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kashishipr · 3 years

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Three pharmaceutical companies, including Enzon Pharmaceuticals, Micromet AG, and Cambridge Antibody Technology (now acquired by AstraZeneca), in September 2003 announced signing a non-exclusive cross-license agreement. The agreement enabled the three parties involved to obtain Freedom to Operate (abbreviated as FTO), thereby authorizing one another to use some of their respective patented technologies without worrying about Patent Infringement. It also allowed them to research well and come up with therapeutic and diagnostic antibody-based products.

FTO is a pretty simple and straightforward concept, which implies that at a given point in time, no Intellectual Property (IP) from any third party is infringed upon a given product or service in a given market or geography. FTO agreements have now become common in certain sectors, particularly the IT sector, where there is extensive Patent Filing and risks involved in commercialization are being blocked by a competitor who holds a patented technology incorporated within some product. Without any doubt, stepping into patent litigation can be uncertain, full of risks, and expensive. Hence, business companies and firms look forward to ensuring at all times that the commercial production, use of their products, processes, services, or marketing activities don’t infringe upon the Patent Rights of others.

Although a complete guarantee of FTO will never be attainable, there are some ways (as mentioned below) of minimizing the risks involved that can help save a company its significant resources.

Conducting FTO Analysis Based on Patent Literature Search

An FTO analysis always starts with searching the patent literature and documents for granted or pending patents. It also involves obtaining a legal opinion corresponding to whether a process, product, or service may be considered infringing upon any patent or patents already owned by others.

When it comes to conducting FTO search and analysis, it is essential to note some of the limitations (as mentioned below) on patents that can offer potential opportunities to the companies and innovators:

Patent rights are territorial. It implies that while a specific technology may be protected in the main markets of a company, it may lie in the public domain in some other countries. In the latter case, no license or permission of any sort is required from the patent owner for commercializing the product.

Patents have a limited protection period. In most countries, they typically last for a maximum of 20 years, after which they lie in the public domain and can be freely used by anyone. Furthermore, as per the estimations of the European Patent Office (EPO), less than 25% of the patents issued through EPO are maintained well for the 20-year protection period as most of them usually lapse through non-payment of the patent annuities.

Patents have a limited scope, and it is defined in the claims section of a patent document. To be specific, any aspect of the invention not covered in the claims isn’t considered to be protected. However, in this case, it is imperative to note that determining the scope of a patent is not easy. It undoubtedly requires a lot of experience in interpreting the patent claims, the specifications, and the history of the Patent Application Process.

Overcoming Obstacles

Conducting an FTO analysis based on the search of patent documents and literature is only the first step. If the result of the patent search reveals that there exist one or more patents limiting a firm’s FTO, the firm needs to decide well on how to proceed. In the scenario where the blocking patent is valid, firms and companies can consider the following options:

Licensing or Patent Purchasing – The licensing process involves obtaining written consent from the patent owner to use the patented technology in some specific markets for some specific acts and a specified period. The convenience of a licensing agreement majorly depends on the terms and conditions mentioned in it. While there is a possible loss of autonomy, and the patent owner will require payment of a lump sum amount or royalties from time to time, it may still be the simplest way of clearing the obstacles concerning the commercialization of some new technology or product.

Inventing Around the Invention – It usually involves doing some R&D for making some changes to a process or product so as to avoid infringing upon the patent or patents owned by others in the market. For instance, if the FTO is limited by a product patent, a firm can consider developing an alternative product to arrive at a pretty similar end result, thereby successfully commercializing the invention without paying a licensing fee to some other person.

Cross-Licensing– It involves two or more firms exchanging licenses for being able to use the patented inventions owned by one another. For cross-licensing, a firm needs to own a well-safeguarded patent portfolio that offers considerable worth to the potential licensing parties.

Patent Pools– It is a mechanism under which two or more firms practicing similar technologies put their patented inventions in a pool to create a clearinghouse for the respective patent rights.

Seeking Patent Protection for the Technology

If the patent analysis and search show that there are no patents blocking access to the market, and the new technology is likely to be eligible for patentability, a business owner or innovator may look forward to obtaining Patent Protection for ensuring a greater degree of FTO, in place of just keeping it as a trade secret.

There is, however, a well-defined limit corresponding to which a patent holder has the FTO. In itself, a patent doesn’t offer the right to commercialize the patented technology but only prevents others in the market from doing so, and it is indeed a crucial distinction. Therefore, if a company or firm is looking forward to commercializing its technology, it may require using the patented technologies of others. Despite all these factors, FTO is still one of the major reasons behind big companies and firms applying for patent protection. Although the grant of a patent in itself is not enough to clear the path for commercialization, it is indeed a beneficial step and helps prevent a lot of problems down the road.

Opting for Technical Disclosures or Defensive Publishing

Many reasons exist behind a firm or company avoiding seeking patent protection for a given invention, including the cost or the concern that the invention might not be eligible for patentability. An alternative that businesses sometimes opt for is technical disclosures or defensive publishing, which is a total contrast to keeping the invention as a trade secret. This mechanism focuses on disclosing an invention to the public to ensure that nobody else patents it. It offers some degree of FTO to everyone. In this case, it is essential to note that the disclosure should be made in a well-acknowledged technical journal or some other publication that is most likely to be consulted by the patent examiners for examining the Patent Applications.

Bottom Line

No matter what means is chosen, technology firms and companies are always recommended to consider all the available options well in advance. In some circumstances, paying a licensing fee to the patent holder or coming up with minor product adaptations may be sufficient in avoiding future conflicts. Analyzing a firm’s FTO adequately before releasing a new product is, therefore, a brilliant way of minimizing the risks involved in infringing upon the patented inventions owned by others. Doing the same shall also enhance a firm’s chances of coming across suitable business investors and partners for supporting its development plans and strategies. ✅ For more visit: https://www.kashishipr.com/

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bearni · 3 years

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Global PEGylated Protein Therapeutics Market By Type (Colony Stimulating Factor,Interferon,Erythropoietin (EPO),Recombinant Factor VIII,Monoclonal Antibody,Enzyme), By Application (CancerAutoimmune DiseaseHepatitisMultiple SclerosisHemophiliaGastrointestinal Disorder), By Country, and Manufacture - Industry Segment, Competition Scenario and Forecast by 2029

Industry analysis and future outlook on PEGylated Protein Therapeutics Global Market brings a systematic perspective of the market execution and assists in strategic decision making for worldwide and additionally the regional situation. Detailed sections provides in-depth arrangement, the PEGylated Protein Therapeutics contemplate that make sense of different perspectives relating to the global market. To begin with, the PEGylated Protein Therapeutics market definition, applications, arrangement, and industry esteem chain structure are incorporated into the answer, to target gathering of people on restricting PEGylated Protein Therapeutics market elements including drivers, limitations, openings, patterns, applications, topographical/local PEGylated Protein Therapeutics markets, and aggressive scene.

Global PEGylated Protein Therapeutics Industry Market was valued at USD XX Million in the year 2020. The market is further estimated to grow at a CAGR of XX% from 2020 to reach USD XX Million by the year 2029.

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PEGylated Protein Therapeutics market rivalry by top makers/players, with PEGylated Protein Therapeutics deals volume, Value (USD/Unit), Revenue (Mn/Bn USD) and market size for every producer/player; the significant players include:

Merck Pfizer UCB Amgen AstraZeneca Biogen Roche Horizon Pharma Leadiant Biosciences

Worldwide PEGylated Protein Therapeutics statistical surveying report uncovers that the PEGylated Protein Therapeutics business will develop with pivotal CAGR over the estimated forecast period of 2021 and 2029. The global PEGylated Protein Therapeutics market in forecast years 2021-2029, is expected to hit Mn/Bn$ XX USD by 2029. The PEGylated Protein Therapeutics market gives broad development openings over the both created and creating economies. Further, the PEGylated Protein Therapeutics business sectors could profit without a doubt from the expanding interest to bring down PEGylated Protein Therapeutics expenses of treatment over the globe.

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Key Highlights of the Report:

PEGylated Protein Therapeutics Market Report provides forecast and industry outlook for the period of 2021-2029 with 2020 as the base year and covering historic data for years 2015-2019.

PEGylated Protein Therapeutics Market outlook with Porter’s 5 Forces Analysis will provide market dynamics (Drivers, Restraints, Opportunities & Threats).

PEGylated Protein Therapeutics Competitive landscape section gives you the competitive edge over other key players in the market (Key Business Strategies, Recent Development M&A, Company Overview, Products/Services Portfolio & Financial Overview).

PEGylated Protein Therapeutics Technological Scenarios & Expected Developments.

PEGylated Protein Therapeutics End-Use Industry & Consumer Behaviour Trends.

PEGylated Protein Therapeutics Export-Import Scenario.

PEGylated Protein Therapeutics Regulatory Policies across each region.

PEGylated Protein Therapeutics In-depth analysis on Industry Trends & Dynamics across each segment covered in the report.

Based on Type, PEGylated Protein Therapeutics market report shows development rate of each type, covers:

Colony Stimulating Factor Interferon Erythropoietin (EPO) Recombinant Factor VIII Monoclonal Antibody Enzyme

End clients/applications, PEGylated Protein Therapeutics market report centers around the status and viewpoint for best applications/end clients, development rate for every application, this can be isolated into:

Cancer Autoimmune Disease Hepatitis Multiple Sclerosis Hemophilia Gastrointestinal Disorder

Access More Information at: https://www.globalresearchview.com/report/global-pegylated-protein-therapeutics-ma/GRV52907

In conclusion, the global PEGylated Protein Therapeutics industry report unveils research finding, outcomes, conclusions. Likewise, disclose various PEGylated Protein Therapeutics data sources, traders/vendors, suppliers, manufacturers, sales channel, and addendum. In short, the overall PEGylated Protein Therapeutics report is a lucrative document for people implicated in PEGylated Protein Therapeutics market.

Global Impact of COVID-19 Analysis:

COVID19 is an unrivaled global public health emergency that affects almost every industry, so the projected long-term impact will affect industry growth over the forecast period. The report provides insights into COVID19, taking into account changes in consumer behavior and demand, purchasing behavior, supply chain diversion, the dynamics of current market forces, and significant government intervention. Insights, analysis, estimates and forecasts considering the impact of COVID19 on the market.

About Us:

GlobalResearchView (GRV) is one of the leading market research company which aims to serve the most excellent research to the various sectors of business. We are prominent in satisfying all kinds of market research needs.

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#Global Pegylated Protein Therapeutics Market World Pegylated Protein Therapeutics Market Europe Pegylated Protein Therapeutics Market Uk Peg

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vinabinatina · 3 years

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#market analysis

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moleculardepot · 8 months

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EPO Monoclonal Antibody

EPO Monoclonal Antibody Catalog number: B2015338 Lot number: Batch Dependent Expiration Date: Batch dependent Amount: 10 μg Molecular Weight or Concentration: N/A Supplied as: Solution Applications: a molecular tool for various biochemical applications Storage: -20°C Keywords: EPO Monoclonal antibody Grade: Biotechnology grade. All products are highly pure. All solutions are made with Type I…

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ipandlegalfilings · 3 years

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EPO's Biotech Examination Guidelines 2021

European Patent Office comes up with its new Guidelines for Examination 2021 with effect from March 1. Through these guidelines, EPO touches upon the aspects of Biotech concerning the biological process, therapeutic method, and antibody. Read more: https://bit.ly/3d6cgL3

#EPOExam21 #guidelines #ipandlegalfilings

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bostorbio · 3 years

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EPO (Epo antibody) is a gene with five exons and four intros that is discovered on chromosome 7. This gene produces a 193-base amino acid chain as a transcriptional product.

#Epo antibody

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bigfandeer · 3 years

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Biosimilars Market Size Worth US $ 16.97 Billion By 2025 | CAGR: 26%

Overview

A Biosimilar is described as a biological, medical product which is an identical copy of the original medical product. Market Research Future (MRFR) has published and released a research report about the global biosimilars market that predicts massive enlargement for this market with 26% CAGR during the forecast period between 2016 and 2023. In terms of cash, the market has been anticipated to rise to the US $ 16.97 bn.

Get Request Free Sample @ https://www.marketresearchfuture.com/sample_request/1329

Analyzing the market structure, this report estimates the future growth potential of the market. It observes the strategies of the key players in the market and follows the competitive developments like joint ventures, new product developments, mergers and acquisitions, research and developments (R & D) in the market. This report also covers insights on the major countries/regions in which this industry is flourishing, along with the list and description of untapped regions which could be the potential markets in the future.

The key factors aiding the growth of the global biosimilars market include clinical trial activities for biosimilars, increasing demand for the cheap medical products, increasing incident of different diseases, and strategic collaborations resulting in enhanced productivity. However, lack of awareness and physician skepticism are the major restraining factor regarding market growth.

The segmentation global biosimilars market is on the basis of application, manufacturing, product, and region. The application based segmentation segments the market into blood-related disorders, immunity-related diseases, oncology, and other. Based on manufacturing, the market has contract manufacturing and in-house manufacturing. As per segmentation based on product, the market has been segmented into recombinant glycosylated proteins, recombinant non-glycosylated proteins, and others. Recombinant glycosylated proteins have been further segmented into Monoclonal antibody (mAb) and EPO. Recombinant non-glycosylated proteins have been further segmented into growth hormones, insulin, and other.

The regional segmentation of the global biosimilars market segments the market into continent-based regional markets namely Asia Pacific, North America, Europe, and rest of the world (RoW). According to the report, Europe is the biggest regional market for the biosimilars due to the advanced medical research, increasing the prevalence of diseases and rising geriatric population. Due to technological advancement, Western Europe is a bigger market than Eastern Europe. The key country-specific markets in Western Europe include France, Italy, Spain, Germany, and the United Kingdom (UK), followed by the rest of Western Europe.

North America is the second largest market, being ahead of Europe in terms of technological advancement and being equal to Europe in terms of medical research. North America‘s approach towards biosimilars is not as welcome as Europe‘s is. Major country-specific markets in North America are Canada and the United States of America (USA). The Asia Pacific has been expected to emerge as the fast-growing market during the forecast period. The country-specific markets generating maximum revenue in this region are Australia, India, Japan, South Korea, and China, followed by the rest of the Asia Pacific region.

Key Players

The key players in the global biosimilars market include Accord Healthcare (UK), Amgen Inc. (USA), Astra Zeneca (UK), Biocon Ltd. (India), Celltrion, Inc. (South Korea), Dr. Reddy’s Laboratories Ltd. (India), Eli Lilly (USA), F. Hoffmann-La Roche Ltd. (Switzerland), Novartis (Switzerland), Pfizer Inc. (USA), Samsung Bioepis (South Korea), Sandoz International GmbH (Germany), and Teva Pharmaceuticals Industries Ltd. (Israel).

Latest Industry News

Mundipharma, a network of independent pharma companies, has acquired Spanish biosimilars development company Cinfa Biotech. The deal gives Mundipharma, access to a biosimilar to Amgen’s Neulasta (pegfilgrastim). 10 OCT 2018

The new white paper issued by the Association of European Cancer Leagues, a nonprofit, pan-European organization of national and regional cancer societies, has called for the greater use of biosimilars as a means to increase patient access to cancer treatment, and reduce costs. 10 OCT 2018

Table of Contents

1. REPORT PROLOGUE

2. MARKET INTRODUCTION

2.1. Definition

2.2. Scope of the Study

2.2.1. Research Objective

2.2.2. Assumptions

2.2.3. Limitations

3. RESEARCH METHODOLOGY

3.1. Overview

3.2. Primary Research

3.3. Secondary Research

3.4. Market Size Estimation

4. MARKET DYNAMICS

4.1. Overview

4.2. Drivers

4.3. Restraints

4.4. Opportunities

5. MARKET FACTOR ANALYSIS

5.1. Porter’s Five Forces Analysis

5.1.1. Bargaining Power of Suppliers

5.1.2. Bargaining Power of Buyers

5.1.3. Threat of New Entrants

5.1.4. Threat of Substitutes

5.1.5. Intensity of Rivalry

5.2. Value Chain Analysis

Browse Complete Report @ https://www.marketresearchfuture.com/reports/biosimilars-market-1329

About Market Research Future:

At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half- Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research & Consulting Services. MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by Components, Application, Logistics and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions. In order to stay updated with technology and work process of the industry, MRFR often plans & conducts meet with the industry experts and industrial visits for its research analyst members.

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vaibk007 · 4 years

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Global PEGylated Proteins Market Research Report Cover Covid-19 Impact

The report presents an in-depth assessment of the PEGylated Proteins market including enabling technologies, key trends, market drivers, challenges, standardization, regulatory landscape, deployment models, operator case studies, opportunities, future roadmap, value chain, ecosystem player profiles, and strategies. The report also presents forecasts for PEGylated Proteins investments from 2020 to 2025.

“This is the latest report, covering the current COVID-19 impact on the market. The pandemic of Coronavirus (COVID-19) has affected every aspect of life globally. This has brought along several changes in market conditions. The rapidly changing market scenario and initial and future assessment of the impact are covered in the report.”

In the global PEGylated Proteins market, the following companies are covered: Merck Sharp & Dohme, ENZON Pharmaceuticals, Roche, Pfizer, Amgen, UCB, Crealta (Savient)

SPECIAL OFFER (Avail a flat 20% discount on this report)

Click the link to get a free Sample Copy of the Report at:

https://www.reportsnmarkets.com/request_sample.php?id=51053

Market Segment by Product Type:

Colony Stimulating Factors

Interferons

Erythropoietin (EPO)

Recombinant Factor Viii

Monoclonal Antibodies

Others

Market Segment by Application:[i]

Cancer Treatment

Hepatitis

Chronic Kidney Disease

Leukemia

SCID

Rheumatoid Arthritis & Crohn's Disease

Others

Key Regions split in this report: breakdown data for each region,

Asia-Pacific[China, Southeast Asia, India, Japan, Korea, Western Asia]

Europe[Germany, UK, France, Italy, Russia, Spain, Netherlands, Turkey, Switzerland]

North America[United States, Canada, Mexico]

Middle East & Africa[GCC, North Africa, South Africa]

South America[Brazil, Argentina, Columbia, Chile, Peru]

Buy Exclusive Report:

https://www.reportsnmarkets.com/checkout?id=51053

Influence of the PEGylated Proteins market report:

-Comprehensive assessment of all opportunities and risks in the PEGylated Proteins market.

-PEGylated Proteins market recent innovations and major events.

-A detailed study of business strategies for the growth of the PEGylated Proteins market-leading players.

-Conclusive study about the growth plot of the PEGylated Proteins market for forthcoming years.

-In-depth understanding of PEGylated Proteins market-particular drivers, constraints, and major micro markets.

-Favorable impression inside vital technological and market latest trends striking the PEGylated Proteins market.

The report has 150 tables and figures browse the report description and TOC:

https://www.reportsnmarkets.com/report/-COVID-19-Version-Global-PEGylated-Proteins-Market-Status-2015-2019-and-Forecast-2020-2025-by-Region-Product-Type-End-Use-51053

What are the market factors that are explained in the report?

-Key Strategic Developments: The study also includes the key strategic developments of the market, comprising R&D, new product launch, M&A, agreements, collaborations, partnerships, joint ventures, and regional growth of the leading competitors operating in the market on a global and regional scale.

-Key Market Features: The Global PEGylated Proteins market report evaluated key market features, including revenue, price, capacity, capacity utilization rate, gross, production, production rate, consumption, import/export, supply/demand, cost, market share, CAGR, and gross margin. In addition, the study offers a comprehensive study of the key market dynamics and their latest trends, along with pertinent market segments and sub-segments.

-Analytical Tools: The Global PEGylated Proteins Market report includes the accurately studied and assessed data of the key industry players and their scope in the market by means of a number of analytical tools. The analytical tools such as Porter’s five forces analysis, SWOT analysis, feasibility study, and investment return analysis have been used to analyze the growth of the key players operating in the market.

The research includes historic data from 2015 to 2020 and forecasts until 2025 which makes the reports an invaluable resource for industry executives, marketing, sales and product managers, consultants, analysts, and other people looking for key industry data in readily accessible documents with clearly presented tables and graphs.

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ratiram · 5 years

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According to study, “Global PEGylated Proteins Market 2019 by Manufacturers, Regions, Type and Application, Forecast to 2024” the key companies operating in the global market areENZON Pharmaceuticals, Roche, Merck Sharp & Dohme, Crealta (Savient), Pfizer, UCB, Amgen, Thermo Fisher Scientific Inc., Jenkem Technology, Celares GmbH, NOF American Corp., Creative PEGworks, Quanta Biodesign Ltd., Laysan Bio Inc., IRIS BioTech GmbH, Biomatrik Inc.

PEGylation is a process of covalent & non-covalent attachment of polyethylene (PE) glycol polymer chains to molecules, such as a therapeutic protein, drug, or vesicle. It improves stability & solubility of drug and decreases immunogenicity through changing the electrostatic binding, hydrophobicity and confirmation of the molecule. It decreases the dose frequency by reducing renal excretion & proteolysis, and rises tension time of conjugates in blood & stability of drug. PEGylation proteins enhanced the management of numerous chronic diseases, including leukemia, cancer, hepatitis C, severe combined immunodeficiency disease, rheumatoid arthritis, and Crohn’s disease. Pegaspargase, pegaptanib, pegfilgrastim, certolizumabpegol, pegademase bovine,pegvisomant, and interferons are the most important PEGylated drugs.

Based on product type,PEGylated proteins market is segmented into services and consumable. Services are further sub-segmented into development of analytical methods, development of PEGylatedbiosimilars, pilot production of peg drug conjugate,process development of peg-drug conjugate manufacturing and Pegylationfeasibility studies services. Consumable products are further sub-segmented into PEGlyation reagents and PEGylation kits. Pegylation reagents include branched PEGs, Mono-functional linear PEGs, multi-arm PEGS, bi-functional PEGS and other PEGylation reagents. Based on protein type, market is segmented into colongy stimulating factors, recombinant factor viii, interferons, monoclonal antibodies, Erythropoietin (EPO) and other protein type.Based on process type, market is segmented into enzymatic PEGylation, chemical PEGylation, and genetic PEGylation. Based on sales channel, market is segmented into online providers, hospital pharmacy, retail pharmacy and others. Based on application, market is segmented into chronic kidney disease, cancer treatment,HEPAtitis, gastrointestinal disorder, hemophilia, multiple sclerosis and other applications. In addition, based on end-user, market is segmented into contract research organization, pharmaceutical & biotechnology companies, academic research institutes and others. The pharmaceutical & biotechnology segment is expected to witness high growth during the forecast period due to rise in research & development (R&D) spending in pharmaceutical & biotechnology sectors globally.

The PEGylated proteins market is driven by increase in adoption of protein-based drugs over non-protein-based drugs, followed by rise in R&D spending, high prevalence rate of lifestyle diseases, growth in biologics sector and surge in protein’s stability & circulating half-life. However failure of drug development & recall of products and high costs associated with drug development may impact the market. Moreover, growth in adoption of PEGylated protein therapeutics and untapped emerging economies are key opportunities for market.

Based on geography, the North-American and European regions hold major share in PEGylated proteins market owing to rise in awareness about the disease among patients and increase in available therapies in the regions. The Asian-Pacific region is projected to witness fastest growth rate due to growth in prevalence of lifestyle diseases, rise in medical tourism and increase in health care spending over the forecast period. It is predicted that future of the market will be bright caused by rise in mortality rates associated with chronic ailments and growth in incidence of cancer during the forecast period. The worldwide market is estimated to grow at a CAGR of approximately 3.9% over the next five years, will reach US $3910 million in 2024, from US $3230 million in 2019.

For more information on the research report, refer to below link:

Global PEGylated Proteins Market

Related reports

Global PEGylated Proteins Market Status (2015-2019) and Forecast (2020-2024) by Region, Product Type & End-Use

PEGylated Proteins Market Research: Global Status & Forecast by Geography, Type & Application (2015-2025)

Global PEGylated Proteins Market Analysis 2013-2018 and Forecast 2019-2024

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#세계적인 pegylated 단백질 시장

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siva3155 · 5 years

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300+ TOP CASE MANAGER Objective Questions and Answers

CASE MANAGER Multiple Choice Questions :-

1.Which of the following is a responsibility of a case manager: A. Avoid subject material in documentation. B. Making medical decisions if the patient is unable to do so. C. Obtain medical services for an incapacitated patient. D. Obtain financial services for an incapacitated patient. ANS:- A 2. After obtaining work capacity documentation: A. The case manager should perform job analysis. B. The case manager should determine whether an IME is appropriate. C. The case manager should determine appropriateness of work-hardening process. D. The case manager should submit documentation to the employer and insurance company. ANS:- D 3. What is meant by annulus: A. It is a sign of a herniated disc. B. It is the outer portion of an intervertebral disc. C. It is the inner portion of an intervertebral disc. D. It is a medical procedure which is not common due to pain involved. ANS:- B 4. A meaning of the root word "myel" is: A. Spinal cord B. Muscle C. Cartilage D. Largeness ANS:- A 5. Which of the following are bisphosphonates used to prevent and treat osteoporosis in postmenopausal women? A. Evista and fosamax B. Alendronate and risedronate C. Estrogen and raloxifene D. Estrogen and alendronate ANS:- B 6. A transfer penalty: A. Is only incurred if assets are given away to a spouse. B. Is a period of time during which enrollee is not eligible for Medicaid. C. Is incurred when enrollee has given away assets; enrollee is no longer eligible for Medicaid. D. Is a penalty fine incurred when the enrollee has given away assets. ANS:- B 7. What is the Out of Area (OAC)? A. Physicians who are located outside a prescribed geographic radius B. Treatment that is only available at a facility that does not lie within the geographic radius included in the subscribed healthcare plan C. The treatment received by a member of a health care plan when he/she is out of the network coverage area D. Hospitals and facilities that are outside the geographic boundaries of the available approved providers ANS:- C 8. In which model is care only reimbursed when paneled providers are used? A. EPO (Exclusive Provider Organization) B. IPA (Independent Practice Association) C. Group Model D. Staff Model ANS:- A 9. What is meant by Functional impairment:? A. It is an indicator of crisis likelihood. B. It is the temporary exchange of roles to cope with a disability. C. It is the ability of a client's family to provide for the client's needs and still function. D. It is when overwhelming distress hinders coping ability. ANS:- A 10. The age group with the highest suicide rate: A. Are people among the 10-24 year old age group. B. Are white men over the age of 85. C. Are people among the 10-14 year old age group. D. Are people among the 15-24 year old age group. ANS:- B

CASE MANAGER MCQs 11. Patient participation in pain treatment: A. Is a maladaptive coping behavior. B. Is not suggested by JCAHO. C. Is only necessary if the patient is without an appropriate provider. D. Is an adaptive coping mechanism. ANS:- D 12. In legal terms, define "discovery period." A. This is not a legal term B. The time in which all material evidence has to be produced and exchanged C. Time where mediation takes place D. Time were all parties involved get together to resolve differences ANS:- B 13. What is a Transcranial Doppler: A. Assesses extent or location of injured brain tissue. B. Provides 3-dimensional pictures of tissues. C. Is a lengthy process assessing cognitive abilities or deficits. D. Assesses brain's arterial circulation. ANS:- D 15. What is a nasal polyps? A. Inflamed sinus B. Inflamed rhinitis C. Inflamed nasal cavity D. Inflamed nasal mucosa ANS:- D 16. What is the fullform of CPT-4? A. Caseworkers with Professional Training, 4th year B. Current Procedural Terminology C. Caregivers Professional Tribute, 4th year D. Caseworkers with Physical Techniques, 4th year ANS:- B 17. What does a correlational study determine? A. The relationship between two occurrences B. The effects of A on B C. Cause-effect D. The effects of B on A ANS:- A 18. Which of the following is an accurate statement about prescription drug coverage for seniors: A. Prescription drug coverage is expected to remain at its current situation, until reform is implemented. B. Prescription drug coverage is expected to improve. C. Prescription drug coverage is expected to decline. D. Prescription drug coverage is a functioning benefit of Part B Medicare insurance. ANS:- C 19. What is DSM-IV? A. Doctors Synthesis of Manuals- 4th edition B. Diagnosis of Sexual Manifestations- 4th edition C. Doctors Standards for Medications, 4th edition D. Diagnostic and Statistical Manual of Mental Disorders ANS:- D 20. Which of the following statements is untrue regarding crisis? A. There are two types of crisis; developmental and situational B. Crises are either resolved positively or negatively in a brief period of time C. A crisis is usually preceded by a particular identifiable event D. There are three type of crisis; developmental, situational, and individual ANS:- D 21. The following is a high potency antipsychotic: A. Clozaril B. Thorazine C. Mellaril D. Haldol ANS:- D 22. The breathing capacity of the lungs is measured through: A. Electromyography B. Spirometry C. Clinical observation D. Fluorescent antinuclear antibody test ANS:- B 23. Time out of work under worker's compensation may be included in the FMLA twelve week period: A. Only if the employee is offered COBRA by the employer. B. If the employee is out of work for a period over 18 months. C. If the employee is notified in writing. D. If the employer agrees to hold the employees position for more than the twelve-week period. ANS:- C 24. If a Medicare recipient does not enroll in Part B insurance when he enrolls in Part A insurance: A. The recipient may purchase Part B Medicare afterward, but will experience a rise in Part B premiums until he enrolls in Part B. B. The recipient may not purchase Part B Medicare afterward. C. The recipient may purchase Part B Medicare afterward, and will not experience a rise in premiums. D. The recipient may purchase Part B Medicare afterward, but will experience a rise in Part A premiums until he enrolls in Part B. ANS:- A 25. Of the following test instruments, which would give you the most reliable results? A. MAPI B. Ruler C. House-Tree-Person D. Beck Depression Inventory ANS:- B 26. Which is not a category of mental disorder contained in the DSM IV? A. Anxiety Disorders B. Diagnostic Disorders C. Cognitive Disorders D. Mood disorders ANS:- B 27. An incomplete injury is one in which: A. There is no communication between the outside body and the spinal cord. B. There is some communication between the outside body and the spinal cord. C. There is no signal whatsoever traveling through the site of injury. D. There are some signals traveling through the site of injury. ANS:- D 28. Disability coverage programs: A. May have limits of several years, or last until retirement age. B. Typically end after a period of several years. C. Invariably end after a two year duration. D. Must continue until age of retirement. ANS:- A 29. The DSM-IV defines Anxiety as: A. An impoverishment in thinking that is inferred from observing speech and language behavior B. An inability to initiate and persist in goal-directed activities. C. The apprehensive anticipation of future danger or misfortune accompanied by a feeling of dysphoria or somatic symptoms of tension D. Waxy flexibility-rigid maintenance of a body position over an extended period of time. ANS:- C 30. Client abandonment is: A. Termination of case management services. B. A case manager's failure to annually renew criteria of consent for client. C. Lack of sufficient termination notice resulting in harm to Client. D. Lack of sufficient understanding of client necessity for additional services. ANS:- C 31. What is meant by Bed Days:? A. The number of days a physician requires a client to remain on bed rest B. The number of days a hospital will willingly provide a bed for a client C. The number of actual days a client stays in hospital or another facility D. The number of beds available in a hospital on any given day ANS:- C 32. The following statement is not true with regard to bipolar disorder : A. Bipolar disorder is looked at as a biological disorder B. Bipolar disorder runs in families C. Prophylactic treatment is not typically warranted D. The primary medication to treat bipolar disorder is lithium ANS:- C 33. When conflict is _______________, it is emotional and focused on personal incompatibilities or disputes. A. High B. Dysfunctional C. Emotional D. Beneficial ANS:- B 34. The low use of formal power had a strong _______________ effect on interdisciplinary team collaboration . A. Influential B. Negative C. Collaborative D. Positive ANS:- D 35. Which is not a requirement for states to receive Federal-matching funds? A. AIDS screening for high-risk individuals B. Medical and surgical dental services C. Early and periodic screening, diagnosis and treatment services for people under 21 years of age D. Inpatient hospital services ANS:- A 36. When a stressful situation is so overwhelming that it blocks the client's effective coping ability: A. It is called disruption of homeostasis. B. It may be an indicator of a client's ability to effectively handle disability. C. It is called crisis. D. It is called functional impairment. ANS:- C 37. According to the DSM IV, a poly substance dependence is: A. A use of at least three substances simultaneously B. A use of at least three substances in a short period C. A use of at least three groups of substances in one year D. A use of at least three substances in any given time frame ANS:- C 38. Which is true of a EPO? A. Care is not reimbursed if non-panel/non-network physicians are used B. Does not use gatekeeper approach services C. It combines elements of HMO and Indemnity Plan D. Subscriber pays little or nothing out-of-pocket ANS:- A 39. What is AAPCC? A. Ambulatory Americans Paying Cost of Care B. Americans for abortion classified committee C. American Association of Physicians Concerned about Costs D. Adjusted Area Per Capita Cost ANS:- D 40. Depression is an example of: A. A long-term positive coping technique. B. A short-term positive coping technique. C. A stressor. D. A maladaptive coping behavior. ANS:- D 41. What is Pooling? A. The act of combing the risk of all the groups in several groups into one risk pool B. The act of pooling resources of various individual subscribers so as to make the cost of healthcare more manageable for all members of the group C. The act of pooling resources by a group of hospitals so as to better manage the cost of healthcare D. The bundling together of various network providers so as to compile a more effective and varied list of providers ANS:- A 42. A concussion is: A. An open injury B. A type of skull fracture. C. A violent shaking of the brain. D. A bruise on brain tissue. ANS:- C 43. The AAPPCC is used by CMS A. As a means of estimating outlier expenses in a hospital setting B. as a basis of payments to managed care plans C. To limit healthcare benefits to specific covered conditions D. As a way to define who qualifies for health care under a particular managed care plan ANS:- B 44. Medicare is available to: A. All US citizens or permanent residents with disabilities. B. All US citizens or permanent residents over age 65 who have paid Medicare taxes, have a disability , or are diagnosed with kidney failure. C. All US citizens or permanent residents without resources for medical payment. D. All US citizens or permanent residents over age 65 who have paid Medicare taxes. ANS:- B 45. A quality system only _______________ the positives on what needs to be worked on. A. Eliminates B. Enhances C. Submits to D. Completes ANS:- B 46. Who most often provides rehabilitation services to Social Security beneficiaries? A. County agencies B. Private sector C. Federal agencies D. State rehabilitation agencies ANS:- D 47. The size of the lump sum payment to a hospital is based on A. The relative weight of the particular DRG B. The DRG C. Prospective reimbursement payment D. Omnibus budget reconciliation actions ANS:- A 48. An individual sustaining a sacral injury: A. Will become a paraplegic and lose function of the chest, abdomen, and other areas. B. May retain function of most areas, depending upon extent of injury. C. Will become a quadriplegic and may require a ventilator. D. May possibly be rendered paraplegic, depending upon extent of injury. ANS:- B 49. The reliability of an assessment tool is an indicator of: A. Faking good or faking bad B. Whether the assessment tool is measuring what it is supposed to measure C. How dependable the assessment tool is D. How effective the assessment tool is with different cultural populations ANS:- C 50. Which of the following statements regarding antidepressants is true? A. When an individual feels better he/she can stop taking antidepressants B. Antidepressants can make one feel "normal" C. Antidepressants are very effective when taken without other forms of intervention D. Antidepressants are addictive ANS:- B CASE MANAGER Objective type Questions with answers 51. What is meant by ICD-9CM? A. Internal Causative Dictionary , with clinically modified explanations B. Internal Classification of Disease the Clinical Modification C. International Classified Dictionary of the 9 clinical moods D. International Committee of Doctors, 9th clinical module ANS:- B 52. Due to its short half-life, which of the following requires a divided dosing? A. Paxil B. Prozac C. Elavil D. Wellbutrin ANS:- D 53. Individual Identifiable Health Information refers to: A. It also includes the provision of healthcare and payment for the provision of the insurance carrier B. Health records from the time of birth C. Any information related to a past, present or future physical or mental health condition D. All vaccination records ANS:- B 54. _______________ or formal power is control of something or someone. A. Dominance B. Equal power C. Conflict resolution D. Unequal power ANS:- A 55. Which is NOT a requirement to be met for the Social Security Administration to consider a person "disabled"? A. Physical or mental impairment B. Cannot do substantial gainful work C. Inability to get work D. Unable to do previous work ANS:- C 56. The elements of consent criteria: A. Must be initiated once, and renewed annually. B. Must be initiated once, and renewed on a monthly basis. C. Must be initiated once upon beginning case management. D. Must be initiated once, and renewed at each subsequent meeting with case manager and client. ANS:- A 57. What is meant by Disability? A. Refers to people who have a work history B. Means that an individual cannot work C. Refers to physical impairment only D. Refers to physical or mental impairment that substantially limits one or more of the major life activities of the individual. ANS:- D 58. If an employer wants to discontinue health benefits for an employee who has taken leave for more than twelve weeks: A. He may; according to FMLA the employer may discontinue health benefits at that point. B. He may not; according to COBRA, the employer must provide healthcare benefits for terminated employees for up to 18 months. C. He may; however, the employee must be notified in writing. D. He may; however the employer must offer the employee the option to purchase insurance at his group rate. ANS:- D 59. Usually health insurance coverage for a employee begins: A. Immediately upon selecting coverage B. When the insurance provider receives the paper work C. 3 months after they start work D. 30 days after starting employment ANS:- C 60. Which of the following is a key component of Medicare's partnership with the home care industry to monitor and facilitate improved home health care results? A. APC B. OASIS C. OBQI D. HHA ANS:- B 61. An individual sustaining a lumbar injury: A. Will become a paraplegic and lose function of the chest, abdomen, and other areas. B. May retain function of most areas, depending upon extent of injury. C. Will become a quadriplegic and may require a ventilator. D. May possibly be rendered paraplegic, depending upon extent of injury. ANS:- D 62. Which is true of anxiety disorders? A. PTSD and OCD are two forms of anxiety disorder. B. Anorexia nervosa is a form of anxiety disorder. C. They are defined by significant cognitive deficiencies. D. They are often accompanied by somatic symptoms. ANS:- B 63. Cortisone injections: A. Are used for neither diagnoses nor treatments. B. Are used for both diagnoses and treatments. C. Are only used for repetitive motion disorder diagnoses. D. Are only used for repetitive motion disorder treatments. ANS:- B 64. State employment services offices employ: A. The General Aptitude Test Battery B. House-Tree-Person Test C. The Symptom Checklist 90-R D. Maslach Burnout Inventory ANS:- A 65. An assessment tool's reliability is responsible for its: A. Upper limit of validity B. Lower limit of validity C. Test-retest limits D. Test-reliability limits ANS:- A 66. Which of the following would indicate a problem with color vision? A. inability to distinguish red from green B. inability to vocalize color names C. inability to differentiate between shades of gray D. lack of knowledge regarding relationships of tints and hues ANS:- A 67. Medicaid is funded by: A. Federal governments. B. Both federal and state governments. C. Stage governments. D. The CMS. ANS:- B 68. Defamation may be defined as: A. Failure to take due care or carelessness. B. Professional misconduct or negligence. C. Taking from one's reputation. D. A civil injury committed against another person or their property. ANS:- C 69. The best way for a Case Manager to obtain the most accurate data from a client is to: A. Review the client's chart B. Use close-ended questions C. Retrieve information from the client's caregiver and ask if they concur with the findings D. Use open-ended questions ANS:- D 70. Which is true of Medicare? A. It pays 100% of rehabilitative services and other hospital services and supplies for the first year in a skilled nursing facility B. It does not cover hospice care C. It pays 100% of approved amount for durable medical equipment as part of a home care treatment D. It pays 100% of approved amount for home health care ANS:- C 71. "Sedentary" is: A. A vocationally qualified level B. A skill level C. An exertion level D. An educational level ANS:- C 72. Defense mechanisms: A. Are adaptive coping mechanisms. B. Are neither adaptive or maladaptive but hinder adaptation. C. May be maladaptive or adaptive. D. Are maladaptive coping mechanisms. ANS:- C 73. Injury or illness is an example of: A. A long-term positive coping technique. B. A maladaptive coping behavior. C. A short-term positive coping technique. D. A stressor. ANS:- D 74. Which of the following is not one of the knowledge domains elaborated by Michael Leahy of Michigan State University in his 1992 national study? A. Case Management Concepts Factor B. Life Career Planning C. Physical and Psychosocial Aspects Factor D. Benefit Systems and Cost Benefit Analysis Factor ANS:- B 75. An individual sustaining a cervical neck injury: A. May possibly be rendered paraplegic, depending upon extent of injury. B. Will become a quadriplegic and may require a ventilator. C. Will become a paraplegic and lose function of the chest, abdomen, and other areas. D. May retain function of most areas, depending upon extent of injury. ANS:- B 76. Which is true of the Outcomes and Assessment Information Set (OASIS)? A. It represents the core items of a comprehensive assessment for adult home care. B. It is a forum for assessing the cost effectiveness of particular medications C. It was developed as a comprehensive assessment tool for quality of care D. It is a productivity quotient, assessing the productivity of any given group of healthcare workers in any given day ANS:- A 77. A form of hepatitis, producing infections only when HBV is present and exists at the expense of Hepatitis B, it's host, is named? A. Hepatitis D B. Hepatitis E C. Hepatitis C D. Hepatitis G ANS:- A 78. The purpose for using clinical level of care criteria as guidelines to support the case management process is so that: A) patients can be discharged as early as possible. B) patients can be treated at the most appropriate level of care as their condition changes. C) hospitals can profit from the DRG arrangement. D) physicians can follow the patients more efficiently from their offices rather than in the hospital. ANS:- B 79. The case manager's identification of potential problems or barriers to cost-effective, quality care begins : A) during the assessment phase. B) throughout the case management process. C) before discharge. D) after completion of the case selection process. ANS:- D 80. CPAP, continuous positive airway pressure, is most often utilized in the home for: A) ventilator dependent patients B) chronic obstructive lung disease. C) obstructive sleep apnea. D) cystic fibrosis. ANS:- C 81. A case manager is developing a plan for a client without an established support system, who is being discharged home from a skilled nursing facility, following a stroke. The knowledge area that will best assist the case manager during this phase of the case management process is: A) cost-benefit analysis. B) insurance principles. C) community resources and support programs. D) psychosocial aspects of chronic illness and disability. ANS:- C 82. It is important for the case manager to be aware of Medicare's definition of part-time or intermittent, when recommending ongoing services. Combined skilled nursing and home health aide services cannot total more than ____ hours per week. A) 20 B) 24 C) 28 D) 30 ANS:- C 83. A case manager is working with a client diagnosed with terminal metastatic cancer and in need of money to pay for medical care and living expenses. Selling a life insurance policy at 50-80% of its face value is: A) not a viable option. B) called a viatical settlement. C) an option frequently recommended by case managers. D) not ethical. ANS:- B 84. Best practices are predicted to do all the following EXCEPT: A) Improve clinical outcomes B) Increase health care costs C) Enhance administrative efficiency D) Increase patient satisfaction ANS:- B 85. Demand management, which provides risk appraisals, telephone health information services, and prevention and wellness initiatives, involves: A) a health professional contacting the client at prespecified intervals. B) the client calling an independent call center, a center set up by the health plan, or a number made available by the provider. C) the client initiating a call for emergency needs when the case manager is unavailable. D) None of the above ANS:- B 86. Upon meeting your client, a 40-year-old Asian woman, you note that throughout the assessment process she avoids eye contact. Your study of various cultural practices helps you understand that the behavior in this case is related to: A) embarrassment about her health problem. B) passivity. C) language barrier. D) a sign of deference. ANS:- D 89. The root cause of problems such as malnutrition, social isolation, alcohol abuse, and not adhering to treatment in the elderly population, is most frequently associated with: A) dementia. B) Alzheimer's disease. C) depression. D) endocrine imbalance. ANS:- C 90. The Glasgow Outcome Scale was commonly used prior to the development of the Rancho Los Amigos levels. Which of its five levels describes the stage where the client is able to follow commands but requires assistance for activities of daily living? A) Gross disability B) Severe disability C) Moderate disability D) Mild disability ANS:- B 91. The most appropriate objective for conducting a job analysis, which includes an in-depth review of the purpose of the job, related tasks, and the frequency of the tasks, in association with a disabled client in a return-to-work program, is to: A) evaluate whether a job description requires modifications. B) best match job functions, expectations or requirements, with abilities and limitations. C) determine when an individual should be promoted. D) comply with ADA (American Disabilities Act). ANS:- B 92. Which is the most appropriate strategy for promoting behavioral changes among adolescents with obesity? A. Age-matched, self-help group discussions B. Family-centered group discussions C. Individualized nutrition counseling D. Lectures on esteem enhancement ANS:- A 93. As a member of an interdisciplinary cardiac rehabilitation team, a nurse case manager's primary responsibility is to: A. communicate with families or significant others in meeting the client's care objectives. B. consult with health care professionals to coordinate resources and arrange referrals. C. coordinate with health insurance providers to formulate care plans and meet predetermined outcomes. D. document and disseminate assessment information from the team of health care professionals. ANS:- B 94. A child who is ventilator-dependent and has a gastrostomy button is scheduled to be discharged to home with visits from a home health nurse. Prior to discharge, the nurse case manager's most critical action is to: A. assess the child's long-term home care needs. B. procure the required home medical equipment. C. secure funding sources for home health care. D. verify that the child is being discharged to a safe environment. ANS:- D 95. Which type of authorization is generated when services are rendered? A. Concurrent B. Prospective C. Retrospective D. Subauthorization ANS:- A 96. Managing clinical outcomes, studying variance trends, and evaluating actions taken to correct deviations from critical pathways are components of: A. performance improvement. B. risk management. C. the nursing process. D. utilization review. ANS:- A 97. During an annual gynecologic examination, a 28-year-old female client with two small children requests a resupply of oral contraceptives. The patient confides that her husband is scheduled to be laid off next month and the family cannot afford health insurance. The nurse case manager's most appropriate intervention is to: A. ask the clinic business office to arrange special payment for the client. B. direct the client to the local Planned Parenthood clinic for her gynecologic and contraceptive needs. C. recommend that the client change her contraceptive method to condoms. D. refer the client to local social services agencies. ANS:- D 98. To avoid hospital readmission, a patient requires services at a specialty clinic. Since the services are not covered under the patient's health care plan, a nurse case manager intercedes with the patient's insurance company. In this situation, the nurse case manager is acting in the role of: A. broker. B. consultant. C. negotiator. D. provider. ANS:- C 99. When using a utilization tool to perform a concurrent review, a nurse case manager recognizes that: A. clients have a right to set length of stay without incurring nonreimbursable costs. B. discharge is required whenever the tool so indicates. C. exceptions exist because utilization tools reflect only average circumstances. D. the use of utilization tools guarantees payment for services. ANS:- C 100. Ideally, case management planning identifies goals that are: A. anticipated, acceptable, and appropriate. B. challenging and timely. C. patient-focused and cost-effective. D. realistic, measurable, and specific. ANS:- D CASE MANAGER Questions and answers pdf Download Read the full article

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Immunological Challenges to the Development of Chagasic Mega Syndromes-Juniper Publishers

Abstract

Chagas´ disease is one of the most serious parasitic diseases in Latin America, with a social and economic impact that far outweighs the combined effects of other parasitic diseases such as malaria, leishmaniasis and schistosomiasis. Chagas’ disease presents two well-defined phases, the acute phase and the chronic phase. The acute phase lasts for approximately two or three months. After this phase, the patient enters an asymptomatic state, which characterizes the beginning of the chronic phase. In the chronic phase of the disease, the destruction of components of the enteric nervous system leads to the development of megaesophagus and megacolon. Mega syndromes are characterized as dilatation of the organ associated with an inflammatory infiltrate that is the main responsible for the destruction of the enteric neurons. This review aims at organizing the data previously known about the challenges faced by the immune system in the presence of Chagas disease and the establishment of the chagasic megaesophagus and megacolon in an attempt to discover which is the key mechanism that defines the installation and the protection against the digestive form of this pathology.

Keywords: Chagas’ disease; Chagasic megacólon; Immune system

Introduction

The first suspicion of the existence of the digestive form of Chagas disease came in 1916, when Carlos Chagas himself observed that during the acute infection, some adults exhibited a marked dysphagia for foods whose ingestion needed to be accompanied by water. Patients reported that food transit was interrupted in the esophagus, causing immense pain. Even the ingestion of fluids could be difficult, being sometimes impossible, and in this way, the need for it to be administered in small doses. This phenomenon, without pathogenic explanation, was then termed “Mal do engasgo” [1]. The digestive forms of Chagas’ disease are present prominently in the regions below the equatorial line, with esophagopathy occurring in approximately 7 to 10% of cases and colopathy in 3 to 7%. The chagasic megacolon affects, above all, the sigmoid and the rectum. It may manifest as an isolated disease, but is often found associated with megaesophagus or Chagas’ heart disease. It is more common to adult (30 to 60 years) and more incident in the male sex. As the first symptom of mega colon is constipation, both the clinical and the anatomical diagnosis are usually late, after the establishment of the dilatation [2]. Optical light microscopy shows chronic, focal and diffuse inflammatory infiltrates in the muscularis of the mucosa, in the sub mucosa and in the muscular layers, lesions of the enteric nervous system, especially of the my enteric plexus, periganglionite and focal or diffuse gang lionitis with intense regressive phenomena of the neurons arriving at the complete destruction of the nervous ganglia of the my enteric plexus, with consecutive fibrosis, ulcerations and chronic inflammation of the mucosa, focal or diffuse in more advanced cases, reaching the sub mucosa, inter muscular interstitial fibrosis, focal or diffuse, due to myositis, periganglionitis and ganglionitis [3]. Ultra structural changes of my enteric plexus consist of lesions, usually focal, of all components of the ganglia: neurons, Schwann cells and nerve fibers. Therefore, it is common, in the same ganglion, the existence of neurons, sometimes deeply damaged alongside others morphologically intact. In severe cases, the lesion may be diffuse and the ganglion ends up being replaced by dense fibrous connective tissue [4]. It is permissible to admit a progression of the lesions of the plexus, which worsen proportionally to the duration and degree of the mega. The accumulation of feces in the colon causes light dilation and compression of the mucosa. Compression, in turn, leads to ischemia, and secondarily to degeneration, necrosis and ulceration of the mucosa. In the mucosa so ulcerated begins a secondary inflammatory process and independent of the inflammation induced by Chagas’ disease itself. This inflammatory process reaches my enteric plexus already previously damaged by T. cruzi, further aggravating the destruction of the enteric nervous system (SNE). In turn, the sub mucosal plexus suffers the consequences of the lesions of my enteric plexus, due to the synaptic relations between them. Inflammation secondary to stasis added to destruction of the plexus and interstitial components evolves into interstitial fibrosis of the sub mucosa and inter muscular conjunctiva. In turn, increasing the resistance of the medium requires more effort in the muscle fibers for contraction. Over time, hypertrophy and regressive changes in muscle fibers occur. The latter is consequence of disorders of metabolic changes of muscle cells and the interstitium induced by inflammation itself (vascular changes, edema, cellular infiltrate and fibrosis) that interposes between them. Because the sub mucosal plexus is closely related to muscle cells, it is easy to understand how myositis and its squeal can further damage the lymph nodes [5]. The scarcity of parasites in relation to the intensity and extent of the lesions in the chronic phase of the disease led several authors to evaluate the involvement in autoimmune factors of the pathogenesis of the chagasic lesion. Some authors point in the existence of a crossreaction between autologous components and T. cruzi antigens. Studies using an experimental infection model by T. cruzi suggest that during the acute phase of infection there would be a polyclonal activation responsible for the release of self-reactive clones that would persist for long periods in the host, leading to the appearance of lesions [6]. Although parasitism is scarce in relation to the intensity and extent of the lesions, several studies leave no doubt as to the presence of the parasite in the tissues of chagasic patients [7], found that the cardiac inflammatory process was particularly evident in parasitized muscle cells. Barbosa et al. [8] demonstrated, through autopsies of patients with diffuse chagasic myocarditis, the presence of T. cruzi amastigote forms into heart samples as well as extra-cardiac tissues. In the last decade, using polyclonal anti- T. cruzi to detect parasite antigens in heart tissues of patients with chagasic cardiopathy, Higuchi et al. [9] have shown a close correlation between the presence of parasite antigens and the intensity of the inflammatory infiltrates. Another methodology used is the polymerase chain reaction (PCR) technique, through which T. cruzi DNA is detected in inflammatory lesions in patients with Chagas’ and Chagas’ cardiomyopathy with megaesophagus [10,11].

The inflammatory process of the chronic phase of Chagas disease always shows signs of cellular activity. In the chagasic megaesophagus, inflammatory infiltrates are composed of 72- 93% of CD3-IR T lymphocytes, 6-29% of CD68-IR macrophages and 1-4% of CD20-IR B lymphocytes. About 1-35% of the inflammatory infiltrate cells in the muscle layers express TIA- 1 (T-cell intracellular antigen) a protein found in cytotoxic lymphocytes and Natural Killer cells. Natural Killer CD57- IR cells were rarely observed. These findings suggest that cytotoxic T lymphocytes may be involved in the pathogenesis of chagasic megaesophagus as well as in the development of heart disease present in some individuals with chronic infection [12]. Corbett et al. [13] analyzing tissues of chagasic patients with megacolon demonstrated the presence of Natural Killer cells, thus suggesting their participation in the continuation of the chronic phase inflammatory process of the megacolon of chagasic patients. Lemos et al. [14], studying patients with the digestive tract of Chagas disease, performed peripheral blood analysis of these individuals to verify the circulating lymphocyte phenotype. A significant decrease in the number of CD3/CD4- IR T lymphocytes and CD19-IR B lymphocytes was observed. The number of CD4-IR T lymphocytes / number of CD8-IR T lymphocytes was decreased from individuals with advanced megaesophagus, thus demonstrating a more significant decrease in the number of CD4-IR T lymphocytes, which is not observed in cardiac non-mega-chagasic patients [15]. As a marker for activation of T lymphocytes in mega-bearing patients, an anti- HLA-DR antibody was used and in this way elevated levels of activated T lymphocytes were demonstrated, which had already been observed in patients with Chagasic or even asymptomatic heart disease. Still in mega-bearing patients, there was also a decrease in the percentage of CD4/CD28-IR cells, which initially suggested that the lack of the CD28 co-stimulation molecule could in some way lead to failures of immune resistance mechanisms and contribute to progression of the disease. This hypothesis is in part corroborated by the studies of Miyahira et al. [16] that evaluated the role of the CD28-CD80/CD86 co-stimulation pathway to the resistance of mice to T cruzi infection. This study concluded that this pathway is essential for the organism to develop resistance to T cruzi, since the abolition of this pathway led to a decrease in the production of interferon and the activation of CD8-IR lymphocytes, resulting in an exacerbation of parasitemia.

Eosinophils are important cells in resistance to T. cruzi infection and their role in chronic phase pathology has been considered by several authors [17,18]. Eosinophils synthesizes and release several bioactive mediators and are important to both intestinal physiology and defense against various pathologies [19,20]. These cells have intra-cytoplasmic granules that may vary due to the degree of maturation and activation of the cell. These granules have four main substances: primary basic protein (MBP), cationic eosinophilic protein (ECP), eosinophil peroxidase (EPO) and eosinophil-derived neurotoxin (EDN). These proteins give the eosinophil a high capacity for cell destruction. For many years eosinophils have been believed to possess only pro-inflammatory action, but it is now known that these cells are also capable of secret immuno-mediators that may participate in the modulation of the inflammatory process. In the intestine, eosinophils are found mainly associated with observed lesions and acute and chronic inflammatory processes, and their role in defense against parasites is well known [21- 24], using mice infected with T cruzi, evaluated the kinetics of eosinophil release by bone marrow, suggesting a role as these cells in the parasite resistance process. Molina and Kierszenbaum performed a series of studies in which associations between eosinophils and the pathological changes induced by T. cruzi were demonstrated. In myocardial studies of chagasic patients, deposits of a neurotoxin derived from eosinophils in the myocardium of chagasic patients were observed, as well as the presence of activated eosinophils. A correlation between eosinophil concentration and severity of inflammatory lesions in the myocardium and skeletal muscles was also demonstrated. Later these same authors, using cultures of cardio my ocytes infected with T. cruzi, showed that eosinophils and neutrophils play an important role in the destruction of T. cruzi in myocardial cells [19,25,26].

Another cell of the immune system that plays an important role in the evolution of Chagas’ disease is the mast cell. Mast cells are multi-functional cells, being important both in intestinal physiology and in defense against pathological processes. These cells release pro inflammatory molecules, such as histamine and tumor necrosis factor alpha (TNF-α). Mast cells are also capable of increasing the permeability of the intestinal epithelium in situations of chronic stress, inflammatory processes and parasitic infections through mechanisms not yet known [27]. Mast cells function as the main link between the immune system and the enteric nervous system, detecting, encoding and transmitting information about these systems. Signals sent by mast cells in response to an invading agent act both on the immune system and on sensory neurons [22,28,29]. The evaluation of the role of mast cells in the pathology induced by T. cruzi infection has already been the subject of several studies. Almeida et al. [30], working with mice infected with T. cruzi, showed in the stomach of these animals a reduction of acetylcholine levels and an increase in histamine levels, probably due to the large number of mast cells in the gastric wall. Postan et al. [31] through in-vitro studies have suggested that the presence of mast cells is directly related to the development of fibrosis in cardiomyocytes infected by T. cruzi. Recently, Freitas et al. [28] demonstrated that the presence of serotonin is closely related to the concentration of mast cells in the colon of chagasic patients and that this would represent the main form of communication between the immune system and the enteric nervous system. This would represent a great possibility of pharmacological intervention in inflammatory bowel diseases where intestinal transit is compromised due to an intense inflammatory reaction.

Conclusion

We believe in the existence of an interconnection between the immune and neuro endocrine systems. This link would promote a bi-directional information exchange about the immune system and the enteric nervous system. Mast cell activation, besides performing roles in gastrointestinal physiology, plays a crucial role in the inflammatory process, being one of the main encoders of intestinal signs that will culminate in motor responses, visceral perceptions and activation of cells of the immune system in gastrointestinal pathologies.

Acknowledgement

This work was supported by funds from CNPq (Conselho Nacional de Desenvolvimento Científicoe Tecnológico) Grant 404718/2016-7, Brazil.

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