Screening Methods for behavioural and muscle Coordinationpradnya Jagtap
Screening Methods for behavioural and muscle Coordination
A. Motor activity and behaviour
1. Method of intermittent observation
2.Open field test
3.Hole board test
4.Combined open field test
B.Test for muscle coordination
1.Inclined plane method
2.Chimny test
3.Grip strength
4.Rotarod method
Screening Methods for behavioural and muscle Coordinationpradnya Jagtap
Screening Methods for behavioural and muscle Coordination
A. Motor activity and behaviour
1. Method of intermittent observation
2.Open field test
3.Hole board test
4.Combined open field test
B.Test for muscle coordination
1.Inclined plane method
2.Chimny test
3.Grip strength
4.Rotarod method
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
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
Preclinical Screening for Neurodegenerative Disease (Parkinsonism)Drx Burade
This file includes the general introduction of Parkinson's, sign and symptoms of Parkinson's, treatment of Parkinson's and the main content that is the Preclinical Screening models for Neurodegenerative disease like Parkinson's
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
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
Preclinical Screening for Neurodegenerative Disease (Parkinsonism)Drx Burade
This file includes the general introduction of Parkinson's, sign and symptoms of Parkinson's, treatment of Parkinson's and the main content that is the Preclinical Screening models for Neurodegenerative disease like Parkinson's
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxGautamSosa
Neurodegenerative diseases are conditions where nerve cells in the brain and peripheral nervous system gradually degenerate and die, leading to cognitive decline, movement disorders, and sometimes death. Examples include Alzheimer's, Parkinson's, multiple sclerosis and Huntington's disease. Treatment focuses on symptom management, as there are currently no cures for these conditions. Efficacy evaluation of any drug for Alzheimer's, Parkinson's, and multiple sclerosis in in-vivo animal studies, first step is to learn the in-vivo screening model of particular disease.
The current slide focuses on different screening models for neurodegenerative diseases along with a brief description of the diseases where the slides are to the points and brief with detailed evaluation.
Dietary Administration of Diquat for 13 Weeks Does Not Result in a Loss of Do...EPL, Inc.
Dietary Administration of Diquat for 13 Weeks Does Not Result in a Loss of Dopaminergic Neurons in the Substantia Nigra Pars Compacta (SNpc) of C57BL/6J Mice
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
1. SCREENING METHODS OF PARKINSON’S DISEASE
M. Pharm. (PTSM-1)
PRESENTED BY
NEERAJ RANA
NOIDA INSTITUTE OF ENGINEERING AND TECHNOLOGY
(PHARMACY INSTITUTE) GREATER NOIDA
Under Guidance:
Dr. Saumya Das
Associate Professor
2. OUTLINE
• Introduction
• Etiology
• Pathophysiology
• Classification
• In Vivo preclinical
• In Vitro preclinical Methods
• Gap of the study
• References
M. Pharm. (PTSM-1)
3. INTRODUCTION
Parkinson's disease (PD), which is the second most common
neurodegenerative disorder after Alzheimer's disease, is firstly defined after
James Parkinson.
M. Pharm. (PTSM-1)
4. PATHOPHYSIOLOGY
Parkinson's disease is primarily
associated with the gradual loss
of cells in the substantia nigra of
the brain. This area is responsible
for the production of dopamine.
Dopamine is a chemical
messenger that transmits signals
between two regions of the brain
to coordinate activity.
5. ETIOLOGY
The etiology of Parkinson's
disease (PD) has long been
thought to involve both
genetic and environmental
factors, but until recently
there has been no direct
evidence to support either
one as a causative factor.
However, in the past 8 years
six different genes have been
identified as causing familial
PD.
8. SCREENING MODELS
IN VIVO METHODS
• Tremorineand Oxotremorine Antagonism
• MPTP Model Of Parkinson’s Disease
• Reserpine Antagonism
• Circling Behavior In Nigrostriatal Lesioned Rats
• Elevated Body Swing Test
• Skilled Paw Reaching In Rats
• Stepping Test In Rats
• Gait Analysis
• Rotenone Induced Parkinson’s
M. Pharm. (PTSM-1
9. TREMORINE AND EXOTREMORINE
ANTAGONISM
• PURPOSE AND RATIONALE
• The muscranic agonists Tremaine and oxotremorine
induce parkinsonism-like signs such as tremor,
ataxia, spasticity, salivation, lacrimation and
hypothermia.
• These signs are antagonized by anticholinergic
drugs.
PROCEDURE
Groups of 6-10 male NMRI mice weighing 18-22g are used.
They are dosed orally with the test compound or the standard ( 5
mg/kg benzatropine mesilate) 1 h prior the administration of 0.5
mg/kg oxotremorine s.c.
10. • Rectal temperature is measured before
administration of the compound (Basal value) and
1,2and 3 h after oxotremorine injection.
Tremor is scored after oxotremorine dosage in 10 s
observation periods every 15 min for 1 h.
Tremor Score
Absent 0
Slight 1
Medium 2
Severe 3
M. Pharm. (PTSM-1
11. • Salivation and Lacrimation are scored 15 and 30 min
after oxotremorine injection.
Absent 0
Slight 1
Medium 2
Severe 3
EVALUATION
Hypothermia
The differences of the body temperature after 1,2 and 3
h versus basal values are summarized for each animals
in the control groups.
The average values are compared statistically.
12. • The scores for all animals in each group at the 3
observation periods are summarized.
The numbers in the treated groups are expressed as
percentage of the number of the control group.
Salivation and Lacrimation
The scores for the both symptoms for all animals in
each group are summarized at the 2 observation
periods.
The numbers in the treated groups are expressed as
percentage of the number of the control group
TREMOR
M. Pharm. (PTSM-1
13. MODIFICATIONS OF THE METHOD
• Johnson et al. (1986)
Developed a procedure for quantifying whole body tremors
in mice.
Displacement of a free floating platform by animal
movement created a change in resistance across a strain
gauge.
Administration of oxotremorine, 2.5 mg/kg i.p. produced
numerous high – frequency, high intensity peaks within 5
min.
M. Pharm. (PTSM-1
14. • Clement and Dyck (1989)
Constructed and tested a tremor monitor that quantitates
soma and oxotremorine induced tremors.
The device consisted of a force transducer, from which a
plastic beaker was suspended containing a mouse.
The signal from the force transducer was fed into a tremor
monitor and quantitated using the Applecounter from
Columus Instruments.
Coward et al. (1977)
Recommended N- carbamoyl-2- (2,6-dichlorophenyl)
acetamidine hypo chloride (LON-1954), a tremor genic
agent, as alternative to oxotremorine for the detection of
anti Parkinson drugs.
15. B. MPTP model in Monkeys
• PURPOSE AND RATIONALE
N- MPTP ( N-methyl-4-phenyl-1,2,3,6-
tetrahydopyridine) has been shown to cause
symptoms of Parkinson’s disease in exposed
individuals.
When administered to primates this compound
causes a partial destruction of basal ganglia and a
syndrome that resembles Parkinson’s diseases.
M. Pharm. (PTSM-1
16.
17. PROCEDURE
• Burns et al. (1983) treated 8 adult rhesus monkeys
weighing 5-8 kg over a period of 5-8 days with cumulative
intravenous doses of N-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (N-MPTP) up to 10-18 mg/kg.
These animals showed a parkinsonism like disorder
(Drooling, rigidity, akinesia, postural tremors), which was
reversed by the administration of L-dopa.
The pathological and biochemical changes produced by N-
MPTP are similar to the well established changes in
patients in patients with Parkinsonism.
M. Pharm. (PTSM-1
19. MODIFICATIONS OF THE METHOD
• Kebanian et al. (1992) tested a selective D1 receptor agonist
with antiparkinsonian activity in MTPT treated marmosets.
Domino and Sheng (1993) studied the relative potency of some
dopamine agonists with varying selectivities for D1 and D2
receptors in MPTP induced hemiparkinsonian monkeys.
Asin et al. (1997) tested a selective D1 receptor agonist in rats
previously given unilateral 6 hydroxydopamine injections and in
macaques previously given unilateral, intracarotid infusions of
MPTP.
M. Pharm. (PTSM-1
21. SCREENING MODELS
IN VITRO METHODS
• Experiment Using Rat Strial Slices
• Dopamine Stimulated Adenyl Cyclase Activity
• Culture Of Substantial Nigra
• Inhibition of Apoptosis In Neuroblastoma SH-SY5Y
Cells
• Radioligant Binding Studies For D1 And D2 Dopamine
Receptor
• In Vitro Neuroprotective Efficacy
M. Pharm. (PTSM-1
22. Experiment Using Rat Strial Slices
• Striatum in brain is primarily affected in parkinsonism.
The release of the neurotransmitter like dopamine and
acetylcholine in response to test agent serve as a good
in vitro marker of its activity.Male spargue dawley
rats(150-250g)are decapitated,the skull is opened.
• Right and left striata are removed & placed in ice-cold
Krebs solution.
• The striata is cut into 0.4mm thick slices using a tissue
chopper.
23. • The slices are kept floating for 30 min in Krebs solution &
gassed with 95% O2 & 5% Co2 at room temperature.
• The slices are labelled by incubating for 30 min at 37C
with[3H] dopamine (5ml) & [14c] choline (2ml) in the
presence of 0.15mM pargyline chloride & 0.1 mm ascorbic
acid.
• Labeled slices are transferred to superfusion chambers &
perfused with Krebs solutions at 37C at flow rate of
0.5ml/min.
• After washing & stabilization 5 min fraction of superfast
are collected.
24. • The perfusion buffer contains 1µM nomifensine to
inhibit dopamine reuptake & 10µM hemicholinium to
inhibit choline uptake.
• The slices are subjected to field strength to the current
strength of 10-15mA/cm2 & pulse duration of 2msec at
stimulation frequency of 3 Hz for 5 min.
• Drugs to be tested are percent in the superfusion fluid
25. • The radioactivity in the superfast samples & in the
tissue is determined by liquid scintillation counting.
• The radiolabelled choline method makes it possible to
study Ach release in vitro without inhibiting
cholinesterase, thus minimizing auto inhibition of
transmitter release caused by accumulation of
unhydrolised of Ach.
M. Pharm. (PTSM-1
26. DOPAMINE STUMILATED ADENYLY CYCLASE
ACTIVITY
• Male sprege dawlety (150-250) are decapitated and left
striata are removed
• Striatal tissue homogenized in chilled buffer containing
10mm imidazole, 2mm EDTA and 10% source ph 7.3
• Homogenate is centrifuged at thousand g for 10min and
supernatant is recentifuged at 27000g for 20min
27. • The pellet obtained is washed twice and suspended in
10mM imidazole pH. 7.3 membrane prate is determine by
Bradford's method using bovine serum
• Adenylyl cycles activity is measured by calculating the
conversion rate of (32p) ATP to (32p) cAMP
• The assay is perform in 250microaL solution containing
imidazole ,mgcl2 papaverine dithiothretol
ATP,GTP,phosphokinase
28. • The reaction mixture is preincubate at 30c for 5min the
reaction is initiated by adding membrane proteins and
incubated for 10min
• The reaction is terminated by adding stopping solution
(ATP,SDS,cAMP). Formed (32p)cAMP is separated
from(32P)ATP by chromatography.
M. Pharm. (PTSM-1
29. GAP OF THE STUDY
The major gap of the studies is scientists could not have
found exact approaches to cure this disease.
M. Pharm. (PTSM-1)
30. REFERENCE
•A. Schrage, P. Barone, R. G. Brown et al., “Depression rating scales
in Parkinson’s disease: critique and recommendations,” Movement
Disorders, vol. 22, no. 8, pp. 1077–1092, 2007.
•A. F. G. Lenten's, K. Dujardin, L. Marsh et al., “Apathy and anhedonia
rating scales in Parkinson’s disease: critique and recommendations,”
Movement Disorders, vol. 23, no. 14, pp. 2004–2014, 2008.
•H. F. Kaiser, “An index of factorial simplicity,” Psychometrical, vol. 39,
no. 1, pp. 31–36, 1974.
•F. Raudino, “Non motor off in Parkinson’s disease,” Acta Neurological
Scandinavia, vol. 104, no. 5, pp. 312–315, 2001.