This document discusses a potential solution to problems with blood transfusions called "immunocamouflaged red blood cells" or "stealth RBCs". The stealth RBCs are created by covalently grafting polymers like methoxypoly(ethylene glycol) to the surface of donor red blood cells. This process masks the blood group antigens and prevents the recipient's immune system from recognizing the cells as foreign. The stealth RBCs could help prevent alloimmunization from mismatched blood and allow for transfusions in patients with rare blood types or multiple alloantibodies. Large-scale production of stealth RBCs is possible using existing blood bag equipment and technologies. Further testing is still needed but stealth R
leucodepletion is the removal of 99% leucocytes from the whole blood, pcv or platelets before transfusing into the donor.
this process many infections, transfusion reactions..
Red cell and platelet storage lesions and their effect in transfusion practiseArjuna Samaranayaka
Bio mechanical and metabolic changes that occur in red cell concentrates and platelets during ex-vivo storage, their effect in transfusion practise and strategies to minimize them.
leucodepletion is the removal of 99% leucocytes from the whole blood, pcv or platelets before transfusing into the donor.
this process many infections, transfusion reactions..
Red cell and platelet storage lesions and their effect in transfusion practiseArjuna Samaranayaka
Bio mechanical and metabolic changes that occur in red cell concentrates and platelets during ex-vivo storage, their effect in transfusion practise and strategies to minimize them.
This presentation describes the blood components. It also describes the problems in storing those component and what methods are used to overcome them.
Current Component Therapy by Diane Eklund, MDbloodbankhawaii
Lorem ipsum dolor sit amet, voluptaria percipitur has eu. Nibh iriure nostrud ei mea. Vel dicta voluptua convenire ei, id pro libris viderer. Pri et legendos atomorum, vel eu noster probatus menandri. Omnes possim ut eam, sed ea labore maiorum.
This presentation describes the blood components. It also describes the problems in storing those component and what methods are used to overcome them.
Current Component Therapy by Diane Eklund, MDbloodbankhawaii
Lorem ipsum dolor sit amet, voluptaria percipitur has eu. Nibh iriure nostrud ei mea. Vel dicta voluptua convenire ei, id pro libris viderer. Pri et legendos atomorum, vel eu noster probatus menandri. Omnes possim ut eam, sed ea labore maiorum.
Hybridoma Technology ( Production , Purification , and Application ) Sakshi Ghasle
Hybridoma technology revolutionized the field of immunology by enabling the production of monoclonal antibodies with high specificity and affinity. This presentation delves into the principles of DNA hybridoma technology, highlighting its significance in antibody production, therapeutic applications, and biomedical research. Learn about the key steps involved in generating hybridomas, from immunization to antibody screening, and discover the potential of recombinant DNA techniques in enhancing antibody engineering. Whether you're a student, researcher, or industry professional, this overview will provide valuable insights into the innovative world of hybridoma technology."
Uncover the wide-ranging applications of monoclonal antibodies in areas such as cancer therapy, autoimmune diseases, infectious diseases, and beyond. Learn about the latest advancements in antibody engineering and the development of novel therapeutic modalities, including bispecific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors.
Whether you're a seasoned researcher or a newcomer to the field, this SlideShare presentation serves as a valuable resource for understanding the principles, techniques, and applications of hybridoma technology in modern biomedicine. Join a journey through the fascinating world of monoclonal antibodies and the groundbreaking science behind their creation.
Unlock the potential of hybridoma technology and propel your research to new heights. Dive into this SlideShare presentation now and explore the limitless possibilities of monoclonal antibody production with hybridoma technology.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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.
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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
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.
Follow us on: Pinterest
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
2. Problems related to transfusion of allogenic
blood
• Formation of alloantibodies
• Rh D incompatibility – 50% chance of developing antibodies
• Difficult in finding Rh D negative blood in Asian regions
• Chronic transfusion therapy – development of multiple alloantibodies –
difficulty in finding suitable blood
• Acute haemolytic transfusion reactions and other immune and non-
immune transfusion reactions
3. Bioengineering the red blood cell
• Currently, no satisfactory solutions exist to prevent or cost-effectively
treat blood group alloimmunization or to improve the inventory of
Rh(D)− blood.
• Covalent grafting of biocompatible polymers to donor RBC has been
proposed to immunocamouflage the allogeneic RBCs
• Immunocamouflaged (stealth) RBC is manufactured by the covalent
grafting of methoxypoly(ethylene glycol) [mPEG; PEGylation], as well
as other polymers (e.g., polyoxazolines, POZ; and hyperbranched
polyglycerols, HPG), to membrane proteins on the surface of
allogeneic donor RBC
4.
5. • chemically activated polymers are covalently grafted to proteins at
exposed lysine residues
• grafted polymer, donor blood group antigens are biophysically and
immunologically masked while the modified RBC remaining
biologically and functionally viable.
6. Immunocamouflage technology in transfusion
medicine
1. Derivatize RBC to diminish transfusion reactions arising from
mismatched blood or alloimmunization
2. Utilization by clinical blood banks to camouflage the Rh(D) antigen
to improve blood inventories and utilization
3. Use of mPEG-modified RBC as a ‘chain-breaker’ (i.e., preventing RBC
aggregates arising from abnormal cell-cell interaction) in vascular
occlusive diseases such as sickle cell anemia
4. Prevention of transfusion-associated graft-versus-host disease.
7. Biophysical and biological characterization of
the stealth RBC
• Immunocamouflage of cells is a function of the biophysical and
biochemical nature of the grafted polymer
• grafted polymers confer its immunoprotective effects via
• steric hindrance
• charge camouflage
• The efficacy of membrane immunocamouflage is dependent upon both the
density (i.e., how much) and depth (i.e., thickness; polymer molecular
weight) of the polymer layer.
• Steric hindrance arises from either the rapid mobility arising from intra-
molecular flexibility of the polymer (mPEG and PEOZ) and/or polymer
density itself (HPG)
• Charge camouflage arises from polymer-mediated extension of the shear
plane (SP) thereby decreasing the apparent surface charge
8.
9. Manufacturing the ‘stealth RBC’
• On demand manufacturing of the stealth RBC will be the most likely
scenario.
• The manufacturing process of the stealth RBC is rapid and
straightforward and requires no specialized equipment
• The key tenet of the manufacturing process is the maintenance of a
constant polymer:cell ratio in order to achieve a homogenous grafting
of the polymers to the individual cells
10. • To achieve the homogeneity necessary for a clinical mPEG-RBC unit
two scalable devices utilizing micro-mixing chambers (alternatively Y-
connectors to induce turbulence and mixing) have been designed,
constructed and validated to semi-automate the RBC derivatization
process and minimize the risk of contamination.
• Using modifications of existing blood bags and sterile docking devices.
• Syringe Pump Method
• Peristaltic Pump Method
11.
12.
13.
14. Evaluating the potential clinical utility of the
stealth RBC
• Evaluating the potential efficacy of the stealth cell in the individual patient
is needed – for single antigen diversity of antibodies are developed by
individuals
• Large number of commercial testing protocols employ PEG (as either a
listed or unlisted ingredient) as a component of the testing reagents. The
reagent PEG will cause the mPEG-RBC to segregate as ‘PEG likes PEG’
• Slandered serological testing is not adequate to assess stealth RBCs.
• definitive testing approach for the potential clinical value of the stealth RBC
is the monocyte-monolayer assay (MMA). The MMA assesses FcγR-
mediated adherence and phagocytosis of alloantibody-opsonized donor
RBC by monocytes and has been clinically correlated with in vivo
transfusion safety
15. Institutional and governmental approval for
patient use
• Prior to the actual clinical use of the stealth RBC in a seriously ill patient,
compassionate use approval must be obtained from both the hospital
Research Ethics Board (REB; or equivalent) and the appropriate
governmental agencies
• One question likely to be raised by the REB is whether the proposed mPEG-
dosing is safe. The answer to this important question is, at least in part,
addressed by recent Phase I–III clinical trials of PEGylated human
haemoglobin (PEG-Hb; Sangart, San Diego, CA, USA).
• These clinical trials have infused humans, at the highest dosing schedule,
with up to 8.33 ml/kg of PEG-Hb. At this dosing, the typical male volunteers
(180 lbs/81.8 kg) received 680 ml of the PEG-Hb solution as a single dose,
an infusion of ~25 g of PEG. Importantly, no adverse effects were noted in
any of the human volunteers receiving this dose.
16. Conclusion
• Grafting of immunologically ‘inert’ polymers to the membrane of
allogeneic RBC can effectively camouflage non-ABO antigens from
immune recognition.
• These immunocamouflaged (i.e., stealth) RBCs may be an effective
tool in
• both preventing and treating alloimmunization in the chronically transfused
patient
• the transfusion of individual patients with rare blood phenotypes
• for emergency situation or geographic locations (e.g., China) where RhD-
negative blood is unavailable.
17. Conclusion
• Several characteristics of the immunocamouflaged RBC may also
make them highly suitable in patients/diseases characterized by RBC-
mediated vaso-occlusive events (e.g., sickle cell) consequent to the
polymer-mediated reduction in low-shear viscosity.
• Immunocamouflaged RBCs are inexpensively and easily manufactured
using commonly available equipment and existing blood bags.
• Potential clinical utility of the stealth RBC can be evaluated for the
individual patient using the clinically validated monocyte-monolayer
assay in which antigen-mismatched RBCs are PEGylated and then
opsonized with the patient’s own alloantibody.
18. Reference
• Immunocamouflaged RBC for Alloimmunized Patients
• By Mark D. Scott, Wendy M. Toyofuku, Xining Yang, Meera Raj and
Ning Kang
• Submitted: November 22nd 2016Reviewed: March 20th
2017Published: July 5th 2017
• DOI: 10.5772/intechopen.68647
Biophysical mechanisms of immunocamouflage. Panels A and B: Prevention of plasma protein (e.g., immunoglobulins) interaction with the cell membrane is due to both steric exclusion (shaded areas induced by the polymers radius of gyration; RF: Flory radii is the root mean square of end-to-end length of the polymer chain) and surface charge camouflage. The effects of both short chain (Panel A) and long chain (Panel B) polymers on the immunocamouflage of surface proteins (X, Y, Z) are schematically shown. The steric effect is maximized when chains are grafted at higher density, that is, with small separation between the chains (d). Importantly, antibody-antigen interaction is, biophysically speaking, charge-mediated. Membrane surface charge camouflage is primarily driven by polymer-mediated extension of the shear plane (SP) toward a region of decreased surface potential (Surface Potential Gradient). In the absence of polymer, the inherent shear plane (SP) of a cell is typically located 1–3 nm above the surface. The extension of SP is proportional to the hydrodynamic thickness of the polymer layer, which in turn is governed by the RF of the grafted polymer. Thus, 20 kDa polymers (large RF; Panel B) provide improved charge camouflage over 2 kDa polymers (small RF; Panel A). Delta (Δ) is the difference in the surface potential at the shear plane of a particle modified with the short (∆1) versus the long polymer (∆2). The membrane proteins X, Y and Z denote blood group antigens extending different distances from the cell surface. Panel C: Not all proteins in the complex topology of the RBC are equally accessible to grafting by the activated polymer, due to either its location in the protein complex or the paucity of lysines (the grafting site of activated mPEG). For example, Rh(D) is deeply buried in the complex while Kell is easily accessible. Thus, indirect immunocamouflage maybe more critical than direct immunocamouflage (i.e., direct modification of Rh(D) by mPEG) for many blood group antigens. Modified from Refs.