This document discusses pre-clinical screening methods for immunomodulatory drugs. It begins with an introduction to immunomodulators and how they can suppress or stimulate the immune system. It then describes various in vitro and in vivo methods used to test immunosuppressant drugs, including inhibition of histamine release from mast cells, mitogen-induced lymphocyte proliferation assays, and animal models like acute systemic anaphylaxis in rats. The document provides details on the procedures and evaluations of several common pre-clinical screening techniques.
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Assignment on Preclinical screening of new substances for the pharmacological activity using in vivo, in vitro, and other possible animal alternative models
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Assignment on Preclinical screening of new substances for the pharmacological activity using in vivo, in vitro, and other possible animal alternative models
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Introduction to Screening Models Of Anti Cancer Drugs
Need for novel anti cancer drugs, In - vitro methods, In - vivo methods, Advantages and disadvantages
Presented by
T. Niranjan Reddy
Department of Pharmacology
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
Screening methods of immunomodulators by shivam diwakerShivam Diwaker
Immune Modulators are the substances or drugs or chemical compounds that are used for the modification in the Immune system such as stimulate and suppress.
Screening models for immunomodulatory agents:- Introduction for immunostimulants and immunosuppressant, Models for immunomodulatory agents, Screening for immunostimulants, screening for immunosuppressant
Introduction to Screening Models Of Anti Cancer Drugs
Need for novel anti cancer drugs, In - vitro methods, In - vivo methods, Advantages and disadvantages
Presented by
T. Niranjan Reddy
Department of Pharmacology
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
Screening methods of immunomodulators by shivam diwakerShivam Diwaker
Immune Modulators are the substances or drugs or chemical compounds that are used for the modification in the Immune system such as stimulate and suppress.
Screening models for immunomodulatory agents:- Introduction for immunostimulants and immunosuppressant, Models for immunomodulatory agents, Screening for immunostimulants, screening for immunosuppressant
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Contents :-
• Introduction
• Mechanism of action of immunosuppressant drug
• In-vitro methods
• In-vivo methods
• References
3. • IMMUNITY
The ability of an organism to resist
a particular infection or toxin.
WHAT IS ANTIGEN AND ANTIBODY ?
• ANTIGEN
An antigen is any foreign substance.
• ANTIBODY
It is an immunoglobulin produced by B-cells.
4. Introduction:-
• Immunomodulators are the agents that modulate immune system by suppressing
or by stimulating immune response
• Immunomodulation as part of immunotherapy, in which immune responses are
induced, amplified, attenuated, or prevented according to therapeutic goals
• Immunomodulators divided into two parts :-
- Immunosuppressant
- Immunostimulant
5. Immunostimulant drugs Immunosuppressant drugs
Stimulate response in case of
immunodeficiency
Inhibitory response in case of organ
transplantation
Levamisole Specific T-cell inhibitors- cyclosporin,
tacrolimus
Thalidomide Cytotoxic drugs- Azathiopurines
methotrexate,
Bacillus Calmette Guerin Glucocorticoids –Prednisolone
Interferons Antibodies –Muromonab CD3,
antithymocyte globulin
Interleukin-2
6. Mechanism of action of immunosuppressant drugs:-
1.Glucocorticoides
2.Cytotoxic drugs
3.T-cell inhibitor
4.Antibodies
7. • 1. Glucocorticoids inhibit MHC expression and IL-1, IL-2, IL-
6 production so that helper T-cells are not activated.
• 2. Cytotoxic drugs block proliferation and differentiation of
T and B cells.
• 3. Cyclosporine, tacrolimus and sirolimus inhibit antigen
stimulated activation and proliferation of helper T cells as
well as expression of IL-2 and other cytokines by them.
• 4. Antibodies like muromonab CD3, antithymocyte globulin
specifically bind to helper T cells, prevent their response
and deplete them.
9. IN-VITRO METHODS
• Inhibition of histamine from mast cells
• Mitogen induced lymphocyte proliferation
• Inhibition of T cell proliferation
• Chemiluminescence in macrophages
• PFC (plaque forming colony) test in vitro
• Inhibition of dihydro-orotate dehydrogenase
10. IN-VIVO METHODS :-
• Acute systemic anaphylaxis in rats
• Antianaphylactic activity (Schultz-Dale reaction)
• Passive cutaneous anaphylaxis
• Arthus type immediate hypersensitivity
• Delayed type hypersensitivity
• Reversed passive arthus reaction
• Acute graft versus host disease in rats
• Collagen type-Ⅱ induced arthritis in rats
• Adjuvant arthritis in rats
• Porcine cardiac myosin-induced autoimmune myocarditis
in rats
11. Inhibition of histamine release from mast cells :-
• Purpose and rationale :-
Histamine release induce from mast cell by calcium ionophore 48/80.
Histamine concentration can be determined with o-phthalaldehyde reaction
• Procedure :-
1. Preparation Of mast cell suspension :-
Wistar rat decapitated and exsanguinated
50ml HBSS inj. Into peritoneal cavity
Massage body abdominal wall is open
Fluid containing peritoneal cell is collected
Centrifuge at 2000 rpm
Cells resuspended in HBSS
brought final concentration of 105 mast cells/100𝜇l
12. • Test compound administration and induction of histamine
release :-
1ml test drug + mast cell suspension
Incubate 37°c for 15 min
Make 3ml vol with HBSS
Equal vol of calcium ionophore with allergen
Suspension incubate 37°c 30min
Centrifuge at 2500 Rpm
Control solutions :-
• Spontaneous histamine release – only mast cells and solution
determine baseline
• Histamine release – mast cell + solution +calcium ionophore 10-6g/ml
• Test compound control – solutions +test compound
13. 1ml top layer transfer to
Tube contain 300mg Nacl+1.25 butanol
Sample alkalized by adding 1ml 3N NaoH
Centrifuge for 5min
1ml top layer (butanol) is pipetted out
In 5ml tube containing 2ml n-heptane+0.4ml of 0.12N HCl
Mixing by inverting tube
Separation of aq. and org. phase
0.5ml aqueous phase transfer to tube
Extraction of Histamine
15. • Critical assessment of the method :-
Disodium cromoglycate reported to inhibit release of histamine and
degranulation of rat mast cells
• Modification of method :- sensitive colorimetric assay for release of
tryptase from human lung mast cells in vitro has been described by
Lavens et al. (1993)
16. Mitogen Induced Lymphocyte Proliferation :-
• Purpose and rationale :-
Immunomodulatory properties can detected either by pretreatment of
animal in vivo or by adding test drug to cultured lymphocyte
• Procedure :-
Mice of weight 18-20g or Rat 180-200g are used
Materials :-
Antigen and or following mitogens :
Lipopolysaccharide 10-0.1 micro/ml
Dextran sulfate 30-7.5 micro/ml
Phytohaemaglutinin 0.5-0.12 %stock solution
Concanavallin A 0.5-0.12 micro/ml
Standards – levamisole, cyclosporine A, prednisolone
17. After drying degree of radioactivity is determined
Cells are harvested on glass fibre filter
Another 8h after addition of 0.25𝜇𝐶 H-thymidine per well
Plates incubated at 37℃ in 5% CO2 in air for 48-60 h
Mitogens are titrated in 0.1ml/well and add 0.1ml suspension
Single cell suspension of 5× 106 cells /ml
Sacrifice and spleen is removed
Animal treated with test compound once a day for 5days
Ex-Vivo:-
18. • In-vitro :-
Animals sacrifice spleen removed
Single cell suspension of 107 cells /ml prepared
0.05ml place in each microtiter well
Test compound is added in 0.05ml
At last 0.1ml mitogen added
Plates incubated and processed as above
Evaluation:- stimulation index=proliferation ratio with or without spleen mean weight
19. IN-VIVO:- 1. Acute Systemic Anaphylaxis in rats :-
• Purpose and rationale :-
Detection of shock symptoms and it can be inhibited by corticosteroid and i.v
disodium cromoglycates
• Procedure :-
Female Sprague dawley rat 120g
Immunized by i.m inj. 10mg/kg high purified ovalbumin with 1ml Bordetella
pertussis suspension
IgE Ab are induce and attach to surface of mast cells, After 11 days
Animals challenged by i.v. inj. Of 25mg/kg ovalbumin
20. Formation of Ag-Ab complex in blood/organs
Then immediate anaphylaxis mediators release
Corticosteroid e.g. dexamethasone 1-10mg/kg s.c. Or 30mg/kg disodium cromoglycate
(before 18h challenged )
21. • Evaluation :- Shock symptoms are scored and mortality counted
• Modification of the method :-
elwood et al. (1992) studied the effect of dexamethasone and
cyclosporin A on allergen-induced airway hyperresponsiveness and
inflammatory cell responses in sensitizes brown –Norway rats.
22. Anti-anaphylactic activity (Schultz-dale reaction)
• Purpose and rationale :- guinea pig are sensitized against egg albumin.
Challenge after 3weeks cause isolated organs release mediators e.g. histamine
• Procedure :-
Guinea pig of either sex sensitized with alum precipitated egg albumin.
Alum egg albumin is prepared by dissolving egg albumin (1mg/ml)in 6% aluminum
hydroxide gel, suspended in saline.
Mixture is stirred and kept at room temperature.
Each animals receives at same time injection of 0.125ml of this mixture in each foot pad
and 0.5ml s.c
After 4weeks animals are killed and ileum is dissected out.
23. Cleaned pieces, about 2-3cm long, are mounted in organ bath containing Tyrode solution at
37℃.
Strips allowed to equilibrate for 15min.
Contractility of ileum strip is tested by adding 10-4 g/ml BaCl2 solution.
To one organ bath standard and to other test compound added.
After 3min ovalbumin in final concentration of 2× 10 -6g/ml is added
Contraction recorded with strain gauges by polygraph.
24. • Evaluation :-
If anti-anaphylactic activity is observed, ED50 value using different doses
are calculated.
• Modification of method :-
Trachea of sensitized guinea pigs was used by omote et al.
(1994)
25. References :-
• Hans Gerhard Vogel. Drug discovery and evaluation: Pharmacological assays, vol 2, 3rd edition. Pg
no.792-799
• KD Tripathi, Essentials of Medical Pharmacology, Jaypee publications, Seventh edition, Pg no.778-
788