending on engineering and geological conditions in one or another part of the construction site, is due to the purpose of ensuring the stability of the buttress against shear from horizontal forces. It was decided to arrange buttresses with grippers: 1. Finished buttress with a set of design strength of all its elements; 2. Dismantling of one steel pipe. In this sequence, the struts are replaced with buttresses. In connection with the fact that the gap between the pipes was three meters, it was decided to use the drilling rig “Berkut” for the installation of EDT piles (see item 1, Figure 2). To enter it into the annular space, the builders covered it with sand. EDT piles had to be installed in very difficult conditions between the pipes, and the removal of soil from the pit was carried out only manually. It should be emphasized that monolithic reinforced concrete buttresses were the supporting building structures for the above-ground load-bearing walls.
Thus, in order to ensure the safe operation of the retaining wall during the construction of the zero cycle, as well as to create conditions for the dismantling of steel pipes of spacer structures, an algorithm for constructing buttresses was developed, the positions of which are given below:

Table 2:

The work on the implementation of the above algorithm made it possible to gradually dismantle the spacer pipes. No further deformations of the retaining wall and residential building were found. The installation of ERT bored piles for buttress foundations, buttresses, as well as the grillages themselves, were carried out by one contractor. At the same time, horizontal movements of the retaining wall and deformations of the sedimentary marks of the residential building were monitored daily, due to which there were no violations in the technological chain (algorithm) at this site: “drilling - concreting - electro-hydraulic treatment of the walls and heel of the well - installation of reinforcement cages”. Mandatory stages confirming the compliance with the project of the designed EDT piles for the foundations of the buttresses:

Conclusion

1. The implementation of geotechnical work on the implementation of the above algorithm made it possible to gradually dismantle the spacer pipes. No further deformations of the retaining wall and multi-Storey residential building were found.
2. Long-term observations of the technical condition of a multi-storey large-panel residential building make it possible to conclude that the decision made on the installation of monolithic reinforced concrete buttresses is technically correct.

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Iris Publishers-Open access Journal of Biology & Life Sciences | The Discovery of Human Tropism

 

Authored by James T Struck*,

Introduction

We all know from our botany classes that plants exhibit tropism. A plant will turn towards the Sun or magnetic fields will affect the growth of a plant. There is some evidence that tropism happens in humans as well.

Discussion

The Dutch and Norwegians are among the tallest group of homo sapiens. (Article on google about tallest humans) 1. Norway gets the most sunlight with never ending sunlight for about 76 days [1]. Many of the tallest nations are Montenegro, Germany, and countries like Slovenia and Croatia. A possible explanation for that increased height is more sunlight in Europe.

“Does Norway Get a Lot of Sun?

Norway. Norway, situated in the Arctic Circle, is called the Land of the Midnight Sun, where from May to late July, the sun actually never sets. This means that for around a period of 76 days, the sun never goes down. Aug 26, 2022” [2].

The top 5 groups of human nations in Bill Bostock’s list are Netherlands, Latvia, Estonia, Denmark, Czech Republic.

Conclusion

We conclude there exists possible tropism or growth towards the sun among humans. Something else may be increasing growth and height among Europeans, but that topic is open to discussion like better diet and nutrition.

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Iris Publishers-Open access Journal of Complementary & Alternative Medicine | The Need for a Deeper Notion of Holism in Complementary and Alternative Medicine

 

Authored by Hans A Baer*,

Short Communication

I am writing this opinion piece from my perspective as a critical health and ecological anthropologist who has grappled since around 1980 with various CAM systems, particularly osteopathy, chiropractic, naturopathy, Chinese medicine, in the US, UK, and Australia, and more recently since 2005 with anthropogenic climate change. Both CAM and critical health anthropology are committed to the notion of holistic health and perhaps even planetary health, albeit in different ways. In reality, CAM is an amorphous category created by progressive biomedical physicians responding to the growing popularity of a wide array of alternative or heterodox health medical systems which found common cause under the umbrella of the holistic health movement in the 1970s [1]. Integrative medicine also arose as a biomedical construction to supposedly blend the best elements of biomedicine and CAM and also adopted the notion of holism, but some would argue to co-opt various CAM systems [2,3]. What is desperately needed is an examination of how the various CAM systems define holistic health and health care. Nevertheless, my sense in having examined various CAM systems and medical pluralism for four decades is that CAM practitioners tend to view holism in terms of making mind-body-spirit connections, but often tend to either neglect or downplay the role of political, economic, and social structural, and environmental factors in disease etiology. Needless to say, there are exceptions to his observations. For example, the School of Natural and Complementary Medicine at Southern Cross University in Australia developed a Basic Model of (W)holistic Medicine in 1999 which recognises six elements in whole-person care: (1) physical, (2) mental, (3), spiritual, (4) family, (5) community, and (6) environment [4].

Critical health anthropology (CHA), formerly referred to as critical medical anthropology (CHA), understands health issues within the context of political and economic forces [5]. These forces are institutional, national, and global in scale. They pattern human relationships, shape social behaviours, condition collective experiences, reorder local ecologies, and situated cultural meanings. The emergence of CHA reflects both the turn toward political-economic and political-ecological approaches in anthropology in general beginning in the 1960s, a period of social ferment around the globe, as well as an effort to engage with and extend the larger political economy of health approach. CHA seeks to provide a perspective and set of concepts for analysing macrointermediate- micro or global-national-local connections. At the macro level are the power relations of the capitalist world system and its associated corporate and state sectors coupled with plural medical systems; at the intermediate level are health institutions such as hospitals and clinics; and at the micro level are the healerpatient relationship and the patient experience.

CHA asserts that health ultimately must take precedence over health care, because the latter often comes into play once disease or illness has occurred. Critical health anthropologists define health in terms of access to and control over the basic material and nonmaterial resources that sustain and promote life at a high level of well-being. In essence, health is an elastic concept that must be considered within a larger sociocultural context. It is the product of a dialectical interaction of natural, political-economic, and sociocultural forces.

Disease or illness also varies from society to society, in some because of climatic and geographic conditions, but in large part because of the ways resources and productive activities are organised. It is not just the straightforward result of a pathogen, physiological, or anatomical disturbance as argued by biomedicine. Rather it is a result of a variety of social structural conditions all of which are ultimately roots in the capitalist world system with its emphasis on profit-making, continual economic growth, and a treadmill of production and construction that place tremendous pressure on the planetary ecosystem. Thus, disease and illness can result from malnutrition, social stratification, economic insecurity, alienation in the workplace, occupational risks, industrial and motor vehicle pollution, inferior housing, poor sanitation, the stress of everyday life, and environmental and climatic degradation.

CHA argues that the achievement of health with authentically and pluralistic health care requires the transcendence of global capitalism. It argues for the construction of a global democratic ecosocialist order that combines the principles of public ownership of the means of production, social equality, centralism, decentralism, representative and participatory democracy, environmental sustainability, and a safe climate [6]. CHA contends that progressive people, including health care workers, need to come to terms with both the achievements of post-revolutionary societies and to reconceptualize the notion of socialism. It recognizes that we live on an ecologically fragile planet with limited resources that must be shared and sustained and renewed for future generations. Ultimately, the shift to democratic eco-socialism would have to be part and parcel of global process that no one can fully envision.

Given the small size of complementary and alternative medicine in the various countries where it exists, CAM practitioners need to join forces with progressive biomedical practitioners as part of a larger process of advancing an authentically holistic health paradigm that recognizes that health and disease are ultimately embedded in political, economic, social structural, and ecological processes. Howard Waitzkin, a critical sociologist and progressive biomedical physician, argues: “Because of the powerful economic and political interests that dominate the health care system, the alternative movement cannot succeed unless it connects itself to broader political activism as well” [7]. In the US context, the creation of a universal health care system could pave the way to provide CAM therapies to working-class and poor people. In the case of countries with nationalized health care, such as Canada, the UK, Australia, and New Zealand, CAM therapies could be incorporated into an integrative health system in which biomedical and CAM practitioners work as co-equals in a collaborative relationship that blends an emphasis on both preventive and curative care. The larger struggle, however, is the creation of nationalized and holistic integrative health care systems in all countries as part of the struggle for a healthy planet.

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Iris Publishers-Open access Journal of Textile Science & Fashion Technology | Study the Effect of BTCA Crosslinking Agent on Crease Recovery Angle and Washing Shrinkage Properties of Bleached and Dyed with Bi- and Tri- Functional Reactive Dyed Woven Cotton Fabric

 

Authored by Yimer Hassen*,

Abstract

Easy care finishing of textile materials is one of textile chemical finishing processes to make cellulosic textile materials crease free and dimensionally stable in its service life or during wear. There are different types of crosslinking agents for easy care finishing of cotton fabric. Among these, 1,2,3,4-buthanetetracarboxylic acid is the most effective and formaldehyde free crosslinking agent. On the other hand, woven cotton fabric treated with reactive dyes to give color to textiles. It reacts with fiber in presence of alkali and forms covalent bond with hydroxyl group of cellulosic fibers. In this study, therefore, investigates the effect of covalent bond formation between reactive dyes and cellulose fiber on crease angle recovery and washing shrinkage percentage properties after treated with BTCA crosslinking agent. Initially, cotton fabric was treated with reactive dyes using cold-pad-batch method and followed by easy care finishing for both bleached and dyed fabric using pad-dry-cure method. The application of Bi- and Tri- functional reactive dyes reduces the total crease recovery angle and Tri- functional reactive dye improves the washing shrinkage percentage properties of cotton fabric.

Keywords:Cotton fiber; Reactive dyeing; Crosslinking agent; Crease recovery angle; Washing shrinkage; Strength

Introduction

Finishing is generally the last stage of modern textile production. Its goal is to convert the bleached, dyed or printed cellulosic or other fabrics by mechanical and chemical treatment into a suitable state for sale and making-up. Easy care finishing also known as resin finishing, wash-and-wear finishing or durable finishes is the one among different techniques of chemical finishing of textiles. This method of finishing helps cellulosic fibers to maintain a stiff, just ironed or wrinkle free appearance through the lifetime of the article despite various disadvantages such as strength losses, shade changes and reduced whiteness [1,2]. The primary cause of the shrinkage and crease formation of cellulosic fibers is the fact that these fibers can readily absorb moisture. This absorbed moisture facilitates internal polymer chain movements in the amorphous fiber areas by lubrication. It disrupts the internal hydrogen bonding between these polymer chains. When a moisture laden cellulosic fiber is stressed, the internal polymer chains of the amorphous areas are free to move to relieve that stress. Then, hydrogen bonds can reform between the polymer chains in their shifted positions, in effect, locking in the new configuration. With no restoring forces available, a newly formed shrinkage or crease will remain until additional processes (for example ironing) apply adequate moisture and mechanical forces during to overcome the internal forces [3,4]. The swelling of cellulosic fibers by moisture can be reduced by the application of self-crosslinking agents and products which reacts with the cellulose molecules. In recent days, crosslinking agents from very low formaldehyde to zero formaldehyde release have been developing. N,N’-Dimethylol-4,5-dihydroxyethylene urea (DMDHEU), N,N’-Dimethyl- 4,5-dihydroxyethylene urea (DMeDHEU) and 1,2,3,4-Butanetetracarboxylic acid (BTCA) are some of the crosslinking agents used recently [3,5-10]. On the other hands, dyeing is the application of color to a textile material. Reactive dyes are one of among different groups of dyes depending on the application methods. Reactive dyes are a highly successful class of modern synthetic dyes owing to their wide shade gamut, their flexibility in application, and the excellent fastness properties they offer when dyed on cotton and other textiles. Reactive dyes may be loosely defined as chromophores that contain pendant groups capable of forming covalent bonds with nucleophilic sites in fibrous substrates during the fixation steps [10]. Bi-functional and Trifunctional reactive dyes which are characterized by the presence of two or three reactive groups were used in this study. Both of the dyes have been applied at room temperature in alkaline condition followed by fixation and rinsing process. The main purpose of this research work is to find out the effect of reactive dyeing on total crease recovery angle, washing shrinkage percentage and other important and related textile properties of cotton fabric in the application of crosslinking agents [5,11,12]. In this study we have focus to evaluate the influences of reactive dyes on CRA and washing shrinkage percentages of the fabric. In addition, we have seen its effect on different other useful textile properties, such as, strength, flexural rigidity, abrasion loss and air permeability of woven cotton fabric [1,12,13]. Furthermore, most finishes are applied to fabrics such as woven, knitwear or nonwovens. It is also possible to apply finishes to other forms of textile materials, such as fiber, yarn or garment. Therefore, this research work results could be the foundation to be applied on cotton fiber and yarn stages to study or investigate the differences and to optimize processes.

Materials and Methods

Fabric

Mercerized full bleached cotton fabric with the following specification was used: end/cm, 38; picks/cm, 30; and weight, 130 g/m2

Chemicals

1,2,3,4-buthanetetracarboxylic acid crosslinking agent , Trifunctional orange reactive dyestuff , C.I. Reactive Black 5 reactive dyestuff, sodium carbonate and Sodium hydroxide solution 33% alkaline agent were used in treatments and after washing processes.

Methods

In this investigation, initially, woven cotton fabric has been treated with Bi- and Tri- functional reactive dyes in alkaline condition. The dyeing has been done in a cold-pad-batch method. The dyes and the alkaline agents are prepared separately to avoid hydrolysis of the dyes. All were mixed up only just before padding. It stayed for 24 hours at room temperature for fixation followed by rinsing and soaping. Then, Bleached and dyed sample were treated with 100g /l of BTCA and cured at 130 °C for 3 min using pad-dry-cure method. Samples had 90% average pick-up values. In this test, CRA (Back and face or warp and weft directions), washing shrinkage (in both direction) and other important textile properties has been measured. In each test five samples have been measured. Abrasion resistance tester, FX-33 00 TEXTEST air Permeability tester, washing shrinkage standard ruler, washing laundry, Stiffness measuring inclined plane, weighing balance, TruBurst, water capillary rise, CRA, oven dryer, curing machine and Padder were the machines or instruments used in treatment and testing of the fabrics.

Results and Discussion

Total crease recovery angle

Crease resistance of fabric is the ability of the fabric to prevent the formation of wrinkles or creases on the surface of the fabric during various uses or process. The crease resistance of the fabric is expressed in the term of crease recovery angle. The total crease recovery angle is the sum of warp and weft crease recovery angles. According to ISO 2313-1972(E) method, twenty specimens have been measured from both warp and weft way of the fabric. Each sample has 15 mm by 40 mm size. It has been loaded with 1kg for five minutes and five more minutes for recovery after unloading. The measurement has been done for both faces of the fabrics. All the results are in nearest degrees. As shown in Figure 1 and Table 1, the total crease recovery angle increases as the concentration of BTCA increases for bleached fabric and decreases for reactive dyed samples [1,14-16].

Table 1:Total crease recovery angle of woven cotton fabrics treated with BTCA and reactive dyes.

Washing shrinkage percentage

Measuring Washing shrinkage percentage is used as a factor that determines the change in length and width of the fabric after washing. Shrinkage has great significance because any expansion or shrinkage can cause deformation of the product, which could be a severe concern for the end-user. In this test, according to ISO 6330:2012-08, washing agent (40 g) and Sodium carbonate (20 g) have been used for 2 kg of the woven cotton fabric. In addition, washing was performed under 60 °C for 75 min. of washing time. As shown in Figure 2 and Table 2, nearly no washing shrinkage has been seen in Tri-functional reactive dyeing. On the other hand, washing shrinkage and stretch has been increased in Bi-functional reactive dyeing as compared to cotton fabric treated with only BTCA [1,14].

Table 2:Average washing shrinkage percentage of woven cotton fabric fabrics treated with BTCA and reactive dyes.

Air permeability

Air permeability is the rate of air flow passing perpendicular through a known area under a prescribed air pressure differential between the two surfaces of a material. It is a measure of how well a fabric allows the passage of air through it. It is assumed to be that the possible formation of 3D structure of crosslinking agent formation than reacting with the cellulosic material will reduce the air permeability properties of cotton fabric. In this test, according to DIN EN ISO 9237 method we have used air permeability testing machine with a diameter of 20cm2 and pressure of 100Pa. The measurements are in mm/s. As shown in Figure 3 and Table 3, the air permeability of woven fabric is higher when the fabric treated with only BTCA whereas it is reduced in both reactive dyeing [14] .

Table 3:The average air permeability of woven cotton fabric fabrics treated with BTCA and reactive dyes.

Bursting strength

Bursting strength is the force that must be exerted perpendicularly to the fabric surface to break off fabric. Strength of the fabric is an important property that decides and influences all other performance properties of the woven or knitted fabrics. Consideration of the strength of the fabric is very essential while selecting the appropriate fabric for the intended garment or end uses. According to ISO 13938-1:1999(E) method we have taken five tests diagonally for each sample to represent all the threads in different parts of the fabric with 600kpa clamping at pressure rate of 13 and 10 in kpa for Bi- and Tri- functional reactive dyes respectively. TruBurst2 instrument was used for measuring the strength of the samples. All the measurement results are in KPa. As shown in Figure 4 and Table 4, the strength of the material was improved in Bi-functional and reduced in Tri-functional reactive dyes [17].

Table 4:Bursting strength of cotton fabrics treated with BTCA and reactive dyes.

Abrasion resistance

Abrasion resistance is the ability of a fabric to resist surface wear. Abrasion is the physical destruction of fibers, yarns, and fabrics resulting from the rubbing of a textile surface over another surface. In this test, 11cm by 11cm sample size cotton fabric has been used. The Abrasion instrument has been set to 3000 rpm for 30 s for each sample. The weight differences have been measured in grams for each. As shown in Figure 5 and Table 5, the abrasion loss increased for fabric treated with BTCA as compared to untreated cotton fabric. And, Tri- functional reactive dye has higher abrasion loss as compared to Bi-functional dyed fabric. But, in general, dyed fabric with Bi- and Tri-functional reactive dyes have less abrasion loss as compared to bleached and fabric treated with BTCA [15,16,18].

Table 5:The average abrasion loss of cotton fabric in grams fabrics treated with BTCA and reactive dyes.

Flexural rigidity

Flexural rigidity is a measure of stiffness associated with handle. Fabric stiffness and handling is an important decision factor for the end users. The degree of fabric stiffness is related to its properties such as fiber material, yarn, fabric structure and type and method of chemical finish. Three-dimensional crosslinking structure against to the reaction with cellulose determines the level of fabric stiffness properties. 20cm by 4cm specimen size has been taken from both ways of the woven fabric. Using DIN 53362, five replications have been taken from each test specimen. Since the finish is generally associated with an increase the weight of the sample, the flexural rigidity must be calculated independent of the sample weight. As shown in Figure 6 and Table 6, the flexural rigidity of woven cotton fabric increases treated with Bi*functional reactive dye and BTCA has higher flexural rigidity in warp than other treatments

Table 6:Average flexural rigidity of cotton fabric in mg*cm treated with reactive dyes and BTCA.

Conclusions

Cellulose fiber especially cotton is the most important kind of fiber because of their numerous advantages. However, wrinkling after washing is one of the main disadvantages. BTCA anti-swelling or crosslinking agent is one of the most formaldehyde free finishing agents for wrinkling free treatment. It disrupts new hydrogen bond configuration by forming strong covalent bond with cotton fiber. Easy care finishing affects the fabric properties because of the crosslinking between cellulose molecules and chemical used in the treatment process. The reactive dye constitutes the most commonly used class for dyeing cellulose fiber. The dye contains a reacting group and this reactive group form covalent bond with the fiber and as integral part of the fiber. Both anti-swelling and reactive dye form covalent bond with cotton fiber. In this investigation we have found that reactive dyeing before anti-swelling treatment reduce CRA, abrasion loss and air permeability of cotton fabric. Bi-functional reactive dyeing improves the strength, resulted shrinkage in warp and stretch in weft direction, and increased the stiffness of the fabric. On the other hand, Tri-functional reactive dye reduced strength and stiffness, and nearly no washing shrinkage on both ways of the fabric. Furthermore, it needs to consider the order of treatment and IR analysis for additional information in research work.

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Iris Publishers-Open access Journal of Neurology & Neuroscience | Immunological Aspects Related to the Pathophysiology of Multiple Sclerosis and the Possible Checkpoints for Target Therapy: An Integrative Literature Review

 

Authored by Douglas Reis Abdalla*,

Introduction

Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS), with an autoimmune inflammatory mechanism, affecting in the form of characteristic lesions called “plaques”, the white substance of the brain stem, cerebellum, spinal cord and optic nerve [1,2]. The tissue damage in MS results from a complex and dynamic interaction between the immune system, glial cells and neurons. However, this autoimmune inflammatory aggression, characterized by a lymphocytic infiltrate that crosses the blood-brain barrier, over the myelin sheath of the CNS axons, leads to the loss of trophic factors produced by this protective layer, promoting a permanent axonal degeneration, resulting in a series of motor and sensory signs and symptoms [3,4]. Worldwide, it affects about 2.5 million people and within that amount, 35 thousand are Brazilian [5]. Among those affected, most of them are young adults between 20 and 40 years of age. In Europe and North America, MS is considered a highly prevalent disease, since for every 100,000 inhabitants, 60 to 200 sick individuals are found [6]. This reality does not correspond to South America, which has a rate of less than 5 cases per 100,000 inhabitants, that is a low prevalence [7].

In Brazil, the incidence is about 5-30 cases per 100,000 inhabitants, but varies according to the region [6]. In addition, there are studies that show that the disease predominates in white women with the outbreak-remissive form in the national and international context. However, in a study in Rio de Janeiro, 31.8% of black patients were found. In general, MS is a rare disease among blacks, it is believed that the largest number of blacks in Brazilian studies is due to a change in genetic susceptibility as less favored socioeconomic conditions and to the racial mixture present in the Brazilian people [8].

Regarding the etiology of MS, this remains unknown, however, it is believed to be caused by immune dysregulation triggered by genetic and environmental factors [9]. Although MS is not an inherited disease, there is a strong genetic component in its etiology, as evidenced by the grouping of MS cases in families. The risk of MS among first-degree relatives with MS is 10 to 50 times higher than the general population (absolute risk 2 to 5%); the agreement rate in monigotic twins is about one third [10,11]. Linkage analysis studies have revealed several genetic sites as risk factors, with the HLA DR15/DQ6 allele being the main histocompatibility complex (MHC) the strongest [12,13]. Alleles of the interleukin-2 receptor alpha gene (IL2RA) and the interleukin-7 receptor alpha gene (IL7RA) have also been identified as inheritable risk factors [13,14]. However, most of the genetic factors underlying susceptibility have yet to be defined. In addition, in the autoimmune hypothesis, the demyelization process begins with activation of peripheral CD4 + T cells with reactivity to myelin. However, in this hypothesis, unlike the viral infectious hypothesis, the cause of activation is unknown. Activated CD4 + T cells cross the blood-brain barrier, genetically altered, towards the Central Nervous System, aided by an increase in the number of adhesion molecule receptors expressed by endothelial cells [15]. According to Dos Santos et al. (2005) [16], myelin autoantigens, especially Basic Myelin Protein and Myelodendritic Glycoprotein, are presented by macrophages to these CD4 + T cells, triggering a cascade that releases inflammatory mediators and culminates in the injury, or even destruction, the myelin sheath. In addition to the action of T cells, we observed the participation of B cells in the infiltrate and the action of antibodies on the surface of the myelin that acts in the demyelination process, in addition to molecules of the Complement System [17]. Currently, early treatment of MS is expected to be related to preventing the patient’s long-term disability. These treatments can be immunosuppressive or immunomodulatory, which implies that it is necessary to control inflammation and, consequently, disease activity. The closest that has ever come to a potential cure has been immune reconstitution therapies [18]. A concept in treatment has recently been developed that suggests that clinical recurrences of the disease are a small part of the disease, which is “no evidence of disease activity” or NEDA. This fact arose from the perception that scholars had about continuous inflammatory activity. It was observed that even cerebral atrophy occurred even at times when the disease was not clearly active [18].

This literature review aims to highlight immunological aspects that can be attributed both to the diagnosis and treatment of MS.

Methodology

It is an integrative literature review, which allows the evaluation and synthesis of evidence and knowledge about the phenomenon studied, by understanding its current state, as well as proposing effective interventions in health care. For this, six methodological steps of the review were carried out. The first stage consisted in the elaboration of the hypothesis starting from a guiding question of the research, that is, identification of the problem, search engine to be adopted and the descriptors or keywords. The second step was the establishment of inclusion and exclusion criteria for the articles to be selected to compose the sample. The third stage was an exploratory reading of the abstracts, making a pre-selection of the studies. In the fourth stage, an analytical reading of the studies was carried out in order to gather, analyze and categorize the information pertinent to the investigated problem. In the fifth stage, the results were interpreted. In the sixth and final stage, the synthesis and presentation of the identified results was promoted, as well as recommendations for further studies.

Once the theme was defined, the following guiding question was elaborated: what is the evidence in the evolution of scientific production on approaches that can modify the immune response in patients with multiple sclerosis? The research on scientific production was carried out in 2020, through a bibliographic survey in the databases of the National Institutes of Health - PubMed, Electronic Scientific Online Library - Scielo and Latin American and Caribbean Health Sciences Information System - LILACS , in order to map articles relevant to the theme. For this purpose, the keywords multiple sclerosis, encephalopathies, encephalomyelitis, immunology, macrophages, lymphocytes, interleukins, autoimmunity, isolated and in association, were used in order to find similar themes published until today. Altogether, with the association of keywords, 41 articles were found. These were filtered with respect to Portuguese, English and Spanish, publications from January 2010 to June 2020, full texts online, being case reports, case series, original articles, retrospective, prospective and observational studies, with themes related to mechanisms related to multiple sclerosis immunopathogenesis and the main check points as immunotherapeutic targets (figure 01). Literature review articles, publications before January 2010 and after December 2020, languages other than English, Portuguese or Spanish, and articles do not complete in full or with themes that did not resemble the proposal in the work were also excluded (Figure 1).

Results and Discussion

In the time frame established for this study (2010-2020), 6 publications were found and analyzed. In 2014, 2015 and 2017 1 article (50%) was published each year respectively, in 2018 there are 2 publications (33.3%) and in 2019 only 1 publication in the year (16.7%). The publications resulted from different journals: Acta Medica Iranica, MAbs, Multiple Sclerosis Journal, Frontiers in immunology, JCI insight and Proceedings of the National Academy of Sciences (PNAS). Analyzing the study places of the articles, each one was carried out in a different location, being: Iran (16.6%), Switzerland (16.6%), USA (16.6%), Canada (16.6%), Australia (16.6%) and Spain (16.6%). Multiple Sclerosis (MS) is an autoimmune and neurodegenerative disease of the Central Nervous System (CNS) The pathophysiological process basically consists of an intense inflammatory process that evolves with demyelination and axonal loss [19]. This autoimmunity that evolves with inflammation is due to the imbalance of different subsets of T cells, especially those of the Th1 and Th17 profiles [20], associated with antibodies (IgG4) against myelin peptides [21].

Thus, currently, different aspects that explain this pathophysiology from infectious processes, autoimmune processes and genetic mutations. Based on these understandings, therapeutic measures have been developed, even if experimental, that can be used effectively for the clinical improvement of patients. An example of this is the clinical trial carried out with 13 patients, in which 10 received a complete therapeutic plan with specific T cells for the Epstein Barr virus (EBV), 4 with T cells with weak reactivity to the virus and 6 with high reactivity to the virus. Among those who received the dose of high reactivity, all had objective symptomatic neurological improvement, associated with reduction and fatigue. As for those who received low reactivity, only 25% showed improvement similar to the other group [22]. This is explained because in other studies it has been shown that EBV-specific T cell therapy should kill EBV-infected B cells in the CNS and thus prevent disease progression and lead to clinical improvement. And the relationship with MS is that EBV infection may be the precursor to the inflammatory process in the CNS [22]. In this perspective of devising a method of symptom improvement and even reaching the cure of MS, a Canadian clinical study, in phase 2, with 24 individuals, evaluated the autologous transplantation of hematopoietic stem cells to treat the aggressive form of MS. The researchers found that there was an increase in Natural Killers (NK) cells providing initial co-stimulation that supports the induction of a Th17 response, but followed by cytotoxicity which limits these cells. Thus, these data suggest that the rapid reconstitution of NK cells after transplantation contributes to suppressing the resurgence of Th17 cells and thus reducing the inflammatory process, which is at the heart of MS [20]. In this sense of suppression of T cells for remission and treatment of MS, a North American study, randomized double blind clinical study, with 123 individuals, evaluated the efficacy and safety of the co-stimulatory block made by the CTLA4-Ig fusion protein abatacept, when associated with T lymphocyte in MS. In general, there was neither clinical improvement nor reduction in the number of classic lesions on magnetic resonance imaging of the skull. However, since there was no worsening of the patients’ condition or the appearance of new lesions, these antibodies are potentially effective and there is a need for further studies [23].

As regarding to the use of monoclonal antibodies in the treatment and clinical improvement of patients with MS, a clinical study in phase 1, first developed on animals and already tested on 2 volunteers, showed that GNbAC1, a humanized IgG4 monoclonal antibody, targets the retrovirus envelope protein associated with MS, is promising and both animals and humans beyond its safety [24]. This specific study demonstrates the need for investment in research with monoclonal antibodies, mainly for safety and efficiency. Finally, it is worth mentioning that there are measures beyond direct therapy with the introduction of antibodies or transplants to improve the patient with MS. Randomized clinical trial, Iranian, carried out with 101 participants, of middle age, of both sexes, evaluated the effect of vitamin supplementation with the levels of cytokines and the genetic expression of patients already diagnosed with MS. It was concluded that 100% of the participants had a response to treatment, this being partial or total. Thus, evidencing that retinol and its metabolites have a promising possibility of preventing inflammatory processes in the CNS, in addition to the neurodegenerative process. This, therefore, shows regression of the disease [19].

In this sense, figure 02 summarizes the pathophysiological process of multiple sclerosis in terms of immunological aspects and possible checkpoints for the target therapy. The numbers 1 to 4 represent the etiopathogenesis of multiple sclerosis (MS). The letters A to C are the factors that modulate the immune response of MS. 1) In the presence of viral infections by Epstein-Barr (EBV) and multiple sclerosis-associated retrovirus (MSRV), an immune response is initiated. 2) LTCD4 are activated by antigen presenting cells (APC), such as microglia and B lymphocytes. They adopt a Th1 profile, producing IFN and TNF, and a Th17 profile, producing IL-17 and IL-22. 3) LB differentiate into plasmocytes, which will produce IgG4. 4) Neuronal inflammation occurs, which triggers demyelination due to the action of autoreactive lymphocytes. A) The IgG4 monoclonal antibody, GNbAC1, acts on the MSRV envelope protein. B) Abatacept CTLA4-Ig fusion protein performing costimulatory block when associated with LT. C) Retinol acting against inflammatory and neurodegenerative processes (Figure 2).

Final Considerations

MS is the most common chronic demyelinating disease of the central nervous system, resulting from a complex and dynamic interaction between the immune system, glial cells and neurons. However, it was evident that the criteria commonly used for the pathogenesis of MS lack immunological aspects that assist in the diagnosis and treatment of the disease. Therefore, it is concluded that there is a need for further research related to the immunological aspects attributed to the diagnosis and treatment of MS, which are linked to the reduction of the inflammatory response. Notwithstanding, clinical studies already underway lack incentive, given their promising results and the improvement in the quality of life of the patients involved.

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