Cohn's fractionation method from the 1940s remains pivotal for plasma fractionation. It allows industrial-scale albumin production and generates fractions with therapeutic interest. The process uses ethanol precipitation under varying conditions to enrich plasma proteins. Additional purification steps like chromatography are needed to produce final therapeutic products. Safety improvements like viral removal filters and solvent-detergent treatment were later incorporated. Plasma fractionation now recovers over 30 million liters annually worldwide. India could better utilize recovered plasma through local or contracted fractionation to produce important proteins like albumin, immunoglobulins and clotting factors.
The present document provide the information about Methods of extraction of drugs from the biological matrix (protein precipitation method, liquid extraction)
Hemostasis is the arrest of bleeding, whether it be by normal vasoconstriction (the vessel walls closing temporarily), by an abnormal obstruction (such as a plaque) or by coagulation or surgical means (such as ligation)
A blood clot (thrombus) developed in the circulatory system can cause vascular
blockage leading to serious consequences including death. A healthy hemostatic system
suppresses the development of blood clots in normal circulation, but reacts extensively in
the event of vascular injury to prevent blood loss. Outcomes of a failed hemostasis include
stroke, pulmonary embolism, deep vain thrombosis and acute myocardial infraction
pathogen inactivation of cellular components.pptxDrShinyKajal
Chemical inactivation
Photo-inactivation
Solvent-detergent Plasma
Photosensitizers
Methylene Blue light treatment
Psoralen Ultraviolet Light Treatment
Riboflavin Light Treatment
INTERCEPT System
Mirasol system
Platelet and plasma Pathogen Inactivation
FRALE and azridine compounds
The present document provide the information about Methods of extraction of drugs from the biological matrix (protein precipitation method, liquid extraction)
Hemostasis is the arrest of bleeding, whether it be by normal vasoconstriction (the vessel walls closing temporarily), by an abnormal obstruction (such as a plaque) or by coagulation or surgical means (such as ligation)
A blood clot (thrombus) developed in the circulatory system can cause vascular
blockage leading to serious consequences including death. A healthy hemostatic system
suppresses the development of blood clots in normal circulation, but reacts extensively in
the event of vascular injury to prevent blood loss. Outcomes of a failed hemostasis include
stroke, pulmonary embolism, deep vain thrombosis and acute myocardial infraction
pathogen inactivation of cellular components.pptxDrShinyKajal
Chemical inactivation
Photo-inactivation
Solvent-detergent Plasma
Photosensitizers
Methylene Blue light treatment
Psoralen Ultraviolet Light Treatment
Riboflavin Light Treatment
INTERCEPT System
Mirasol system
Platelet and plasma Pathogen Inactivation
FRALE and azridine compounds
Large quantities of donated blood are discarded due to stability issues. Stocks of rare blood types rarely last more than a week. Therefore there is considerable value in achieving more stable material.
This study was carried out in conjunction with the University of Cambridge and sponsored by the UK TSB.
Jehowah's witnesses and blood conservation strategies by Dr.Minnu M. PanditraoMinnu Panditrao
dr. Mrs. Minnu M. Panditrao explains the problems faced by anesthesiologists in anesthetising the Jehowah's Witness patients because of their beliefs. Ina ddition she also discribes various strategies of Blood conservation.
An artificial blood or recombinant Hemoglobin is very beneficial as it can be produced homogeneously and inexhaustibly in factories. It is genetically altered hemoglobin from E-coli result in functional hemoglobin which avoids infectious risk.
Understanding of hemophilia increased over years, better understanding now lead us to better comprehensive care for such unfortunate patients. this presentation is derived from the text of world federation of hemophilia and indian academy of pediatrics.
DIC is one condition that always trouble patients and doctor, though its a nightmare for any clinician , its also a potent question in both UG and PG exams. I hope this will help you in answering those questions well.
Selection of blood donor is the foremost and most important part in ensuring safe blood supply, donor selection guidelines has been revised by NBTC from time to time, this upload is of 2017
its sometime difficult to decide in urgent clinical scenarios - Trauma,active bleeding, surgery: What ; when ; how and why to transfuse? answering some of these queries here is my presentation especially made for PG students (will help in answer writing)
The collection and processing of hematopoieticakshaya tomar
BASICS OF HSC COLLECTION AND PROCESSING INCLUDING ALL THE THREE SOURCES, A BRIEF ABOUT STEM CELL MOBILIZATION, STEM CELL SELECTION CRYOPRESERVATION AND DMSO
ITS ALL ABOUT UMBLICAL CORD CELLS, ITS PRESENT USE, TECHNIQUES OF COLLECTION AND PROCESSING ALONG WITH EX VIVO EXPANSION
FEW VIDEOS ARE ALSO THERE BUT YOU CANNOT ACCESS IT
most controversial topic in the field of transfusion medicine, most of the transfusions worldwide are associated with the deleterious effects of immunomodulation, simplified for PG students with latest article support
description about RBC membrane and its structural peculiarities,how it differs from other cells of our body. How this specialized cell manage homeostasis and function in a well defined manner. This presentation will also help in understanding various RBC storage lesions ,an important aspect of blood banking.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. INTRODUCTION
• The procedure that continues to have a pivotal role in
plasma fractionation was developed by Cohn in 1940s.
• In terms of global demands , the volume of plasma
fractionated has been steadily increasing in the last few
years.
• The developing world uses a small portion of the
fractionated plasma products as a result of product
shortages and lack of purchasing power for these
sophisticated medicinal products
3. INTRODUCTION
• In India number of units of whole blood collected is
approx 5-10units/1000 people
• WHO estimated that about 9.3 million liters of recovered
plasma is wasted or discarded yearly worldwide.
• Currently therapeutically important proteins are:
- Human serum albumin
- Igs
- Coagulation factor VIII
- Protease inhibitors
4. INTRODUCTION
• Human serum albumin is one of the most abundant
proteins in plasma and together with Igs constitutes 80%
of all plasma proteins
• The average HSA consumption in the developed world is
200-400 kg per million population and IVIG use was at
20-40 kg IgG per million
• The volume of plasma fractionated has been steadily
increasing in the last few years, and has now reached
close to 35 million liters worldwide, compared to
approximately 25 million liters some 10 years ago
5. INTRODUCTION
• Cohn’s method for producing albumin achieved 2
outcomes:-
- It allowed the industrial scale manufacture of albumin
- It generated a series of fractions that immediately aroused
therapeutic interest
6. INTRODUCTION
• Plasma fractionation is unique in a way that it requires
integrated downstream purification and viral reduction
processes.
• Extraction processes should be mild to avoid the risks of
alterations that could lead to protein antigenicity or
activation that results in
- Hypotension
- Fever
- Thromboembolic events
7. Emerging Viral Threats
• West nile virus
• Dengue virus
• Chikungunya virus
• SARS virus
• Hepatitis E virus
It seems scientifically reasonable to conclude that potential
residual infectious risks for most plasma products would
be restricted to emerging resistant small (<15-20 nm)
non-enveloped viruses
10. History
• Cohn’s developed stable plasma protein solution for the
treatment of battlefield injuries in the 2nd World War.
• Resulting albumin product remained the mainstay of the
plasma fractionation
13. Safety issues
• Until the late 1970s safety was not a major concern for
plasma protein therapies
• Albumin and Ig were associated with hepatitis but it was
obviated by heating the product at 60°C for 10 hrs
• But hemophiliacs who are on continuous replacement
therapy receiving less purified fractions were carrying
major risk of transmission
• This leads to introduction of NAT for Plasma fractions
14. The Cohn Process
• It is based on the differential precipitation of plasma
proteins by manipulation of
- ethanol concentration
- pH of a Low ionic strength concentration
- maintained at subzero temperature
• Each Cohn fraction is an enriched , albeit crude , source
of various plasma protein need further purification to
generate a therapeutic product.
15.
16. Variation to Cohn’s Process
• Kistler and Nitschmann in 1962
• To maximize Albumin yield and decrease ethanol use
• This method is adopted by CSL Behring
18. Viral removal procedures
• It is achieved by precipitation of fractions
• Regulatory requirements however require inclusion of at
least 2 dedicated orthogonal viral removal procedure
• Viral Filters: -15-20nm pore size , thereby ensuring the
removal of small non-enveloped viruses such as
Parvovirus B19
- 35nm pore size, removing large enveloped viruses
such as hepatitis B and C and HIV
19. Viral removal procedures(Other)
• Solvent Detergent Method – For enveloped viruses
• Nanofilteration – for Non enveloped viruses as well as
Prions
• Pasteurization – Heating at 60°C for 10 hours
• Caprylic acid treatment – Incubation at low pH at 30°C
for 10 hours
20. Chromatographic Procedures
• Cohn fractionation generate highly purified albumin and
immunoglobulin products
• Chromatographic techniques allow purification of
proteins because of their differences in molecular weight
, charge , hydrophobicity and specific affinity for ligands
(eg: diethylaminoethyl, quarternary amino ethyl)
• This involves the use of size exclusion, ion exchange,
hydrophobic interaction and affinity chromatography
respectively
21. Chromatographic Procedures
• Ion exchange chromatographic resins exist in either the
anion or cation forms
• Net charge of a protein depends on pH and this
determines the degree of interaction with an ion
exchange resin
• Chromatographically purified Albumin is of green color
22. Chromatographic Procedures
• Interaction can be further modulated by changes in ionic
strength
• Thus by utilizing conditions that promote differential
binding to ion exchange resins , coupled with defined
elution conditions fractionation of a mixture of proteins
can be achieved
23. Chromatographic Procedures
• Proteins exhibit differences in their hydrophobic profile
• This difference is exploited in hydrophobic interaction
chromatography (HIC)
• Solution conditions can be manipulated such that more
hydrophobic proteins are retained on a column while less
hydrophobic proteins flow through
24. Advantages of Cohn’s Fractionation
• Ethanol is cheap and easily available
• Accepted, processes and products are registered
• Process under bacteriostatic conditions
• Products may be regarded as safe in therapeutic use
• Suited to large-scale production
25. Disadvantages of Cohn’s Fractionation
• Cold areas or refrigerated tanks required
• Protein losses occur in occluded liquor
• Not suited to small scale production
• Requires high quality starting material
26. PRODUCTS WITH ESTABLISHED
CLINICAL USE
• Albumin
• Immunoglobulins
• vWF
• Factor IX , X , XIII
• Prothrombin complex concentrates(PCC)
• Fibrinogen
• α1 Proteinase inhibitor
• C1 esterase inhibitor
29. CONCLUSION
• In medium income countries like ours, RBCs need will
surpass that of FFP and Cryoprecipitate by 2025
• This will generate lot of recovered plasma but due to
underutilization it will get wasted
• One major issue is that currently collected plasma in low-
and medium-income countries typically does not meet
specifications for fractionation and is therefore discarded
30. CONCLUSION
• Contract Fractionation : A pragmatic way to go
it can overcome
- Technological challenges
- Economic considerations
• It can be utilized for interim period of 5 years by
domestic fractionation facility
• Minimum Plasma required is 10,000L / annum but most
fractionators prefers at least 30,000 to 50,000L/year (due
to logistics and licensing issues)
31. CONCLUSION
• It is important that both plasma collection and
fractionation are performed following standards
established at a global level
• It is likely that the future will be as eventful as the period
from Cohn to the present day