The document summarizes recent advances in understanding and treating Alzheimer's disease. It discusses both non-modifiable and modifiable risk factors for the disease. The major signs and symptoms include progressive memory loss and cognitive decline. Alzheimer's is confirmed through neuronal plaques and tangles seen in the brain. Recent treatment strategies aim to reduce amyloid plaques through vaccines, antibodies, and inhibitors of beta- and gamma-secretase. Other approaches include tau phosphorylation inhibitors, therapies for mitochondrial dysfunction, and cholinesterase inhibitors. Animal models continue to be important for studying the human APP, ApoE, and presenilin genes involved in Alzheimer's pathology.
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
Free radicals are highly reactive molecules that can damage cells. The field of free radical pharmacology studies how free radicals influence health and disease, and how antioxidants may help reduce oxidative stress. Research suggests free radicals play a role in aging and diseases like cancer, while antioxidants in fruits and vegetables may help counter the effects of free radicals in the body.
test item characterization of regulatory of toxicological studies SonaliJain736101
This document provides guidance on characterizing test items used in regulatory toxicology studies conducted in compliance with Good Laboratory Practice principles. It discusses the expectations for characterizing test items regarding transportation, receipt, identification, labeling, sampling, handling, storage, and disposal. The level of characterization may vary depending on the test item, study objectives, and development stage. Characterization should confirm the test item's identity and suitability for the study. Living organisms and medical devices may require unique characterization information. The document aims to promote a consistent approach to test item characterization across studies.
IND (Investigational New Drug) industrial perspectiveAYESHA NAZEER
Describing the Industry's/sponsor's/drug manufacturers' perspective of the Investigational New Drug Application (IND) program based on the survey conducted by the Office Of Inspector General (OIG).
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
The document summarizes recent advances in understanding and treating Alzheimer's disease. It discusses both non-modifiable and modifiable risk factors for the disease. The major signs and symptoms include progressive memory loss and cognitive decline. Alzheimer's is confirmed through neuronal plaques and tangles seen in the brain. Recent treatment strategies aim to reduce amyloid plaques through vaccines, antibodies, and inhibitors of beta- and gamma-secretase. Other approaches include tau phosphorylation inhibitors, therapies for mitochondrial dysfunction, and cholinesterase inhibitors. Animal models continue to be important for studying the human APP, ApoE, and presenilin genes involved in Alzheimer's pathology.
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
Free radicals are highly reactive molecules that can damage cells. The field of free radical pharmacology studies how free radicals influence health and disease, and how antioxidants may help reduce oxidative stress. Research suggests free radicals play a role in aging and diseases like cancer, while antioxidants in fruits and vegetables may help counter the effects of free radicals in the body.
test item characterization of regulatory of toxicological studies SonaliJain736101
This document provides guidance on characterizing test items used in regulatory toxicology studies conducted in compliance with Good Laboratory Practice principles. It discusses the expectations for characterizing test items regarding transportation, receipt, identification, labeling, sampling, handling, storage, and disposal. The level of characterization may vary depending on the test item, study objectives, and development stage. Characterization should confirm the test item's identity and suitability for the study. Living organisms and medical devices may require unique characterization information. The document aims to promote a consistent approach to test item characterization across studies.
IND (Investigational New Drug) industrial perspectiveAYESHA NAZEER
Describing the Industry's/sponsor's/drug manufacturers' perspective of the Investigational New Drug Application (IND) program based on the survey conducted by the Office Of Inspector General (OIG).
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
1) Digoxin immunoassay is used to monitor digoxin levels in patients' serum since digoxin has a narrow therapeutic range and toxic levels can mimic disease symptoms.
2) Various analytical methods are used for digoxin immunoassay including radioimmunoassay, enzyme immunoassay, cloned enzyme donor immunoassay, fluorescence polarization immunoassay, and enzyme multiplied immunoassay.
3) The general procedure involves adding patient serum, labeled digoxin tracer, and antibody to wells before incubating and measuring enzyme activity, with the activity inversely proportional to digoxin concentration in the patient's serum sample.
The document summarizes the immune system and how it distinguishes self from nonself through innate and adaptive immunity. It then discusses immunomodulators which can suppress or stimulate the immune response, dividing them into immunosuppressants and immunostimulants. Several screening methods for evaluating immunomodulatory activity are also presented, including acute systemic anaphylaxis in rats, anti-anaphylactic activity, passive cutaneous anaphylaxis, Arthus type hypersensitivity, delayed type hypersensitivity, and carbon clearance tests for phagocytic response measurement. Modifications to these screening methods are also noted.
Toxicokinetic evaluation in preclinical studies.pptxashharnomani
Toxicokinetic studies aim to understand what the body does with a drug at high doses. Such studies measure parameters like maximum plasma concentration, time to maximum concentration, and area under the plasma concentration curve. Toxicokinetic data from preclinical studies can be used to select appropriate doses and dosing routes for clinical trials and to interpret toxicity findings. Factors like protein binding, metabolism, and species differences must be considered when evaluating toxicokinetic data.
1) The document discusses various in vitro and in vivo models used to study immunomodulatory activity, including inhibition of histamine release from mast cells, lymphocyte proliferation assays, and animal models of autoimmune diseases and hypersensitivity reactions.
2) Test protocols are provided for studying immunomodulation using assays such as mixed lymphocyte reactions, lymphocyte stimulation and cytokine production.
3) Animal models described include adjuvant-induced arthritis in rats and various spontaneous autoimmune disease models in mice and other species. Standard protocols are given for evaluating compounds in these disease models.
Alternative methods to animal toxicity testingpriyachhikara1
This document discusses alternative methods to animal toxicity testing, including in silico computer simulation methods, in vitro cell culture techniques, using fewer animals, microdosing, and epidemiological and clinical studies. It provides details on regulatory agencies that promote alternative testing methods, as well as specific alternative tests that have been developed and validated according to OECD guidelines to replace or reduce animal use.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
Recent advancement in parkinson's diseaseRajesh Yadav
The document discusses recent advancements in Parkinson's disease. It provides an introduction to Parkinson's, including its symptoms and characteristics like dopamine neuron loss. It then outlines current drug treatments that act on the dopaminergic and cholinergic systems, such as Levodopa. New drug treatments and surgical options like deep brain stimulation are also discussed. The document concludes by mentioning gene therapy and stem cell therapy as potential future treatment methods.
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Preclinical studies involve testing drugs or treatments in animals before human trials. This document discusses various types of preclinical studies including in vitro, in vivo, in situ, and in silico experiments. It also describes methods to study immunomodulators including inhibition of histamine release from mast cells and mitogen-induced lymphocyte proliferation assays. Various in vivo models are outlined such as acute systemic anaphylaxis in rats and delayed type hypersensitivity tests.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
Introduction to Screening Models of Hepatoprotective Drugs
Liver toxicity, Drugs causing DILI, Markers of hepatotoxicity
List of hepatoprotectives, Functions of liver
Screening models of hepatoprotective drugs
Presented by
I. Sai Reddemma
Department of Pharmacology
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
This document discusses the immunoassay of insulin. It begins with introducing immunoassays and their principle of competitive binding between labeled and unlabeled analytes for antibody binding sites. It describes the key reagents of antigens, antibodies, signal-generating labels, and separation matrices. The document then focuses on insulin as the analyte and outlines the specific procedure for its immunoassay, including using guinea pigs to produce antibodies, running standards and samples in assays, and evaluating the results against a standard curve to determine insulin concentrations.
Cellular and Biochemical mediators of Inflammation and Immune.pptxDinamGyatsoAadHenmoo
This document summarizes cellular and biochemical mediators of inflammation and immune response. It describes:
1) Cell-derived mediators including vasoactive amines, arachidonic acid metabolites, lysosomal components, platelets activating factors, and cytokines.
2) Plasma-derived mediators including the kinin system, clotting system, fibrinolytic system, and complement system.
3) The roles and actions of key mediators like histamine, serotonin, prostaglandins, leukotrienes, nitric oxide, complement proteins, and cytokines in modulating inflammation and immune response.
Role Of Transgenic Animal In Target Validation-1.pptxNikitaBankoti2
A Transgenic animal is one that carries a foreign gene that has been deliberately inserted into its genome.
The foreign gene are inserted into the germ line of the animal, so it can be transmitted to the progeny.
Transgenic animals are animals that are genetically altered to have traits that mimic symptoms of specific human pathologies.
They provide genetic model of various human disease which are important in understanding disease and development of new target.
This document discusses screening methods for antihypertensive agents. It begins with an introduction on hypertension and its prevalence. It then discusses various animal models used to study hypertension including spontaneous hypertensive rats. It provides details on several in vivo and in vitro screening models for inducing and studying hypertension including acute renal hypertension in rats, chronic renal hypertension in rats and dogs, and genetic hypertension in rats. It describes procedures, evaluations, and modifications of these methods. The goal is to utilize animal models that replicate features of human hypertension to screen for new antihypertensive agents.
This document outlines objectives and principles of safety pharmacology studies. It discusses using such studies to protect clinical trial participants from potential adverse drug effects. The document describes the scope of safety pharmacology, considerations for test systems and study design, and examples of core safety pharmacology assessments of the central nervous, cardiovascular and respiratory systems. Evaluation methods are also summarized for each system. The document concludes by listing some references on safety pharmacology guidelines.
Alzheimer's disease is a progressive brain disorder that destroys memory and thinking skills. The document discusses the risk factors, symptoms, pathogenesis, therapeutic targets, and treatment of Alzheimer's disease. It summarizes that current therapies can temporarily ease symptoms but effective disease-modifying drugs are still being researched as the pathogenesis is complex, involving both genetic and environmental factors.
1) Digoxin immunoassay is used to monitor digoxin levels in patients' serum since digoxin has a narrow therapeutic range and toxic levels can mimic disease symptoms.
2) Various analytical methods are used for digoxin immunoassay including radioimmunoassay, enzyme immunoassay, cloned enzyme donor immunoassay, fluorescence polarization immunoassay, and enzyme multiplied immunoassay.
3) The general procedure involves adding patient serum, labeled digoxin tracer, and antibody to wells before incubating and measuring enzyme activity, with the activity inversely proportional to digoxin concentration in the patient's serum sample.
The document summarizes the immune system and how it distinguishes self from nonself through innate and adaptive immunity. It then discusses immunomodulators which can suppress or stimulate the immune response, dividing them into immunosuppressants and immunostimulants. Several screening methods for evaluating immunomodulatory activity are also presented, including acute systemic anaphylaxis in rats, anti-anaphylactic activity, passive cutaneous anaphylaxis, Arthus type hypersensitivity, delayed type hypersensitivity, and carbon clearance tests for phagocytic response measurement. Modifications to these screening methods are also noted.
Toxicokinetic evaluation in preclinical studies.pptxashharnomani
Toxicokinetic studies aim to understand what the body does with a drug at high doses. Such studies measure parameters like maximum plasma concentration, time to maximum concentration, and area under the plasma concentration curve. Toxicokinetic data from preclinical studies can be used to select appropriate doses and dosing routes for clinical trials and to interpret toxicity findings. Factors like protein binding, metabolism, and species differences must be considered when evaluating toxicokinetic data.
1) The document discusses various in vitro and in vivo models used to study immunomodulatory activity, including inhibition of histamine release from mast cells, lymphocyte proliferation assays, and animal models of autoimmune diseases and hypersensitivity reactions.
2) Test protocols are provided for studying immunomodulation using assays such as mixed lymphocyte reactions, lymphocyte stimulation and cytokine production.
3) Animal models described include adjuvant-induced arthritis in rats and various spontaneous autoimmune disease models in mice and other species. Standard protocols are given for evaluating compounds in these disease models.
Alternative methods to animal toxicity testingpriyachhikara1
This document discusses alternative methods to animal toxicity testing, including in silico computer simulation methods, in vitro cell culture techniques, using fewer animals, microdosing, and epidemiological and clinical studies. It provides details on regulatory agencies that promote alternative testing methods, as well as specific alternative tests that have been developed and validated according to OECD guidelines to replace or reduce animal use.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
Recent advancement in parkinson's diseaseRajesh Yadav
The document discusses recent advancements in Parkinson's disease. It provides an introduction to Parkinson's, including its symptoms and characteristics like dopamine neuron loss. It then outlines current drug treatments that act on the dopaminergic and cholinergic systems, such as Levodopa. New drug treatments and surgical options like deep brain stimulation are also discussed. The document concludes by mentioning gene therapy and stem cell therapy as potential future treatment methods.
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Preclinical studies involve testing drugs or treatments in animals before human trials. This document discusses various types of preclinical studies including in vitro, in vivo, in situ, and in silico experiments. It also describes methods to study immunomodulators including inhibition of histamine release from mast cells and mitogen-induced lymphocyte proliferation assays. Various in vivo models are outlined such as acute systemic anaphylaxis in rats and delayed type hypersensitivity tests.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
Introduction to Screening Models of Hepatoprotective Drugs
Liver toxicity, Drugs causing DILI, Markers of hepatotoxicity
List of hepatoprotectives, Functions of liver
Screening models of hepatoprotective drugs
Presented by
I. Sai Reddemma
Department of Pharmacology
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
This document discusses the immunoassay of insulin. It begins with introducing immunoassays and their principle of competitive binding between labeled and unlabeled analytes for antibody binding sites. It describes the key reagents of antigens, antibodies, signal-generating labels, and separation matrices. The document then focuses on insulin as the analyte and outlines the specific procedure for its immunoassay, including using guinea pigs to produce antibodies, running standards and samples in assays, and evaluating the results against a standard curve to determine insulin concentrations.
Cellular and Biochemical mediators of Inflammation and Immune.pptxDinamGyatsoAadHenmoo
This document summarizes cellular and biochemical mediators of inflammation and immune response. It describes:
1) Cell-derived mediators including vasoactive amines, arachidonic acid metabolites, lysosomal components, platelets activating factors, and cytokines.
2) Plasma-derived mediators including the kinin system, clotting system, fibrinolytic system, and complement system.
3) The roles and actions of key mediators like histamine, serotonin, prostaglandins, leukotrienes, nitric oxide, complement proteins, and cytokines in modulating inflammation and immune response.
Role Of Transgenic Animal In Target Validation-1.pptxNikitaBankoti2
A Transgenic animal is one that carries a foreign gene that has been deliberately inserted into its genome.
The foreign gene are inserted into the germ line of the animal, so it can be transmitted to the progeny.
Transgenic animals are animals that are genetically altered to have traits that mimic symptoms of specific human pathologies.
They provide genetic model of various human disease which are important in understanding disease and development of new target.
This document discusses screening methods for antihypertensive agents. It begins with an introduction on hypertension and its prevalence. It then discusses various animal models used to study hypertension including spontaneous hypertensive rats. It provides details on several in vivo and in vitro screening models for inducing and studying hypertension including acute renal hypertension in rats, chronic renal hypertension in rats and dogs, and genetic hypertension in rats. It describes procedures, evaluations, and modifications of these methods. The goal is to utilize animal models that replicate features of human hypertension to screen for new antihypertensive agents.
This document outlines objectives and principles of safety pharmacology studies. It discusses using such studies to protect clinical trial participants from potential adverse drug effects. The document describes the scope of safety pharmacology, considerations for test systems and study design, and examples of core safety pharmacology assessments of the central nervous, cardiovascular and respiratory systems. Evaluation methods are also summarized for each system. The document concludes by listing some references on safety pharmacology guidelines.
Alzheimer's disease is a progressive brain disorder that destroys memory and thinking skills. The document discusses the risk factors, symptoms, pathogenesis, therapeutic targets, and treatment of Alzheimer's disease. It summarizes that current therapies can temporarily ease symptoms but effective disease-modifying drugs are still being researched as the pathogenesis is complex, involving both genetic and environmental factors.
The document discusses Alzheimer's disease (AD), including its causes, symptoms, pathogenesis, and treatment approaches. It begins by defining AD as a progressive brain disease that destroys memory and cognitive abilities. Risk factors include age, family history, head trauma, and genetic factors. Symptoms start with mild memory loss and eventually lead to severe cognitive decline and inability for self-care. The pathogenesis involves beta-amyloid plaques and neurofibrillary tangles resulting from tau protein abnormalities. Current treatments target symptoms but not the underlying disease process, and focus on acetylcholinesterase inhibitors, memantine, vaccines, and antioxidants. Research continues on disease-modifying therapies such as inhibiting amyloid formation or tau phosphorylation.
Emerging Trends in Alzheimer’s Disease by Dr. Seema.pptDrSeemaBansal
Emerging Trends in Alzheimer’s Disease discusses the pathogenesis and treatment approaches for Alzheimer's disease (AD). There are currently medications to treat mild to moderate AD symptoms, while research explores new treatments. The document outlines several hypotheses for AD causes, including amyloid plaques, neurofibrillary tangles, and cholinergic dysfunction. Therapies target these pathways through secretase inhibitors, vaccines, and other methods. Epidemiological studies examine lifestyle factors that may influence AD risk or protection. Advances in diagnosis include neuroimaging and biomarkers to detect signs of AD earlier.
Alzheimer's disease is a progressive brain disorder that destroys memory and cognitive skills. Dr. Alois Alzheimer first described it in 1906 after examining a woman with dementia. The disease is characterized by beta-amyloid plaques and neurofibrillary tangles in the brain. Current treatments aim to improve symptoms but do not stop the underlying disease process. Researchers are exploring therapies targeting amyloid and tau proteins as well as other mechanisms to find a cure.
This document discusses mania and bipolar disorder. It defines mania as a mood disorder characterized by elevated mood, increased energy and activity levels, and other symptoms. Bipolar disorder involves alternating periods of mania and depression. The document outlines the diagnostic criteria for manic and hypomanic episodes. It explores the neurobiology of bipolar disorder including the involvement of neurotransmitter systems and cellular signaling pathways. Genes associated with bipolar disorder are also mentioned. The document discusses treatment options and provides tables on FDA-approved medications for managing different phases of bipolar disorder.
This document summarizes the molecular basis of Alzheimer's disease. It begins by describing Alzheimer's as a progressive neurodegenerative disorder characterized by memory loss and cognitive decline. Key pathological features are amyloid plaques and neurofibrillary tangles in the brain. The accumulation of these proteins is thought to lead to synaptic loss, neuronal death, and the cognitive symptoms of the disease. Current drug therapies can only temporarily improve symptoms but do not stop the underlying disease progression. Researchers are actively investigating strategies to modify the disease course by targeting amyloid production, clearance, or aggregation in the brain. While promising approaches are being studied, there are currently no approved disease-modifying treatments for Alzheimer's.
Treatment of schizophrenia current issues and future possibilitiesDr Wasim
The document discusses the evolution of treatments for schizophrenia from early interventions like insulin coma therapy to first-generation antipsychotics like chlorpromazine to newer second-generation drugs. It notes limitations of current antipsychotics in treating negative symptoms and cognitive impairment and side effects like weight gain. The document outlines several new approaches being explored, including modulating the glutamate system by targeting the glycine site on NMDA receptors with drugs like glycine or inhibiting glycine transporters, as well as targeting metabotropic glutamate receptors. Clinical trials are underway to evaluate potential cognitive-enhancing effects of these strategies.
Alzheimer disease , is there any hope for cureOsama Ragab
- Alzheimer's disease affects over 100 million people worldwide and is projected to increase significantly by 2050. While much research has focused on amyloid plaques and tau tangles as potential causes, treatments targeting these pathways have yet to successfully slow or stop the progression of the disease.
- Alternative hypotheses for Alzheimer's causation include neuroinflammation, oxidative stress, metabolic dysfunction, and aging. Strategies targeting these pathways also have not resulted in effective treatments.
- The exact causes and mechanisms of Alzheimer's remain unclear as amyloid and tau are normal brain proteins and their roles are still being understood. Further research is still needed to determine the root causes and identify effective treatments for this devastating disease.
Recent advances in neurodegenerative disorders.pptxSiddhartha Dutta
This document summarizes several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Wilson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. For each disease, it discusses characteristics, current treatments, and recent advances in pharmacotherapy. A variety of drug classes and mechanisms are covered, ranging from cholinesterase inhibitors and NMDA antagonists for Alzheimer's to dopamine agonists and MAO-B inhibitors for Parkinson's disease.
This document discusses an in silico study that screened six compounds (IQ3, echothiophate, 15d-PGJ2, mefenamic acid, phentolamine, and nateglinide) against four protein targets related to Alzheimer's disease (AChE, beta-secretase 1, C-Jun N-terminal kinase-3, and peroxisome proliferator-activated receptor γ) using molecular docking. Pharmacokinetic properties were also analyzed using software. The results suggested that IQ3, nateglinide, phentolamine, and mefenamic acid strongly bound to the selected AD targets based on docking scores. No ligands violated Lipinski's rules and all
This document describes an in silico study that screened six compounds (IQ3, echothiophate, 15d-PGJ2, mefenamic acid, phentolamine, and nateglinide) against four protein targets related to Alzheimer's disease (AChE, BACE1, JNK3, PPARγ) using molecular docking. Pharmacokinetic properties were also analyzed using pkCSM and SwissADME software. Molecular docking results found that IQ3, nateglinide, phentolamine, and mefenamic acid significantly interacted with the AD targets. All ligands were found to have blood-brain barrier permeability and intestinal absorption. Toxicity predictions showed some
This document discusses different types of autoimmune encephalitis. It categorizes autoimmune encephalitis as either paraneoplastic, non-paraneoplastic, or associated with vasculitis. Within non-paraneoplastic autoimmune encephalitis, several specific types are described that are associated with antibodies against receptors like NMDA, GABA, AMPA, and LGI1. Clinical features, pathogenesis, diagnosis and treatment approaches are summarized for several of these subtypes, with particular focus on anti-NMDA receptor encephalitis. Prognosis and potential neurologic sequelae are also briefly covered.
This document discusses different types of autoimmune encephalitis. It categorizes autoimmune encephalitis as either paraneoplastic, non-paraneoplastic, or associated with vasculitis. Within non-paraneoplastic autoimmune encephalitis, several specific types are described that are associated with antibodies against receptors like NMDA, GABA, AMPA, and LGI1. Clinical features, pathogenesis, diagnosis and treatment approaches are summarized for some of the major types like anti-NMDA receptor encephalitis. Long term management involves immunosuppression with steroids and other agents to prevent relapse, though neurologic sequelae may still occur in some patients.
This document discusses potential neuroprotective strategies for glaucoma. It begins by explaining that glaucoma involves the loss of retinal ganglion cells and their axons, and that while elevated intraocular pressure is a risk factor, progression can still occur when pressure is lowered. Neuroprotection aims to protect these cells from degeneration. Several potential neuroprotective approaches are then described, including NMDA antagonists to reduce excitotoxicity, anti-apoptotic agents to block cell death pathways, currently used drugs that may have neuroprotective effects, antioxidants to reduce free radicals, calcium channel blockers, neurotrophic factors, gene therapy targeting apoptotic factors, and immunomodulators.
Current management of alzheimer’s disease and amyloid peptidesDr Amit Mittal
Dr. Amit Mittal's document provides an overview of the current management of Alzheimer's disease and amyloid peptides. It discusses the pathology and clinical presentation of Alzheimer's, including memory loss and cognitive decline. Epidemiology statistics on the prevalence and worldwide burden of Alzheimer's are presented. The document reviews genetics, pathophysiology based on amyloid and tau proteins, diagnosis, and clinical assessment scales. Current drug treatments target cholinergic systems and NMDA receptors. Recent research focuses on preventing amyloid plaque and tau tangle formation through various mechanisms.
Neurodegenrative disorders by Dr Rbalaraman.pptxRBalaraman4
1. Neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and stroke result from neuronal death in the brain. The mechanisms of neuronal death include protein deposition, excitotoxicity, oxidative stress, and apoptosis.
2. While dead neurons cannot regenerate in the adult brain, pharmacological treatments can help prevent neuronal loss or compensate for it. Cholinesterase inhibitors are used for Alzheimer's disease and levodopa is used for Parkinson's disease.
3. Research is exploring new drug targets to stop the molecular pathways leading to neuronal death in these disorders, with the goal of developing disease-modifying treatments in the future.
The document discusses Alzheimer's disease (AD), which causes neurodegeneration and is the main cause of dementia. AD affects around 40 million people globally and is expected to impact over 100 million by 2050. Current treatments for AD symptoms include cholinesterase inhibitors, NMDA receptor antagonists, and combination therapy. Emerging therapies target amyloid proteins, tau proteins, and neuroinflammation. Drug repurposing is also a strategy being used, with 40% of drugs in AD clinical trials being repurposed compounds. The document outlines various therapeutic targets in AD treatment including secretases, neuroinflammation, tau deposition, amyloid antibodies, and stem cell therapy. Epigenetics is also discussed as a potential therapeutic target for AD.
Similar to Recent advances in Alzheimer's disease.pptx (20)
Embracing Deep Variability For Reproducibility and Replicability
Abstract: Reproducibility (aka determinism in some cases) constitutes a fundamental aspect in various fields of computer science, such as floating-point computations in numerical analysis and simulation, concurrency models in parallelism, reproducible builds for third parties integration and packaging, and containerization for execution environments. These concepts, while pervasive across diverse concerns, often exhibit intricate inter-dependencies, making it challenging to achieve a comprehensive understanding. In this short and vision paper we delve into the application of software engineering techniques, specifically variability management, to systematically identify and explicit points of variability that may give rise to reproducibility issues (eg language, libraries, compiler, virtual machine, OS, environment variables, etc). The primary objectives are: i) gaining insights into the variability layers and their possible interactions, ii) capturing and documenting configurations for the sake of reproducibility, and iii) exploring diverse configurations to replicate, and hence validate and ensure the robustness of results. By adopting these methodologies, we aim to address the complexities associated with reproducibility and replicability in modern software systems and environments, facilitating a more comprehensive and nuanced perspective on these critical aspects.
https://hal.science/hal-04582287
Compositions of iron-meteorite parent bodies constrainthe structure of the pr...Sérgio Sacani
Magmatic iron-meteorite parent bodies are the earliest planetesimals in the Solar System,and they preserve information about conditions and planet-forming processes in thesolar nebula. In this study, we include comprehensive elemental compositions andfractional-crystallization modeling for iron meteorites from the cores of five differenti-ated asteroids from the inner Solar System. Together with previous results of metalliccores from the outer Solar System, we conclude that asteroidal cores from the outerSolar System have smaller sizes, elevated siderophile-element abundances, and simplercrystallization processes than those from the inner Solar System. These differences arerelated to the formation locations of the parent asteroids because the solar protoplane-tary disk varied in redox conditions, elemental distributions, and dynamics at differentheliocentric distances. Using highly siderophile-element data from iron meteorites, wereconstruct the distribution of calcium-aluminum-rich inclusions (CAIs) across theprotoplanetary disk within the first million years of Solar-System history. CAIs, the firstsolids to condense in the Solar System, formed close to the Sun. They were, however,concentrated within the outer disk and depleted within the inner disk. Future modelsof the structure and evolution of the protoplanetary disk should account for this dis-tribution pattern of CAIs.
TOPIC OF DISCUSSION: CENTRIFUGATION SLIDESHARE.pptxshubhijain836
Centrifugation is a powerful technique used in laboratories to separate components of a heterogeneous mixture based on their density. This process utilizes centrifugal force to rapidly spin samples, causing denser particles to migrate outward more quickly than lighter ones. As a result, distinct layers form within the sample tube, allowing for easy isolation and purification of target substances.
JAMES WEBB STUDY THE MASSIVE BLACK HOLE SEEDSSérgio Sacani
The pathway(s) to seeding the massive black holes (MBHs) that exist at the heart of galaxies in the present and distant Universe remains an unsolved problem. Here we categorise, describe and quantitatively discuss the formation pathways of both light and heavy seeds. We emphasise that the most recent computational models suggest that rather than a bimodal-like mass spectrum between light and heavy seeds with light at one end and heavy at the other that instead a continuum exists. Light seeds being more ubiquitous and the heavier seeds becoming less and less abundant due the rarer environmental conditions required for their formation. We therefore examine the different mechanisms that give rise to different seed mass spectrums. We show how and why the mechanisms that produce the heaviest seeds are also among the rarest events in the Universe and are hence extremely unlikely to be the seeds for the vast majority of the MBH population. We quantify, within the limits of the current large uncertainties in the seeding processes, the expected number densities of the seed mass spectrum. We argue that light seeds must be at least 103 to 105 times more numerous than heavy seeds to explain the MBH population as a whole. Based on our current understanding of the seed population this makes heavy seeds (Mseed > 103 M⊙) a significantly more likely pathway given that heavy seeds have an abundance pattern than is close to and likely in excess of 10−4 compared to light seeds. Finally, we examine the current state-of-the-art in numerical calculations and recent observations and plot a path forward for near-future advances in both domains.
PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
Anti-Universe And Emergent Gravity and the Dark UniverseSérgio Sacani
Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
BIRDS DIVERSITY OF SOOTEA BISWANATH ASSAM.ppt.pptxgoluk9330
Ahota Beel, nestled in Sootea Biswanath Assam , is celebrated for its extraordinary diversity of bird species. This wetland sanctuary supports a myriad of avian residents and migrants alike. Visitors can admire the elegant flights of migratory species such as the Northern Pintail and Eurasian Wigeon, alongside resident birds including the Asian Openbill and Pheasant-tailed Jacana. With its tranquil scenery and varied habitats, Ahota Beel offers a perfect haven for birdwatchers to appreciate and study the vibrant birdlife that thrives in this natural refuge.
1. RECENT ADVANCES IN TREATMENT OF
ALZHEIMER’S DISEASE
PRESENTED BY
• ADHIYAMAN P M,
M.PHARM. 2nd SEMESTER,
DEPT. OF PHARMACOLOGY,
COLLEGE OF PHARMACY-SRIPMS.
3. INTRODUCTION
• Alzheimer’s disease is the most common form of dementia.
• Progressive disease that destroys memory and other important mental
functions.
• Brain cell connections and the cells themselves degenerate and die.
3
15. Amyloid precursor protein (APP), presenilin (PSEN1) & PSEN2 genes encode APP
metabolism and Aβ generation.
Overexpression of APP causing cellular and molecular alteration.
β-site amyloid precursor protein cleaving enzyme(BACE1) involved in the cleavage
of APP.
siRNA - APP targeted gene therapy
CRISPR-Cas9 suppress Aβ associated pathway
GENE THERAPY
15
16. GENE THERAPY
Apolipoprotein E (APOE) transporter of lipids.
APOE2, APOE3 and APOE4 which carries different risk percentage and differs due
to presence of cysteine(112) or arginine(158) .
APOE4 which increase levels of amyloid while APOE2 has a lower amyloid
burden.
Increase the expression level of APOE2 which prevent Aβ deposition.
16
21. PASSIVE IMMUNIZATION
• Bapineuzumab is an lgG1 antibody that
binds fibrillar and soluble Aβ and activates
microglial phagocytosis and (Phase 3).
21
22. Aβ-TARGETING STRATEGIES
• APP processed by α-secretase within Aβ sequence and generate soluble neurotrophic
sAPPα.
• Accumulation of Aβ in brain leads to oxidative stress, neuronal dysfunction.
• Secondary prevention of AD can be made by:
Decreasing the production of Aβ
Stimulation of clearance of Aβ formed
Prevention of aggregation of Aβ into amyloid plaques
22
23. • Decreasing Aβ neurotoxicity or inhibiting its aggregation have therapeutic
potentials.
• β-sheet breaker iAβ5p, which showed improved spatial memory and decreased
amyloid plaque deposits (Phase 2).
• Upregulation of α-secretase activity which decrease the amount of APP.
• Deprenyl, increase α-secretase activity by promoting ADAM10 and PKC.
Aβ-AGGREGATION INHIBITORS
α-SECRETASE ACTIVATORS/MODULATORS
23
24. β-SECRETASE INHIBITORS
BACE1 inhibitor Lowering of brain Aβ40 and Aβ42.
Decreased APPβ and an increased sAPPα secretion.
KMI-429 reduce Aβ production (Phase 2).
BMS-299897 and MRK560 is a γ-secretase inhibitors (Phase 1 & 3).
γ-secretase modulators, shifting the γ-secretase cutting point to produce shorter,
non-toxic Aβ fragments.
γ-SECRETASE INHIBITORS/MODULATORS
24
25. PREVENTION OF PHOSPHORYLATION OF TAU
Phosphorylation of tau is controlled by different kinases and phosphatases.
The protein phosphatase (PP)-2A increase dephosphorylation of tau.
Cyclin-dependent kinase-5 (CDK5) and Glycogen synthase kinase (GSK)-3β which
phosphorylate tau in AD.
AF267B – inhibit GSK-3β
25
26. CONCLUSION
• Current therapies providing temporary improvement and reducing the rate of
cognitive decline.
• Gene therapy appear is a alternative therapeutics strategy.
• Identifying potential therapeutic compounds.
26
27. BIBLIOGRAPHY
Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer’s disease:
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Marei HE, Althani1 A, Suhonen J, Zowalaty1 ME, Albanna ME, Cenciarelli C, Wang T, Caceci T.
Recent perspective about the amyloid cascade hypothesis and stem cell - based therapy in
the treatment of Alzheimer’s disease. FCDR. 2016; 5: 3-33.
Rang HP, Dale MM, Ritter JM, Flower R, Henderson G. Pharmacology: Neurodegenerative diseases. 9th ed.
Edinburg: Elseveir Ltd; 2020.
Standaert DG, Roberson ED. Treatment of central nervous system degenerative disorders. In: Brunton LL,
Chabner BA, Knollman BC. Goodman & Gilman’s The pharmacological basis of therapeutics. 12th
ed. New York: McGraw - hill medical publishers; 2011.
Thoe ES, Fauzi A, Tang YQ, Chamyuang S, Chia YA. A review on advances of treatment modalities for
Alzheimer’s disease. Life Sci. 2021; 276: 1-15.
Tripathi KD. Essentials of medicinal pharmacology. 8th ed. New delhi: Jaypee medical publishers;
2019. 27