Biochemistry, Molecular Biology, Physiology, Microbiology, Immunology, Pharmacology & Drug Discovery
Preparation Lecture Notes, Multiple Choice Questions, Scientific Discoveries

Endocrinology: Thyroid Hormone Disorders and Function test

December 01, 2019

Thyroid Hormone Synthesis, Disorder, and Function Test- Multiple Choice Questions

1) Which of the following amino acid is the precursor for the synthesis of thyroid hormones?
a) Tryptophan
b) Tyrosine
c) Alanine
d) Proline

2) Which of the following form is the active form of thyroid hormone
a) T3
b) T4
c) rT3
d) None of the above

3) Which of the following proteins is the precursor for the thyroid hormone, and also a marker of thyroidal cancer?
a) Thyroalbumin
b) Thyroglobulin
c) Thyroid binding globulin
d) All of the above

4) The majority of the thyroid hormones in the blood are bound to proteins. Which of the following is not the thyroid hormone-binding proteins in the plasma?
a) Albumin
b) Thyroglobulin
c) Thyroid binding globulin
d) None of the above

5) Which of the following is the transporter responsible for the transport of iodine into the thyroid cells against the concentration gradient?
a) Na+ I- symport
b) K+ I- symport
c) I-/Cl- antiport
d) None of the above

6) Thyroperoxidase is an enzyme responsible for thyroid hormone synthesis. This enzyme catalyzes the following reaction except:
a) Conversion of iodide to iodine-free radical
b) Incorporation of iodine to a tyrosine residue of thyroglobulin
c) Condensation of monoiodotyrosine and diiodotyrosine
d) Cleavage and release of thyroid hormones

7) In addition to inhibiting thyroid hormone synthesis, which of the following chemical drug that also reduces the uptake of iodine into the thyroid cells?
a) Carbimazole
b) Methimazole
c) Thiourea
d) All of the above

8) The thyroid hormone synthesis is regulated by thyroid-stimulating hormone (TSH) synthesized by the anterior pituitary gland. The increased thyroid hormone synthesis is mediated by:
a) increased cGMP production in follicular cells
b) increased cAMP production in follicular cells
c) increased Ca+2 ions in the follicular cells
d) increased diacylglycerol production in follicular cells

9) Which of the following cellular processes increase in response to thyroid-stimulating hormones?
a) Uptake of iodide into the follicular cells
b) Synthesis of thyroglobulin proteins
c) Incorporation of iodide ions into tyrosine molecules of thyroglobulin
d) All of the above

10) The deiodinase are responsible for the removal of iodine from T4 molecules to produce T3 & rT3. Which of the type of the enzyme catalyzes the conversion of rT3?
a) Type I
b) Type II
c) Type III
d) None of the above

Answers
1-b) Tyrosine
2-a) T3
3-b) Thyroglobulin
4-b) Thyroglobulin
5-a) Na+ I- symport
6-d) Cleavage and release of thyroid hormones
7-a) Carbimazole
8-b) increased cAMP production in follicular cells
9-d) All of the above
10-c) Type III


Endocrinology: Thyroid Hormone Disorders and Function test Endocrinology: Thyroid Hormone Disorders and Function test Reviewed by Biotechnology on December 01, 2019 Rating: 5

Accurate Quantification and Characterization of Adeno-Associated Viral Vectors

November 04, 2019
In this original research article, Dobnik et al. used the molecular biology technique and the transmission electron microscopy technique to characterize and quantitate the viral vectors used for clinical trials.

Accurate Quantification and Characterization of Adeno-Associated Viral Vectors
David Dobni, et al 2019. Frontier in Microbiology

One of the main challenges in the gene therapy viral vector development is to establish an optimized process for its large scale production. This requires optimization for upstream and downstream processes as well as methods that enable the step-by step analytical characterization of the virus, the results of which inform the iterative refinement of production for yield, purity and potency. The biggest problem here is a plethora of viral vector formulations, many of which interfere with analytical techniques. We took adeno-associated virus (AAV) as an example and showed benefits of combined use of molecular methods and transmission electron microscopy (TEM) for viral vectors’ characterization and quantification. Results of the analyses showed that droplet digital PCR (ddPCR) performs better than quantitative real-time PCR (qPCR), in terms of robustness and assay variance, and this was especially relevant for partially purified (in-process) samples. Moreover, we demonstrate the importance of sample preparation prior to PCR analysis. We evaluated viral structure, presence of aggregates and impurities with TEM analysis and found that these impacted the differences in viral titers observed by qPCR and ddPCR and could be altered by sample preparation. These results serve as a guide for the establishment of the analytical methods required to provide measures of identity and purity for AAV viral vectors.

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Accurate Quantification and Characterization of Adeno-Associated Viral Vectors Accurate Quantification and Characterization of Adeno-Associated Viral Vectors Reviewed by Biotechnology on November 04, 2019 Rating: 5

Mitigation strategy for Unwanted Immunogenicity of Therapeutic Proteins

November 04, 2019
In this review article, Fontana et al. discuss the strategies for reducing immunogenicity for therapeutic proteins using various immunomodulatory regimens. These immunomodulatory strategies may reduce the deleterious effect of the immune response evoked against the therapeutic proteins, and improve the safety and efficacy of therapeutic proteins.
The strategies include agents that reduce B-cell proliferation, immune tolerization etc.

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development
Laura I. Salazar-Fontana et al. (AAPS 2017: 19(2):377-385)

Abstract
All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

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Mitigation strategy for Unwanted Immunogenicity of Therapeutic Proteins Mitigation strategy for Unwanted Immunogenicity of Therapeutic Proteins Reviewed by Biotechnology on November 04, 2019 Rating: 5

Taking immunogenicity assessment of therapeutic proteins to the next level

November 03, 2019
Taking immunogenicity assessment of therapeutic proteins to the next level
Büttel IC et al, Biologicals. 2011 Mar;39(2):100-9
Abstract
Therapeutic proteins provide innovative and effective therapies for numerous diseases. However, some of these products are associated with unwanted immunogenicity that may lead to clinical consequences such as reduced or loss of efficacy, altered pharmacokinetics (PK), general immune and hypersensitivity reactions, and neutralisation of the natural counterpart (e.g. the physiological hormone). Regulatory guidance on immunogenicity assessment needs to take into consideration a great diversity of products, indications and patient populations as well as constantly advancing manufacturing technologies. Such guidance needs to be sufficiently specific while, at the same time, allowing interactive discussion and adjusted benefit-risk weighing of each product on a case-by-case basis, e.g. for a unique treatment of a life threatening disease acceptable treatment risks may differ considerably from the ones in case of less serious disease. This theme was the focus of the international conference "Taking immunogenicity assessment of therapeutic proteins to the next level", held at the Paul-Ehrlich-Institut in Langen, Germany, on the 10-11. June 2010. The objectives of the conference were to highlight how the field could move from that of a mere description of risk factors to a system of risk assessment and mitigation, as well as an understanding of the impact of unwanted immunogenicity on the overall benefit/risk consideration for a medicinal product. More than 150 experts from industry, academia and regulatory authorities worldwide discussed the phenomenon of undesired immunogenicity from different perspectives. The conference focussed on issues relevant to three areas: (1) new European guidelines that are currently the subject of discussion; (2) testing strategies for immunogenicity assessment; and (3) scientific progress on the product-related factors that may contribute to the development of pathogenesis of immunogenicity, in particular in the field of protein aggregation and post-translational modifications. This report provides an overview of issues, insights, and conclusions that were discussed and achieved during the meeting.



Taking immunogenicity assessment of therapeutic proteins to the next level Taking immunogenicity assessment of therapeutic proteins to the next level Reviewed by Biotechnology on November 03, 2019 Rating: 5

Immunogenicity of biotherapeutics for biosimilars and biobetters.

November 03, 2019
Immunogenicity of biotherapeutics in the context of developing biosimilars and biobetters. 

Barbosa MD. Drug Discov Today. 2011 Apr;16(7-8):345-53.

Abstract
Issues concerning the approval of biosimilars are currently being addressed by the US Food and Drug Administration and the European Medicines Agency. There appears to be a consensus that immunogenicity impacts comparability studies and the interchangeability of biosimilars. In addition, preclinical immunogenicity assessment and mitigation, if validated in clinical studies, might impact patient safety and development costs, and also facilitate the development of 'biobetters' and other protein therapeutics. This review addresses recent advances in the field of biosimilars and focuses on predictive immunology, with an emphasis on preclinical immunogenicity assessments of protein therapeutics other than vaccines and their corresponding clinical outcomes.



Immunogenicity of biotherapeutics for biosimilars and biobetters. Immunogenicity of biotherapeutics for biosimilars and biobetters. Reviewed by Biotechnology on November 03, 2019 Rating: 5

Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility.

November 03, 2019
Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility.

Wadhwa M, Knezevic I, Kang HN, Thorpe R. Biologicals. 2015 Sep;43(5):298-306.  

Biotherapeutic products (BTPs) are the fastest growing medicines in the pharmaceutical market. Despite their clinical success, the immunogenicity of BTPs continues to be a major concern. Assessment of immunogenicity as well as appropriate interpretation of immunogenicity data is therefore, of critical importance for defining safety profile of these products for the purpose of their licensure and use. In the past decade, much progress has been made towards how immunogenicity should be studied. This article reflects the content of the brief presentation on principles of methods used for immunogenicity assessment and their merits and limitations given at the first World Health Organization (WHO) implementation workshop on rDNA derived biotherapeutic products held in the Republic of Korea in May 2014 to support the case studies on immunogenicity presented and discussed during the workshop. The purpose of this article is to provide an overview of the methods used for assessing immunogenicity of biotherapeutic products (BTPs) and the most important considerations in interpreting results in the context of a regulatory overview of these products.




Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility. Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility. Reviewed by Biotechnology on November 03, 2019 Rating: 5

Characterization of immunogenicity response to multiple domain biotherapeutics

November 03, 2019
Recommendations for the characterization of immunogenicity response to multiple domain biotherapeutics.
Gorovits B, Wakshull E, Pillutla R, Xu Y, Manning MS, Goyal J
J Immunol Methods. 2014 Jun;408:1-12
Abstract
Many biotherapeutics currently in development have complex mechanisms of action and contain more than one domain, each with a specific role or function. Examples include antibody-drug conjugates (ADC), PEGylated, fusion proteins and bi-specific antibodies. As with any biotherapeutic molecule, a multi-domain biotherapeutic (MDB) can elicit immune responses resulting in the production of specific anti-drug antibodies (ADA) when administered to patients. As it is beneficial to align industry standards for evaluating immunogenicity of MDBs, this paper highlights pertinent immunogenicity risk factors and describes steps involved in the design of a testing strategy to detect and characterize binding (non-neutralizing and neutralizing, NAb) ADAs. In a common tier based approach, samples identified as ADA screen positive are confirmed for the binding specificity of the antibodies to the drug molecule via a confirmatory assay. The confirmation of specificity is generally considered as a critical step of the tier based approach in overall ADA response evaluation. Further characterization of domain specificity of polyclonal anti-MDB ADA response may be required based on the analysis of molecule specific risk factors. A risk based approach in evaluating the presence of NAbs for MDB is discussed in this article. Analysis of domain-specific neutralizing antibody reactivity should be based on the risk assessment as well as the information learned during binding ADA evaluation. Situations where additional characterization of NAb specificity is possible and justified are discussed. Case studies demonstrating the applicability of the risk factor-based approach are presented. In general, the presence of a domain with high immunogenicity risk or presence of a domain with high endogenous protein homology may result in an overall high immunogenicity risk level for the entire MDB and can benefit from domain specificity characterization of immune response. For low immunogenicity risk MDBs, domain specificity characterization could be re-considered at later clinical phases based on the need to explain specific clinical observations. Inclusion of domain specificity characterization in early phase clinical studies for MDBs with limited clinical immunogenicity experience may be considered to help understand its value in later clinical development. It is beneficial and is recommended to have a well-defined plan for the characterization of ADA domain specificity and data analysis prior to the initiation of sample testing. Overall, best practices for immunogenicity evaluation of complex MDBs are discussed.

Characterization of immunogenicity response to multiple domain biotherapeutics Characterization of immunogenicity response to multiple domain biotherapeutics Reviewed by Biotechnology on November 03, 2019 Rating: 5

Recommendation for risk-based bioanalytical strategy for the immunogenicity assessment for biologics

November 03, 2019
A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs. 

Shankar G, Pendley C, Stein KE. Nat Biotechnol. 2007 May;25(5):555-61.

Bioanalytical assessments of anti-drug antibodies (ADAs) provide an understanding
of the immunogenicity of biological drug molecules. The potential to induce ADAs after treatment with biologics is a safety issue that has become an important consideration in the development of biologics and a critical aspect of regulatory filings. US and European regulatory agencies are recommending that sponsors study immunogenicity using a risk-based approach, encouraging sponsors to formulate and implement their own risk management plans and to conduct discussions with the agencies when necessary. It follows from this that the greater the safety risks of ADAs, the more diligently one should clarify the immunogenicity of the product. Here we propose a general strategy to broadly assign immunogenicity risk levels to biological drug products, and present risk level-based 'fit-for-purpose' bioanalytical schemes for the investigations of treatment-related ADAs in clinical and nonclinical studies.

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Recommendation for risk-based bioanalytical strategy for the immunogenicity assessment for biologics Recommendation for risk-based bioanalytical strategy for the immunogenicity assessment for biologics Reviewed by Biotechnology on November 03, 2019 Rating: 5

Pharmacokinetics-Pharmacodynamics/clinical response modeling and simulation for biologics

November 03, 2019
In this review article, Zhao et al. discuss the guiding principle and the core mathematical modeling underlying PK or PK-PD model used.

Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development. 
Zhao L, Shang EY, Sahajwalla CG. 
J Pharm Sci. 2012 Dec;101(12):4367-82

Biologics, specifically monoclonal antibody (mAb) drugs, have unique pharmacokinetic (PK) and pharmacodynamic (PD) characteristics as opposed to small molecules. Under the paradigm of model-based drug development, PK-PD/clinical response models offer critical insight in guiding biologics development at various stages. On the basis of the molecular structure and corresponding properties of biologics, typical mechanism-based [target-mediated drug disposition (TMDD)], physiologically based PK, PK-PD, and dose-response meta-analysis models are summarized. Examples of using TMDD, PK-PD, and meta-analysis in helping starting dose determination in first-in-human studies and dosing regimen optimization in phase II/III trials are discussed. Instead of covering the entirety of model-based biologics development, this review focuses on the guiding principles and the core mathematical descriptions underlying the PK or PK-PD models most used.




Pharmacokinetics-Pharmacodynamics/clinical response modeling and simulation for biologics Pharmacokinetics-Pharmacodynamics/clinical response modeling and simulation for biologics Reviewed by Biotechnology on November 03, 2019 Rating: 5

Medical Microbiology: Vector Borne Viruses

November 01, 2019
Multiple Choice Question on 
Vector-Borne Viruses

1) Which of the following is not the mosquito-borne viral disease?
a) Dengue
b) Lassa fever
c) Yellow fever
d) Japanese B encephalitis

2) Name the vector via which viruses causing encephalitis and yellow fever is transmitted to humans?
a) Ticks
b) Sandflies
c) Mosquitoes
d) Rodents

3) All of the following statements are true regarding Arboviruses, Except?
a) All viruses of the family have a single-stranded RNA genome
b) They cause arthropod-borne viral infections
c) Viruses only belong to the family Arenaviridae
d) They can infect humans, animals, and plants


4) Japanese B encephalitis has been mainly found in Asia transmitted through the bite of a mosquito, which of the following is the reservoir of the virus?
a) Herons
b) Horses
c) Cows
d) Rabbits

5) Name the Arbovirus that does not cause hemorrhagic fever in humans?
a) Lassa fever virus
b) Yellow fever virus
c) Hantavirus
d) Marburg and Ebola virus

6) The viruses belonging to the Bunyaviridae family can cause infections in humans which is transmitted via arthropods or rodents, select all the correct statements regarding the virus.
a) Consists of the virus that cause Encephalitis and hemorrhagic fever
b) Hantavirus belongs to the family
c) Yellow fever is the most common infection
d) The virus causing Rift valley fever is transmitted from animals to humans

7) Which of the following statement is true regarding the West Nile virus?
a) Humans get infected with the virus from the tick bite
b) The virus causes severe hemorrhagic fever
c) Belongs to the genus Flavivirus
d) The virus spreads from person to person

8) A 19 years old boy from Delhi, India suddenly develops a high fever with a headache, stomach ache, vomiting, muscle pain, and diarrhea, when examined dengue fever is diagnosed. Dengue is developed after the bite of mosquito bite infected with the virus, which of the following statement is not correct about the dengue virus?
a) Belongs to the Togaviridae family
b) Mostly found in tropical and subtropical regions of the world
c) More than one antigenic type of virus is present
d) A person can develop severe hemorrhagic fever

9) All of the following statements are true about rodent-borne viral infections, Except?
a) Caused by bunyaviruses and arenaviruses
b) Hantavirus infections and Lassa fever are major rodent-borne viral infections
c) Human to human transmission is possible
d) None of the above


10) Which of the following statement is True regarding the transmission of the virus causing Lassa fever?
a) It is transmitted to humans through the ticks
b) The virus is prevalent in Asian countries
c) Person to person transmission does not occur
d) The drug ribavirin has found to be effective against the virus

11) Yellow fever is caused by a flavivirus, the person infected develops jaundice with back pain and headache, in severe condition bleeding from nose and mouth. Which of the following statement is not correct about yellow fever?
a) Mostly occur in the tropical and subtropical area of Africa and South America
b) Ticks are the major vector of the virus
c) Presented with necrotic lesions in the liver and kidney
d) An attenuated vaccine is available

12) All of the following statements regarding Hantavirus pulmonary syndrome is true, Except?
a) Flu-like symptoms that can result in life-threatening respiratory infection
b) No vaccine or any antiviral drug is available for the virus
c) The virus is only carried by deer mice
d) None of the above

13) Ebola virus causes hemorrhagic fever in humans and is often fatal, all of the following are the characteristics of the infection caused by the virus, Except?
a) Person to person transmission is possible
b) The vaccine is available for the virus
c) It is highly virulent in humans and nonhuman primates
d) The virus belongs to the family Flaviviridae

14) Japanese B encephalitis, dengue and West Nile fever all belong to the genus Flavivirus?
a) True
b) False


15) Chikungunya virus infection has been spreading throughout America in recent years, the virus is transmitted to humans via mosquito bite. Which of the following are the major symptoms of this infection?
a) Severe leg and arm joints pain
b) Influenza-like symptoms
c) Yellowing of the skin
d) Bleeding from the nose

Answers
1-b) Lassa fever
2-c) Mosquitoes
3-a) All viruses of the family have a single-stranded RNA genome
4-a) Herons
5)-
6-a), b) & d)
7-c) Belongs to the genus Flavivirus
8-a) Belongs to the Togaviridae family
9-d) None of the above
10-d) The drug ribavirin has found to be effective against the virus
11-b) Ticks are the major vector of the virus
12-d) None of the above
13-d) The virus belongs to the family Flaviviridae
14-a) True
15-a) Severe leg and arm joints pain



Medical Microbiology: Vector Borne Viruses Medical Microbiology: Vector Borne Viruses Reviewed by Biotechnology on November 01, 2019 Rating: 5

Medical Microbiology: MCQ on Mumps, Meseales and Rubella virues

October 17, 2019
Multiple Choice Question on Mumps, Meseales and Rubella

1) Paramyxoviruses have all of the following properties, EXCEPT?
a) Consists of a segmented genome
b) Envelope contains of glycoprotein which has fusion activity
c) Has a negative RNA genome
d) Replicate in the cytoplasm

2)  Each of the following pathogens causes respiratory infections in humans, EXCEPT?
a) Respiratory syncytial virus
b) Parainfluenza virus
c) Measles virus
d) Rabies virus

3) Respiratory syncytial virus mainly infect the lower respiratory tract of the lungs causing bronchiolitis and pneumonia mainly in children and elderly people, which of the following virus is not commonly found in the lower respiratory tract infection?
a) Rhinovirus
b) Metapneumovirus
c) Influenza virus
d) Respiratory syncytial virus

4) Which of the following is an example of the natural hosts of Mumps virus?
a) Pigs
b) Bats
c) Horses
d) Humans

5) Measles virus are transmitted through airborne droplets, and is one of the leading causes of respiratory infections mostly seen in children of developing countries. Which of the following statements is Not correct about the epidemiologic features of measles?
a) More than one serotypes of the virus has been identified
b) Humans are the only reservoir
c) Infection confers lifelong immunity
d) The virus can be transmitted from infected mother to the fetus

6) Mumps is a highly contagious viral infection transmitted from person to person, which of the following is not the symptoms of the mumps virus?
a) Fever
b) Muscle aches
c) Swollen salivary glands
d) Skin rashes

7) All of the following statements about measles (Rubeola) and rubella (German measles) are true, EXCEPT?
a) Humans are the only host for the rubella virus
b) Rubella virus specifically invades respiratory system
c) Rubeola virus infection is characterized by maculopapular rashes
d) Rubella can cause serious birth defects

8) Which of the following age group is mostly affected by parainfluenza virus?
a) Teenagers
b) Babies >
c) Elder people
d) School-age children

9) Which of the following statements is correct about congenital rubella syndrome?
a) Child born to a mother who were not vaccinated previously are at higher risks
b) If infected the newborn are present have usually mild infections
c) Ribavirin is very effective drug for the treatment of the infection
d) All of the above

10) After the measles virus enters the host cells and multiplies, the person develops skin rashes within 2 to 5 days after the infection, which of the following is Not the common symptoms related to measles?
a) Red and watery eyes
b) Runny nose
c) High grade fever
d) Enlarged salivary glands

11) Each of the following statements about measles vaccine is correct, EXCEPT?
a) The vaccine was first introduced in 1963
b) It is available only in a monovalent form
c) The vaccine is given only after 15 months of age because of the presence of maternal antibodies which prevents an immune response
d) The vaccine contains live, attenuated virus

12) Mumps virus can infect which of the following organs? Choose the correct answer from options given below
a) Salivary glands
b) Ovaries
c) Pancreas
d) Testes

13) The rubella vaccine consists of an inactivated rubella virus:
a) True
b) False

14) Which of the following statements is true about Reverse transcriptase polymerase chain reaction (RT-PCR)?
a) Very useful for mRNA quantitation
b) Highly specific assay than serology for certain virus detection
c) Low cost and easily available
d) Helps in the identification of virus strains

15) The vaccine is available for all of the following, EXCEPT?
a) Measles virus
b) Mumps virus
c) Human parainfluenza virus
d) Varicella-zoster virus

Answers
1-a) Consists of a segmented genome
2-d) Rabies virus 
3-a) Rhinovirus 
4-d) Humans
5-a) More than one serotypes of the virus has been identified 
6-d) Skin rashes 
7-b) Rubella virus specifically invades respiratory system 
8-b) Babies
9-a) Child born to a mother who was not vaccinated previously are at higher risks 
10-d) Enlarged salivary glands 
11-b) It is available only in a monovalent form 
12- Option a), b), c), d
13-b) False
14-c) Low cost and easily available
15-c) Human parainfluenza virus


Medical Microbiology: MCQ on Mumps, Meseales and Rubella virues Medical Microbiology: MCQ on Mumps, Meseales and Rubella virues Reviewed by Biotechnology on October 17, 2019 Rating: 5

Medical Microbiology: Influenza Virus Type A, B & C

September 24, 2019

Influenza Virus Type A, B, & C
Multiple Choice Questions

1) Which of the following statement is NOT true about the influenza viruses A, B, and C?
a) Influenza type A can be found in chickens, pigs, and horses
b) Antigenic shifts or viral genome reassortment occurs in Influenza A virus, the common cause for worldwide epidemics
c) All three types of viruses are found in humans as well as animals
d) Influenza virus infects mainly the upper respiratory tract

2)The properties of Orthomyxoviruses include all of the following statement, EXCEPT?
a) The virus consists of single-stranded RNA
b) The outer envelope of the virus is made up of lipid bilayer
c) The size of the virus (150nm) is larger than the Paramyxoviruses >
d) The hemagglutinin and neuraminidase of the influenza virus helps it to attach to the host cells

3) Which of the following is NOT the common symptoms of flu caused by influenza virus in adults?
a) Fever
b) Cough
c) Rashes
d) Headache

4) Which of the following viruses gives lifelong immunity to disease............?
a) Rhinovirus
b) Influenza A virus
c) Influenza C virus
d) Measles virus

5) Which of the following immunologic types of influenza causes most of the epidemics?
a) Type A
b) Type B
c) Type C
d) None of the above

6) Which of the following are at risk of getting influenza flu? Choose the correct answer
a) A 70-year-old woman
b) A healthy 4-year-old boy
c) A 35-year-old man with diabetes
d) All of the above

7) The most common route of the pathogenesis of influenza virus is airborne droplets, which of the following virus is most likely to cause a pandemic?
a) Influenza A
b) Rhinovirus
c) Influenza B
d) All of the above

8) Which of the following microorganism is commonly associated with pneumonia caused by the influenza virus?
a) Rhinovirus
b) Staphylococcus aureus
c) Rubella virus
d) Chlamydia pneumoniae

9) All of the following statements are correct about the Neuraminidase (NA) and Hemagglutinin (HA) of influenza virus, EXCEPT?
a) Helps the virus to bind to host cell surface
b) Both of the antigens are embedded in the outer surface of the viral envelope
c) Neuraminidase is present as a spike and is composed of dimers
d) Frequent antigenic changes occur in NA and HA

10) A 16-year-old girl comes to the clinic with a sore throat, fever, and headache, the symptoms resembled the flu-like syndrome. Which of the following could be the primary sample/specimen for the laboratory diagnosis of influenza virus?
a) Blood
b) Sputum
c) Urine
d) Nasopharyngeal washing

11) Which of the following statements about isolation and identification of influenza is NOT correct?
a) The specimen should be kept at 4 degree Celsius
b) Culture of the virus is usually done by using embryonated eggs
c) The specimens should be taken within 1 to 3 days after the onset of symptoms
d) Rapid antigen detection tests cannot be done

12) Major antigenic changes in HA or NA is known as an antigenic shift which results in a new influenza virus subtype, True or False?
a) True
b) False

13)Which of the following is a reservoir for the antigenic shift variants of influenza virus?
a) Pigs and horses
b) Rodents
c) Mosquitoes
d) Human

14) Which of the following statement is NOT correct about the preventive measures of influenza virus?
a) Washing hands more often helps
b) A sick person with flu should stay isolated at least for 24 hours
c) Over the counter, antiviral drugs are available for influenza virus
d) Live attenuated and inactivated virus both are used for vaccination

15) What is the source of H5N1 infection in humans?
a) Birds
b) Pigs
c) Ferrets
d) None of the above

 Answers

1-c) All three types of viruses are found in humans as well as animals
2-c) The size of the virus (150nm) is larger than the Paramyxoviruses
3-c) Rashes
4-d) Measles virus
5-a) Type A
6-d) All of the above
7-a) Influenza A
8-b) Staphylococcus aureus
9-c) Neuraminidase is present as a spike and is composed of dimers
10-d) Nasopharyngeal washing
11-d) Rapid antigen detection tests cannot be done
12-a) True
13-a) Pigs and horses
14-c) Over the counter antiviral drugs are available for influenza virus
15-a) Birds

Medical Microbiology: Influenza Virus Type A, B & C Medical Microbiology: Influenza Virus Type A, B & C Reviewed by Biotechnology on September 24, 2019 Rating: 5

Antisense Oligonucleotide Volanesoren lowers triglyceride levels in Familial Chylomicronemia Syndrome

September 18, 2019
Witztum et al. recently published (New England Journal of Medicine, 2019) results from phase 3 clinical trials on efficacy and safety of antisense oligonucleotide Volanesoren in treatment of Familial Chylomicronemia. Familial Chylomicronemia is a genetic disorder caused by mutation of enzyme lipoprotein lipase, or associated proteins require for its function. Valonesoren inhibits the synthesis of ApoC-III, thereby decreasing the triglycerides level in patients with hypertriglyceridemia. Based on this clinical study, IONIS pharmaceutical obtained a positive opinion and conditional approval to market the product in the European Union region. ( Committee for Medicinal Products for Human Use- CHMP  Public Assessment Report ). The following are the excerpts and the result summary from the study:

Witztum et al, 2019, NEJM
Journal: New England Journal of Medicine
Title: Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome.
Abstract
BACKGROUND:
Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels.
METHODS:
We conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome. Patients were randomly assigned, in a 1:1 ratio, to receive volanesorsen or placebo. The primary end point was the percentage change in fasting triglyceride levels from baseline to 3 months.
RESULTS:
Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase (P<0.001). Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval [CI], 1330 to 2094 mg per deciliter [15.0 to 23.6 mmol per liter]), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, -301.0 to 486 mg per deciliter [-3.4 to 5.5 mmol per liter]) (P<0.001). At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter). A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions. No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter. No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began.
CONCLUSIONS:
Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection-site reactions were common adverse events.

Antisense Oligonucleotide Volanesoren lowers triglyceride levels in Familial Chylomicronemia Syndrome Antisense Oligonucleotide Volanesoren lowers triglyceride levels in Familial Chylomicronemia Syndrome Reviewed by Biotechnology on September 18, 2019 Rating: 5

Correlation of anti-AAV9 Preexisting antibody with In Vivo Transduction and NAGLU activity

September 17, 2019
Meadows et al. recently published papers (Mol Ther Methods Clin Dev, 2019) that investigated the threshold of antibody titer levels that would limit the transduction efficiency of systematic rAAV9 gene delivery.  The early clinical trials have revealed a potential impact of preexisting antibodies against adeno associated virus in the efficacy of transgene expressions. This study attempts to characterize the correlation of transgene expression (NAGLU)  with preexisting antibody titers against AAV9.  The nonclinical nonhuman primate studies were conducted to evaluate the transduction efficiency after systemic delivery of rAAV9 at varying level of preexisting antibodies and define efficacy threshold if any. The following are the excerpts and the result summary from the study:

Journal Title: Molecular Therapy: Methods & Clinical Development
Title:
Threshold for Pre-existing Antibody Levels Limiting Transduction Efficiency of Systemic rAAV9 Gene Delivery: Relevance for Translation
Abstract:
Widespread anti-AAV antibodies (Abs) in humans pose a critical challenge for the translation of AAV gene therapies, limiting patient eligibility. In this study, non-human primates (NHPs) with pre-existing αAAV Abs were used to investigate the impact of αAAV9 Ab levels on the transduction efficiency of rAAV9 via systemic delivery. No significant differences were observed in vector genome (vg) biodistribution in animals with ≤1:400 total serum αAAV9-IgG compared to αAAV9-Ab-negative animals, following an intravenous (i.v.) rAAV9-hNAGLUop (codon-optimized human α-N-acetylglucosaminidase coding sequence cDNA) injection. Serum αAAV9-IgG at >1:400 resulted in a >200-fold decrease in vg in the liver, but had no significant effect on vg levels in the brain and most of the peripheral tissues. Although tissue NAGLU activities declined significantly, they remained above endogenous levels. Notably, there were higher vg copies but lower NAGLU activity in the spleen in NHPs with >1:400 αAAV9 Abs than in those with ≤1:400 Abs. We demonstrate here the presence of a threshold of pre-existing αAAV9 Abs for diminishing the transduction of i.v.-delivered AAV vectors, supporting the expansion of patient eligibility for systemic rAAV treatments. Our data also indicate that high pre-existing αAAV9 Abs may promote phagocytosis and that phagocytized vectors are not processed for transgene expression, suggesting that effectively suppressing innate immunity may have positive impacts on transduction efficiency in individuals with high Ab titers.

Correlation of anti-AAV9 Preexisting antibody with In Vivo Transduction and NAGLU activity Correlation of anti-AAV9 Preexisting antibody with In Vivo Transduction and NAGLU activity Reviewed by Biotechnology on September 17, 2019 Rating: 5

Nonclinical Non-human Primate Studies for Hemophilia investigate impact of preexisting antibodies against AAV5 on therapeutic efficacy

September 17, 2019
Long et al. & Majowicz et al. recently published papers (Mol Ther Methods Clin Dev, 2019) that reported potential impact of preexisting antibodies against adeno associated virus serotype 5 ( AAV5) in the efficacy of transgene expressions. These nonclinical nonhuman primate studies were conducted to evaluate the efficacy of the gene therapy at varying level of preexisting antibodies. Factor VIII and factor IX activity as measured as a pharmacodynamic marker of efficacy.  The Following are the excerpts and the result summary from the study:

Journal: Molecular Therapy Methods & Clinical Development
Title: The Impact of Pre-existing Immunity on the Non-clinical Pharmacodynamics of AAV5-Based Gene Therapy
Abstract
Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit AAV vector transduction where antibodies are not detected. To better define the relationship between various forms of pre-existing AAV immunity and gene transfer, we studied valoctocogene roxaparvovec (BMN 270) in cynomolgus monkeys with varying pre-dose levels of neutralizing anti-AAV antibodies and non-antibody transduction inhibitors. BMN 270 is an AAV5-based vector for treating hemophilia A that encodes human B domain-deleted factor VIII (FVIII-SQ). After infusion of BMN 270 (6.0 × 1013 vg/kg) into animals with pre-existing anti-AAV5 antibodies, there was a mean decrease in maximal FVIII-SQ plasma concentration (Cmax) and AUC of 74.8% and 66.9%, respectively, compared with non-immune control animals, and vector genomes in the liver were reduced. In contrast, animals with only non-antibody transduction inhibitors showed FVIII-SQ plasma concentrations and liver vector copies comparable with those of controls. These results demonstrate that animals without AAV5 antibodies are likely responders to AAV5 gene therapy, regardless of other inhibiting plasma factors. The biological threshold for tolerable AAV5 antibody levels varied between individual animals and should be evaluated further in clinical studies.

Journal: Molecular Therapy Methods & Clinical Development
Title: Therapeutic hFIX Activity Achieved after Single AAV5-hFIX Treatment in Hemophilia B Patients and NHPs with Pre-existing Anti-AAV5 NABs
AbstractCurrently, individuals with pre-existing neutralizing antibodies (NABs) against adeno-associated virus (AAV) above titer of 5 are excluded from systemic AAV-based clinical trials. In this study we explored the impact of pre-existing anti-AAV5 NABs on the efficacy of AAV5-based gene therapy. AMT-060 (AAV5-human FIX) was evaluated in 10 adults with hemophilia B who tested negative for pre-existing anti-AAV5 NABs using a GFP-based assay. In this study, using a more sensitive luciferase-based assay, we show that 3 of those 10 patients tested positive for anti-AAV5 NABs. However, no relationship was observed between the presence of pre-treatment anti-AAV5 NABs and the therapeutic efficacy of AMT-060. Further studies in non-human primates (NHPs) showed that AAV5 transduction efficacy was similar following AMT-060 treatment, irrespective of the pre-existing anti-AAV5 NABs titers. We show that the therapeutic efficacy of AAV5-mediated gene therapy was achieved in humans with pre-existing anti-AAV5 NABs titers up to 340. Whereas in NHPs circulating human factor IX (hFIX) protein was achieved, at a level therapeutic in humans, with pre-existing anti-AAV5 NABs up to 1030. Based on those results, no patients were excluded from the AMT-061 (AAV5-hFIX-Padua) phase IIb clinical trial (n = 3). All three subjects presented pre-existing anti-AAV5 NABs, yet had therapeutic hFIX activity after AMT-061 administration.

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Nonclinical Non-human Primate Studies for Hemophilia investigate impact of preexisting antibodies against AAV5 on therapeutic efficacy Nonclinical Non-human Primate Studies for Hemophilia investigate impact of preexisting antibodies against AAV5 on therapeutic efficacy Reviewed by Biotechnology on September 17, 2019 Rating: 5

Industry trends on use of surrogate biomaker as endpoint for clinical benefit

September 17, 2019
Bruce et al. recently published a paper (PLOS Medicine, 2019) that provides a trend on the use of surrogate biomarkers to evaluate clinical benefits. The study primarily reviewed European Public Assessment Reports (EPARs) to identify the use of surrogate biomarkers for the primary endpoint.  The Following are the excerpts and the result summary from the study:

Journal: PLOS Medicine
Abstract
BACKGROUND:
 In situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorization (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorization recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorization remains conditional until regulator-imposed confirmatory postmarketing measures are fulfilled. For products undergoing AA, complete safety and efficacy data should be available, and post-authorization measures may include only standard requirements of risk management and pharmacovigilance plans. In the pivotal trials supporting products assessed by expedited pathways, surrogate endpoints reduce drug development time compared with waiting for the intended clinical outcomes. Whether surrogate endpoints supporting products authorized through CMA and AA pathways reliably predict clinical benefits of therapy has not been studied systematically. Our objectives were to determine the extent to which surrogate endpoints are used and to assess whether their validity had been confirmed according to published hierarchies. 
METHODS AND FINDINGS: 
We used European Public Assessment Reports (EPARs) to identify the primary endpoints in the pivotal trials supporting products authorized through CMA or AA pathways during January 1, 2011, to December 31, 2018. We excluded products that were vaccines, topical, reversal, or bleeding prophylactic agents or withdrawn within the study time frame. Where pivotal trials reported surrogate endpoints, we conducted PubMed searches for evidence of validity for predicting clinical outcomes. We used 2 published hierarchies to assess validity level. Surrogates with randomized controlled trials supporting the surrogate-clinical outcome relationship were rated as 'validated'. Fifty-one products met the inclusion criteria; 26 underwent CMAs, and 25 underwent AAs. Overall, 26 products were for oncology indications, 10 for infections, 8 for genetic disorders, and 7 for other systems disorders. Five products (10%), all AAs, were authorized based on pivotal trials reporting clinical outcomes, and 46 (90%) were authorised based on surrogate endpoints. No studies were identified that validated the surrogate endpoints. Among a total of 49 products with surrogate endpoints reported, most were rated according to the published hierarchies as being 'reasonably likely' (n = 30; 61%) or of having 'biological plausibility' (n = 46; 94%) to predict clinical outcomes. EPARs did not consistently explain the nature of the pivotal trial endpoints supporting authorizations, whether surrogate endpoints were validated or not, or describe the endpoints to be reported in the confirmatory postmarketing studies. Our study has limitations: we may have overlooked relevant validation studies; the findings apply to 2 expedited pathways and may not be generalizable to products authorized through the standard assessment pathway. 
CONCLUSIONS: 
The pivotal trial evidence supporting marketing authorizations for products granted CMA or AA was based dominantly on nonvalidated surrogate endpoints. EPARs and summary product characteristic documents, including patient information leaflets, need to state consistently the nature and limitations of endpoints in pivotal trials supporting expedited authorizations so that prescribers and patients appreciate shortcomings in the evidence about actual clinical benefit. For products supported by nonvalidated surrogate endpoints, post-authorization measures to confirm clinical benefit need to be imposed by the regulator on the marketing authorization holders.


Industry trends on use of surrogate biomaker as endpoint for clinical benefit Industry trends on use of surrogate biomaker as endpoint for clinical benefit Reviewed by Biotechnology on September 17, 2019 Rating: 5

Suitability of In vitro Neutralizing Antibody Assay to Detect low antibody titers against AAV

September 17, 2019
Kruzik et al. recently published a paper (Human Gene Therapy Methods, 2019) that provides the rationale for use of in vitro assay for the detection of low titer neutralizing antibody against adeno associated virus. The study showed superior sensitivity of in vitro NAb assay compared to the in vivo assay. Following are the excerpts from the study.

Journal: Human Gene Therapy Methods
Title: Detection of Biologically Relevant Low-Titer Neutralizing Antibodies Against Adeno-Associated Virus Require Sensitive In Vitro Assays
Abstract
"Patients with preexisting anti-adeno-associated virus serotype 8 (AAV8) neutralizing antibodies (NAbs) are currently excluded from AAV8 gene therapy trials. Therefore, the assessment of biologically relevant AAV8-NAb titers is critical for product development in gene therapy. However, standardized assays have not been routinely used to determine anti-AAV8-NAb titers, contributing to a wide range of reported anti-AAV8 prevalence rates. Using a clinical in vitro NAb assay in a separate study, a higher than the expected anti-AAV8-NAb prevalence of about 50% was found in international cohorts. This comparative study has a translational character, confirming the biological relevance of anti-AAV8-antibody titers measured by this assay. The significance of low-titer anti-AAV8 NAbs is shown, along with the relevance of the in vitro assay cutoff (1:5) compared with other assays. Importantly, internally standardized reagents and purified AAV8 constructs containing 90% full capsids were used to reduce the effect of empty capsids. It was found that even very low anti-AAV8-NAb titers (<1:5) could efficiently hinder transduction in vivo, demonstrating the importance of sensitive NAb assays for clinical applications. The in vitro NAb assay was found to be more sensitive than an in vivo NAb assay and thus more suitable for patient screening. Additionally, the study showed that anti-AAV8-NAb titers <1:5 were very rare, further supporting the in vitro assay. However, assays using a lower cutoff may still be useful to explain potential variances in transgene expression. These findings support the relevance of the higher than expected prevalence of anti-AAV8 NAbs, highlighting the need for strategies to circumvent preexisting anti-AAV8 NAbs."

Suitability of In vitro Neutralizing Antibody Assay to Detect low antibody titers against AAV Suitability of In vitro Neutralizing Antibody Assay to Detect low antibody titers against AAV Reviewed by Biotechnology on September 17, 2019 Rating: 5

Preexisting antibody and T cell response against AAVs

September 17, 2019
Kruzik et al. recently published a paper (Molecular Therapy, 2019) reporting the prevalence of the preexisting immune response against adeno-associated virus (AAV) among 200 international cohorts from the US and EU region. The following are the excerpts from the study. 



Journal Molecular Therapy: Methods & Clinical Development
Abstract"Preexisting immunity against adeno-associated virus (AAV) is a major challenge facing AAV gene therapy, resulting in the exclusion of patients from clinical trials. Accordingly, proper assessment of anti-AAV immunity is necessary for understanding clinical data and for product development. Previous studies on anti-AAV prevalence lack method standardization, rendering the assessment of prevalence difficult. Addressing this need, we used clinical assays that were validated according to guidelines for a comprehensive characterization of anti-AAV1, -AAV2, -AAV5, and -AAV8 immunity in large international cohorts of healthy donors and patients with hemophilia B. Here, we report a higher than expected average prevalence for anti-AAV8 (∼40%) and anti-AAV5 (∼30%) neutralizing antibodies (NAbs), which is supported by strongly correlating anti-AAV IgG antibody titers. A similar anti-AAV8 NAb prevalence was observed in hemophilia B patients. In addition, a high co-prevalence of NAbs against other serotypes makes switching to gene therapy using another serotype difficult. As anti-AAV T cell responses are believed to influence transduction, we characterized anti-AAV T cell responses using interleukin-2 (IL-2) and interferon-γ (IFN-γ) ELISpot assays, revealing a similar prevalence of IFN-γ responses (∼20%) against different serotypes that did not correlate with NAbs. These data, along with the long-term stability of NAbs, emphasize the need to develop strategies to circumvent anti-AAV immunity."

Preexisting antibody and T cell response against AAVs Preexisting antibody and T cell response against AAVs Reviewed by Biotechnology on September 17, 2019 Rating: 5

Medical Microbiology: MCQ on Hepatitis viruses, infection and transmission

September 12, 2019

Multiple Choice Question of Hepatitis viruses, types, infection and transmission

1) Which of the following organ is primarily infected by Hepatitis viruses?
a) Intestines
b) Gall bladder
c) Stomach
d) Liver

2) All of the following are the type RNA virus, EXCEPT?
a) Hepatitis A
b) Hepatitis B
c) Hepatitis C
d) Hepatitis D

3) Which of the following virus is NOT transmitted through the parenteral route?
a) Hepatitis A
b) Hepatitis B
c) Hepatitis C
d) Hepatitis D

4) Hepatitis A virus (HAV) belongs to which of the following family of viruses?
a) Hepadnaviridae
b) Hepeviridae
c) Picornaviridae
d) Flaviviridae

5) All of the following are the important structural characteristics of the Hepatitis B virus (HBV) EXCEPT?
a) The size of the virus is 42 nm in diameter
b) The envelope consists of surface antigen (HBsAg) and lipid
c) Consists of the single-stranded RNA genome
d) The mode of transmission is parenteral

6) All of the following statements regarding HBV infection is true, EXCEPT?
a) Acute liver infection is subclinical in about 70 percent
b) Chronic hepatitis B can lead to cirrhosis and liver cancer
c) Infants born to infected mothers can have this virus
d) Medications are not available for the treatment of the chronic hepatitis B infection

7) Which of the following is the major risk factor for the Hepatitis C virus (HCV)infection in the United States of America?
a) Sexual activity
b) Use of drugs
c) Blood transfusion
d) Tattoos

8) Hepatitis D virus is also known as the delta virus requires HBV to cause infection in people
a) TRUE
b) FALSE

9) Hepatitis E virus (HEV) infection is more commonly found in developing countries which is transmitted mostly through contaminated water, all of the following are the signs and symptoms of HEV, EXCEPT?
a) Blood in the stool
b) Nausea and vomiting
c) Yellowing of the skin
d) Low-grade fever

10) Which of the following statement is true for hepatitis causing viruses HAV, HCV, HDV, and HEV?
a) Transmitted via the fecal-oral route
b) Transmitted via the parenteral route
c) Contain a single-stranded RNA genome
d) Can lead to liver cancer

11) Which of the following group of people are NOT considered in the increased risk of acquiring HAV infections?
a) People traveling to developed countries to developing countries
b) Men having a sexual relationship with other men
c) People working with primates
d) From infectious pregnant women to their babies >

12) A 32-year-old man comes to the clinic with abdominal discomfort and vomiting, low grade and fever, the diagnosis was done and is found to be infected with HAV. In a blood sample, IgM antibodies detection confirms the HAV infection, how long after the initial infection these antibodies are found in the blood?
a) 24 hours
b) 3 to 4 days
c) 1 to 2 weeks
d) 12 hours

13) All of the following statements are true for the diagnosis of HBV infection, EXCEPT?
a) Tests for the detection of elevated liver enzymes should be done
b) Serological tests to detect
c) Liver function test- bilirubin
d) Glucose challenge test       

14) Which of the following statements about HDV is NOT correct?
a) RNA virus
b) Transmitted by parenteral route
c) Can replicate only when in a cell that is also infected by HBV
d) None of the above

15) According to the World Health Organization's recent survey, about what percentage of people know they are living with Hepatitis infection?
a) 75 %
b) >5 %
c) 25 %
d) 50 %

16) What are the other risk factors that can cause hepatitis infection apart from virus, Select all the correct answers?
a) Abuse of drugs
b) High alcohol consumption
c) Fatty liver
d) Autoimmune infection

17) Which of the following statements is NOT correct about the vaccination of HAV, HBV, and HCV?
a) Hepatitis A vaccination should be started when kids are 1 year old
b) Newborns from infected mothers are only required to get the HBV vaccine
c) There is no vaccine available for HCV
d) All of the above

18) HEV can cause epidemics of jaundice, more commonly seen in developing countries. All of the following are the most common sources of HEV, EXCEPT?
a) Contaminated water
b) Raw or undercooked pork
c) Contaminated blood products
d) A sexual relationship with an infected individual

19) All of the following statements about the HEV is true, EXCEPT?
a) Transmitted by the fecal-oral route
b) It is a non-enveloped virus
c) The major cause of hepatitis liver cancer
d) Found in rodents and pigs

20) Hepatitis C infection in the USA is increasing among young adults in the USA, there is more than 100 % increase since 2005 particularly seen among young adults. Which of the following is the most common cause of this infection?
a) Injecting drug use
b) Sexual relation
c) Baby born to an infectious mother
d) Sharing razors and toothbrushes


Answers
1) d) Liver
2) b) Hepatitis B
3) a) Hepatitis A
4) c) Picornaviridae
5) c) Consists of the single-stranded RNA genome
6) d) Medications are not available for the treatment of the chronic hepatitis B infection
7) c) Blood transfusion
8) a) TRUE
9) a) Blood in the stool
10) c) Contain a single-stranded RNA genome
11) d) From infectious pregnant women to their babies
12) c)1 to 2 weeks
13) d) Glucose challenge test           
14) d) None of the above
15) b) >5 %
16) All options above
17) b) Newborns from infected mothers are only required to get the HBV vaccine
18) d) A sexual relationship with the infected individual
19) c) The major cause of hepatitis liver cancer
20) a) Injecting drug use


Medical Microbiology: MCQ on Hepatitis viruses, infection and transmission Medical Microbiology: MCQ on Hepatitis viruses, infection and transmission Reviewed by Biotechnology on September 12, 2019 Rating: 5

MCQ on Heme synthesis & Related Inherited Disease (Porphyria)

August 27, 2019

Multiple Choice Question on Heme synthesis & Related Inherited Disease (Porphyria)

1) Heme is a tetrapyrrole structure consisting of Fe+2 ions in the center of the porphyrin ring. Which of the following proteins consist of heme?
a) Myoglobin
b) Hemoglobin 
c) Cytochrome
d) All of the above



2) Besides erythroid precursor cells, which of the following is the site for the synthesis of heme?
a) Kidney
b) Spleen
c) Liver
d) Heart

3) Which of the following is not the precursor for the synthesis of Heme?
a) Glycine
b) Succinyl CoA
c) Both of the above
d) None of the above

4) Which of the following is the rate-limiting enzyme for the synthesis of heme?
a) delta-aminolevulinic acid synthase 1
b) Uroporphyrinogen synthase III
c) Protoporphyrinogen oxidase
d) Ferrochelatase


5) The synthesis of heme involves both cytosolic and mitochondrial cellular compartment. Which of the following enzyme-catalyzed reaction does not occur in the cytosol?
a) delta-aminolevulinic acid synthase 1
b) Uroporphyrinogen synthase III
c) Protoporphyrinogen oxidase
d) Ferrochelatase

6) Lead positioning causes the increases the accumulation and urinary excretion of coproporphyrin III and ALA in the urine. Which of the following enzyme is inhibited by lead metal?
a) ALA synthase and Protoporphyrin oxidase
b) ALA synthase and Ferrochelatase
c) ALA dehydratase and Protoporphyrin oxidase
d) ALA dehydratase and Ferrochelatase

7) The heme, hematin and Cytochrome P450 represses the synthesis of the following enzyme thereby reducing heme synthesis.
a) delta-aminolevulinic acid synthase 1
b) Uroporphyrinogen synthase III
c) Protoporphyrinogen oxidase
d) Ferrochelatase

8) Which of the following intermediate of the heme synthetic pathway is water-insoluble and excreted via feces via biliary tract?
a) delta-aminolevulinic acid
b) Porphobilinogen
c) Uroporphyrinogen
d) Protoporphyrin


9) The porphyrias are a group of metabolic disorders that result from partial deficiencies of the enzyme of the heme biosynthetic pathway. The porphyria may be classified as acute and nonacute. Which of the following porphyria is not acute type?
a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Variegate porphyria
d) Porphyria cutanea tarda

10) Identify porphyria that does not have accumulation and increased excretion of delta-aminolevulinic acid and porphobilinogen among the following:
a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Congenital erythropoietic porphyria
d) Variegate porphyria

11) Porphyria Cutanea Tarda (PCT) is the most common porphyria characterized by photosensitivity, skin lesions. Which of the following statement is false regarding PCT
a) PCT is caused by the deficiency of uroporphyrinogen decarboxylase enzyme
b) Accumulation of photo-sensitizers such as uroporphyrinogen and carboxyl-substituted porphyrinogen
c) Accumulation of ALA (delta-aminolevulinic acid) and PBG (porphobilinogen)
d) None of the above

12) Which of the following is the most sensitive method for the measurement of porphobilinogen?
a) Colorimetric Ehrlich's reaction method
d) Ion exchange chromatography based method
c) HPLC coupled MS
d) Spectral analysis of porphobilinogen

13) All of the porphyrias are inherited in autosomal dominant fashion except the following two autosomal recessive conditions
a) ALA synthase deficiency
b) ALA dehydratase deficiency
c) Congenital erythropoietic porphyria
d) Hereditary coproporphyria

14) The enzyme deficient in erythropoietic protoporphyria is
a) delta-aminolevulinic acid synthase 1
b) Uroporphyrinogen synthase III
c) Protoporphyrinogen oxidase
d) Ferrochelatase

15) The intravenous administration of hemin is required for reducing symptoms during acute porphyria attacks. The hemin decreased the  gene synthesis of the following enzyme
a) delta-aminolevulinic acid synthase 1
b) Uroporphyrinogen synthase III
c) Protoporphyrinogen oxidase
d) Ferrochelatase

Answers
1-d) All of the above
2-c) Liver
3-d) None of the above
4-a) delta-aminolevulinic acid synthase
5- b) Uroporphyrinogen synthase III
6-d) ALA dehydratase and Ferrochelatase
7)- a) delta-aminolevulinic acid synthase 1
8)-d) Protoporphyrin
9)-d) Porphyria cutanea tarda
10)- c) Congenital Erythropoietic porphyria
11)-c) Accumulation of ALA (delta-aminolevulinic acid) and PBG (porphobilinogen)
12) -c) HPLC coupled MS
13)- b) ALA dehydratase deficiency & c) Congenital erythropoietic porphyria
14)-d) Ferrochelatase
15-a) delta-aminolevulinic acid synthase 1


Heme Synthesis & Porphyria (Diagram NEMJ)

MCQ on Heme synthesis & Related Inherited Disease (Porphyria) MCQ on Heme synthesis & Related Inherited Disease (Porphyria) Reviewed by Biotechnology on August 27, 2019 Rating: 5

Medical Microbiology: MCQ on Human Immunodeficiency Virus (HIV/ AIDS)

August 27, 2019

Multiple Choice Question on Human Immunodeficiency Virus (HIV/AIDS)


1) There are two types of HIV (Human immunodeficiency virus) viruses- HIV 1 & HIV 2. HIV 1 virus is found worldwide.  HIV 2 (a less pathogenic than HIV 1) is mainly found in which part of the world?
a) Asia
b) West Africa
c) Northern Europe
b) North America

2) Which of the following is an important molecule present in the outer membrane of the HIV that helps to enter the host cell?
a) Polysaccharides
b) Glycoproteins
c) Proteins
d) Lipopoysaccharides

3) All of the following are the examples of the route through which HIV can be transmitted from one person to another, EXCEPT?
a) Unprotected sexual contact with an infected person
b) From infected mother to the fetus
c) From the mosquito bite carrying the virus
d) Exposure to contaminated blood and blood products

4) HIV belongs to which of the following genus member of the virus?
a) Orthomyxovirus
b) Lentivirus
c) Parvovirus
d) Reovirus

5) All of the following statements regarding HIV infection in human is true, EXCEPT?
a) Person once infected will remain infected for life if untreated
b) Monocytes and macrophages are the major reservoirs of the virus
c) The opportunistic infections in AIDS are mainly due to the loss of cell-mediated immunity
d) The center of the virus has the main antigenic properties

6) Which of the following enzyme is required for viral replication and plays a critical role in the pathogenesis of HIV infection?
a) RNA polymerase
b) DNA polymerase
c) RNA polymerase II
d) Reverse transcriptase

7) The envelope protein gp120 (Glycoprotein 120) is required for the attachment of the HIV virus to CD 4 receptors of target host cells. Identify the immune cells that consist of CD 4 receptors?
a) T helper cells
b) Monocytes
c) Macrophages
d) Dendritic cells

8) Identify the chemokine receptor cell present in the host macrophages that helps in the primary attachment of HIV?
a) CxCR 4
b) CCR5
c) Both of the above
d) None of the above

9) Which of the following is an important HIV antigen in determining the early detection of HIV infection?
a) p24
b) gp120
c) Pol gene
d) Gp120

10) In many patients, the chronic HIV infection progresses to AIDS (Acquired Immunodeficiency Syndrome) which is characterized by multiple opportunistic infections. Which of the following common bacterial infections is seen globally in HIV infected patients?
a) Pneumocystis carinii pneumonia
b) Tuberculosis
c) Candidiasis
d) Toxoplasmosis

11) When was the first human AIDS case reported in the USA?
a) 1990
b) 1982
c) 1981
d) 1991

12) Highly active antiretroviral therapy (HAART) is a combination therapy that includes protease inhibitor class drugs like indinavir and saquinavir and other drugs prescribed for HIV infection. What is the main goal of these drugs?
a) Inhibitors of the enzyme protease
b) Inhibits viral replication and viral load
c) Prevents the interaction between the virus and the coreceptor
d) All of the above

13) All of the following are the examples of a biological specimen that can be taken for the laboratory diagnosis of HIV infection, EXCEPT?
a) Blood
b) Saliva with the presence of blood
c) Genital secretions
d) Urine with no presence of blood

14) Which of the following drug can significantly reduce the transmission of HIV infection from mother to baby?
a) Acyclovir
b) Zidovudine
c) Ceftriaxone
d) None of the above

15) All of the following are the current preventive methods of HIV infection, EXCEPT?
a) Safe and protected sex
b) Use of available vaccines
c) Use of sterile injection needles
d) All of the above


Multiple Choice Answers
1)- b) West Africa
2)- b) Glycoprotein
3)- c) From the mosquito bite carrying the virus
4)- b) Lentivirus
5)- d) The center of the virus has the main antigenic properties
6)- d) Reverse transcriptase
7)- a) T helper cells
8)- b) CCR5
9)- a) p24
10)- b) Tuberculosis
11)- c) 1981
12)- b) Inhibits viral replication and viral load
13)- d) Urine with no presence of blood
14)- b) Zidovudine
15)- b) Use of available vaccines 
Medical Microbiology: MCQ on Human Immunodeficiency Virus (HIV/ AIDS) Medical Microbiology: MCQ on Human Immunodeficiency Virus (HIV/ AIDS) Reviewed by Biotechnology on August 27, 2019 Rating: 5
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