This document summarizes models used to study anti-emetic drugs. It describes various in vivo, in vitro, and human models. For in vivo models, it outlines drug-induced (cisplatin, apomorphine, copper sulfate), motion, and radiation models using species like dogs, cats, ferrets, and rats. It discusses parameters assessed like retching episodes. For in vitro models, it notes evaluating drugs' activity at 5-HT3 receptors. Finally, it mentions human models like using apomorphine or ipecac to induce vomiting and assessing drug effectiveness.
1. The document discusses various models used to study Alzheimer's disease, including both in vitro and in vivo models. It describes assays such as inhibitory avoidance, step-down avoidance, and scopolamine-induced amnesia in mice that are used to test drugs for improving memory and cognition.
2. The pathological hallmarks of Alzheimer's disease involve extracellular amyloid plaques, neurofibrillary tangles, and loss of cortical cholinergic neurons. Several genetic models have also been developed to study the disease.
3. A variety of screening models are used to evaluate potential pharmacological treatments for Alzheimer's disease and assess their ability to inhibit acetylcholinesterase activity, affect nicotinic receptors, or antagonize
This document discusses various in vivo and in vitro models for studying anti-diabetic activity. It describes several chemical, viral, hormonal, and genetic methods for inducing diabetes in rodent models like mice and rats. These include alloxan and streptozotocin to chemically induce diabetes, viruses to infect pancreatic beta cells, growth hormone and corticosteroids to cause hormonal diabetes, and genetic mutations in leptin and leptin receptors. Spontaneous rodent models of obesity-related diabetes like ob/ob, db/db, ZDF, NZO, and OLETF rats are also covered. The document concludes with details of two in vitro assays - amylase inhibition and gl
This document discusses preclinical screening methods for antihypertensive agents using animal models of hypertension. It describes several animal models that mimic different types of human hypertension, including renovascular hypertension induced by clipping the renal artery, dietary hypertension from high salt intake, and genetic hypertension using spontaneous hypertensive rats. The ideal animal model criteria are outlined as well as common methods for measuring blood pressure directly via catheterization or indirectly via tail-cuff. The effects of different classes of antihypertensive drugs are also reviewed.
This document summarizes screening methods for potential antiparkinson agents. It describes several in vivo and in vitro models used to test compounds. The key in vivo models discussed are:
1. Tremorine and oxotremorine antagonism in mice, which tests a compound's ability to reduce tremors induced by these muscarinic agonists.
2. The MPTP model in monkeys and mice, which uses MPTP to damage dopaminergic neurons and induce Parkinson's-like symptoms that can be reversed or reduced by test compounds.
3. Reserpine antagonism in rats, which tests if a compound can reduce sedation and motor impairment caused by reserpine depletion of cate
The document describes several in vitro and in vivo methods used to study anti-allergic and anti-inflammatory drugs. In vitro methods include inhibition of histamine release from mast cells and inhibition of T cell proliferation. In vivo methods include a rat anaphylaxis model, guinea pig Schultz-Dale reaction, and passive cutaneous anaphylaxis in rats. One method involves sensitizing rats with ovalbumin, then challenging them to induce shock, which can be counteracted by test drugs. Another involves sensitizing guinea pigs to egg albumin to study contractions in response to ovalbumin.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
This document summarizes models used to study anti-emetic drugs. It describes various in vivo, in vitro, and human models. For in vivo models, it outlines drug-induced (cisplatin, apomorphine, copper sulfate), motion, and radiation models using species like dogs, cats, ferrets, and rats. It discusses parameters assessed like retching episodes. For in vitro models, it notes evaluating drugs' activity at 5-HT3 receptors. Finally, it mentions human models like using apomorphine or ipecac to induce vomiting and assessing drug effectiveness.
1. The document discusses various models used to study Alzheimer's disease, including both in vitro and in vivo models. It describes assays such as inhibitory avoidance, step-down avoidance, and scopolamine-induced amnesia in mice that are used to test drugs for improving memory and cognition.
2. The pathological hallmarks of Alzheimer's disease involve extracellular amyloid plaques, neurofibrillary tangles, and loss of cortical cholinergic neurons. Several genetic models have also been developed to study the disease.
3. A variety of screening models are used to evaluate potential pharmacological treatments for Alzheimer's disease and assess their ability to inhibit acetylcholinesterase activity, affect nicotinic receptors, or antagonize
This document discusses various in vivo and in vitro models for studying anti-diabetic activity. It describes several chemical, viral, hormonal, and genetic methods for inducing diabetes in rodent models like mice and rats. These include alloxan and streptozotocin to chemically induce diabetes, viruses to infect pancreatic beta cells, growth hormone and corticosteroids to cause hormonal diabetes, and genetic mutations in leptin and leptin receptors. Spontaneous rodent models of obesity-related diabetes like ob/ob, db/db, ZDF, NZO, and OLETF rats are also covered. The document concludes with details of two in vitro assays - amylase inhibition and gl
This document discusses preclinical screening methods for antihypertensive agents using animal models of hypertension. It describes several animal models that mimic different types of human hypertension, including renovascular hypertension induced by clipping the renal artery, dietary hypertension from high salt intake, and genetic hypertension using spontaneous hypertensive rats. The ideal animal model criteria are outlined as well as common methods for measuring blood pressure directly via catheterization or indirectly via tail-cuff. The effects of different classes of antihypertensive drugs are also reviewed.
This document summarizes screening methods for potential antiparkinson agents. It describes several in vivo and in vitro models used to test compounds. The key in vivo models discussed are:
1. Tremorine and oxotremorine antagonism in mice, which tests a compound's ability to reduce tremors induced by these muscarinic agonists.
2. The MPTP model in monkeys and mice, which uses MPTP to damage dopaminergic neurons and induce Parkinson's-like symptoms that can be reversed or reduced by test compounds.
3. Reserpine antagonism in rats, which tests if a compound can reduce sedation and motor impairment caused by reserpine depletion of cate
The document describes several in vitro and in vivo methods used to study anti-allergic and anti-inflammatory drugs. In vitro methods include inhibition of histamine release from mast cells and inhibition of T cell proliferation. In vivo methods include a rat anaphylaxis model, guinea pig Schultz-Dale reaction, and passive cutaneous anaphylaxis in rats. One method involves sensitizing rats with ovalbumin, then challenging them to induce shock, which can be counteracted by test drugs. Another involves sensitizing guinea pigs to egg albumin to study contractions in response to ovalbumin.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
Antipsychotic screening- Dr Divya Krishnan Divya Krishnan
This document summarizes a seminar on screening methods for antipsychotic drugs. It discusses various animal models used to screen antipsychotics, including pharmacological models using dopamine agonists like amphetamine that cause hyperactivity and stereotypy in rats, and glutamatergic models using NMDA antagonists like phencyclidine. Commonly used tests involve measuring a drug's ability to inhibit amphetamine-induced hyperactivity and stereotypy in rats, which can identify drugs with D2 receptor blocking effects. Newer models based on deficits in sensory gating like prepulse inhibition of the startle response are also described. No animal model fully captures the human condition of schizophrenia, but these tests provide methods to screen drugs' antip
This document describes several screening methods used to assess the effects of drugs on motor coordination and muscle function in mice. The methods include the open field test, hole board test, inclined plane test, vertical screen test, rotarod test, and chimney test. Each method is briefly described, including the purpose, apparatus used, procedures, and outcomes measured. The tests evaluate behaviors like locomotion, exploration and curiosity that can be altered by sedative or stimulant drugs.
This document provides an overview of preclinical screening methods used to evaluate potential antipsychotic agents. It first defines psychosis and describes the classification and mechanisms of antipsychotic drugs. It then outlines several in vivo and in vitro models used in preclinical screening, including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and dopamine D2 receptor binding assays. The goal of preclinical screening is to identify new antipsychotic compounds and characterize their efficacy and mechanisms of action before human trials.
Dyslipidemia is a medical condition that refers to an abnormal level of blood lipids.
The most common type of dyslipidemia is hyperlipidemia or high lipid levels.
less common form of dyslipidemia: hypolipidemia, abnormally low lipid levels.
Dyslipidemias can affect any lipid parameters including LDL cholesterol levels, HDL cholesterol levels, triglycerides, or a combination of these lipids.
Two categories:
Primary dyslipidemia
Secondary dyslipidemia
This document describes screening models used to evaluate antihypertensive agents, including both in vitro and in vivo models. It discusses several specific in vitro models like α2-adrenoreceptor binding assays and assays measuring inhibition of angiotensin converting enzyme. It also lists various in vivo models used in rats and dogs to study acute and chronic forms of hypertension. The goal is to screen potential antihypertensive drugs and understand their mechanisms of action through these screening models before testing in clinical trials.
This document discusses various methods used to screen potential anti-arrhythmic drugs, including in vitro and in vivo models. In vitro models include the Langendorff technique using isolated guinea pig hearts. In vivo models include chemically induced arrhythmias using agents like aconitine in rats, electrically induced arrhythmias in dogs, exercise-induced ventricular fibrillation in dogs, and mechanically induced arrhythmias through coronary artery ligation in dogs. These animal models are used to evaluate the effects of test compounds on outcomes like heart rate, contractile force, incidence of arrhythmias, and mortality. While species differences exist, animal studies have helped advance the diagnosis and treatment of arrhythmias in humans.
Multiple sclerosis is a neurodegenerative disorder that affects the central nervous system including the brain, spinal cord, and optic nerves. There are several types of MS defined by their symptoms and progression. The pathophysiology involves the immune system mistakenly attacking the myelin sheath, resulting in plaques/lesions and disrupted nerve signaling. Potential causes include genetic and environmental factors. Several medications are used to treat MS symptoms or reduce immune attack. Screening methods include in vitro tests examining cells involved in MS and in vivo animal models that induce conditions resembling MS through viral infection, toxins, or experimental autoimmune encephalomyelitis.
The document describes several screening models used to evaluate the effects of drugs on behavioral and muscle coordination in animals. It discusses tests such as the open field test, hole board test, chimney test, grip strength, and rota rod method. These tests measure parameters like locomotor activity, exploration, muscle strength, and motor coordination. The results of these tests can provide information about a drug's effects and allow the calculation of values like ED50 doses for sedative, stimulant, and muscle relaxant drugs.
Pharmacological screening of Anti-psychotic agentsAbin Joy
This document provides information on screening models used to evaluate potential antipsychotic drugs. It begins with an introduction to psychosis and classification of antipsychotic agents. It then describes several in vivo and in vitro models used for screening including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and D2 receptor binding assays. The in vivo models assess behaviors relevant to antipsychotic effects while the in vitro assays measure binding to specific receptors like the D2 receptor that contribute to antipsychotic mechanisms of action.
This file includes the general introduction to Alzheimer's, histopathology and Pharmacological treatment of Alzheimer's, preclinical screening models used in Alzheimer's. I hope this file may useful to life science students
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
An assignment in the subject "Pharmacological and Toxicological Screening", 1st year, M.Pharm, Pharmacology, 1st semester. This presentation provides a brief knowledge about Pre-clinical Screening, Hypertension, Its Types, Normal body mechanism in Hypertension, Screening Procedures, Animal models, Animal model criteria, various screening procedures and their evaluation, Recent discovery, Hypertension Facts, Recent Discovery and Treatment for Hypertension.
SCREENING OF DRUGS USED IN ANTIARRYTHMIASreyaRathnaj
This document summarizes information about cardiac arrhythmias. It begins with an introduction defining arrhythmia as a deviation from the heart's normal rhythm. It then discusses normal heart rhythm and the cardiac action potential in detail. It describes several mechanisms that can cause arrhythmias, including enhanced pacemaker activity, after-depolarizations, and reentry. It classifies arrhythmias and lists symptoms. Several in vitro and in vivo models for evaluating antiarrhythmic drugs are presented, including the Langendorff technique, acetylcholine-induced arrhythmias, chemically-induced arrhythmias in rats, digoxin-induced arrhythmias in guinea pigs, and exercise-induced arrhythmias in dogs
This document provides information on screening methods for antidiabetic drugs. It discusses various in vivo and in vitro models used to screen drugs, including chemically-induced diabetes models using alloxan and streptozotocin in animals, genetically diabetic animal models like NOD mice and BB rats, and isolated tissue and cell-based in vitro models. A variety of animal models aim to mimic types 1 and 2 diabetes by destroying pancreatic beta cells or inducing insulin resistance. These preclinical models are used to evaluate new drugs' ability to lower blood glucose levels and treat diabetes symptoms before human trials.
The document discusses various screening methods for evaluating potential anxiolytic drugs, including in vitro receptor binding assays and in vivo behavioral tests in animals like the elevated plus maze test, light-dark box test, and social interaction test, which measure anxiety-like behaviors that can be reduced by anxiolytic drug administration. Classification of anxiolytics and theories of anxiety involving neurotransmitters like GABA, serotonin and norepinephrine are also covered.
screening methods for anti-atherosclerotic agentsPrajitha p
This document summarizes various screening methods for evaluating potential anti-atherosclerotic agents. It discusses methods such as inducing atherosclerosis in animal models like rabbits fed a high-cholesterol diet and evaluating the effects of test compounds. It also covers assays measuring effects on lipid metabolism like inhibiting cholesterol biosynthesis and absorption. Specific assays are described in detail, including the procedures, evaluations, and purposes of evaluating agents' abilities to inhibit enzymes involved in cholesterol synthesis.
This document describes various methods for screening anti-anginal drugs, including both in vivo and in vitro techniques. The isolated heart (Langendorff) preparation is discussed in detail, where a heart is removed and retrogradely perfused to evaluate drug effects on contractility, coronary flow, and other parameters. The isolated heart-lung preparation and coronary artery ligation in isolated rat hearts are also presented as options to study anti-anginal drugs and model ischemia/reperfusion. Various evaluation criteria are provided such as measurements of left ventricular pressure, contractility, coronary flow, and more.
This document summarizes various preclinical screening methods used to evaluate potential anti-epileptic drugs. It describes several animal models of induced seizures including electroshock seizures, chemical-induced seizures using pentylenetetrazol or picrotoxin. It also discusses genetic models like the totterer mouse that is prone to spontaneous seizures. The key methods are maximal electroshock in mice/rats to test generalized tonic-clonic seizure protection and the pentylenetetrazol test in mice to assess anticonvulsant effects against petit mal-like seizures. These preclinical tests aim to predict potential efficacy of new compounds before clinical trials in humans.
Experimental evaluation of anti-diabeticsKirtan Bhatt
This document discusses experimental methods for evaluating anti-diabetic drugs. It describes various animal models of diabetes used, including those induced chemically, genetically, or surgically. Methods for measuring anti-diabetic activity include assessing glucose lowering effects in vivo in animals like rabbits, rats, mice, and dogs. The euglycemic clamp technique, a gold standard method, quantifies insulin sensitivity by infusing glucose to maintain blood sugar levels during insulin infusion in rats. A variety of genetic and transgenic animal models of type 1 and type 2 diabetes are also summarized.
PRECLINICAL SCREENING OF ANTIDIABETICS.pptxVincyDinakaran
DIABETES MELLITUS
Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia, glycosurea, hyperlipidemia, negative nitrogen balance and sometimes ketonaemia resulting from defects in insulin secretion, insulin action or both.
TYPES OF DIABETES MELLITUS
Type 1 : Insulin dependent diabetes mellitus ( IDDM) or Juvenile onset diabetes mellitus
▪︎ beta cell destruction of pancreatic islets
◇type 1A: Autoimmune antibodies that destruct beta cells are present in blood
◇type 1B: idiopathic – no antibodies are detected.
Type 2 :Non insulin dependent diabetes mellitus (NIDDM)or maturity onset diabetes mellitus
CAUSES
Abnormality in gluco-receptor of beta cells
Reduced sensitivity of peripheral tissues to insulin
Excess hyperglycemic hormones (glucagon) or obesity
SCREENING METHODS
IN-VIVO METHODS
A. MODELS FOR IDDM
1. Chemically induced diabetes
a. Alloxan
b. Streptozotocin
2. Hormone induced diabetes
a. Growth hormone
b. Corticosteroid
3. Virus induced diabetes
4. Genetically diabetic models
a. Spontaneously diabetic rats
●BB rat
● WBN/KOB Rat
● Cohen diabetic rat
● Zucker Fatty rat
b. Spontaneously diabetic mouse
● KK mouse
● NOD Mouse
5. Other diabetogenic compounds
a. Dithizone
b. Monosodium glutamate
6. Insulin antibodies
7. Surgically induced diabetes
B MODELS FOR NIDDM ( type 2)
1. Chemically induced diabetes
a. Neonatal STZ Madeleine for NIDDM
2. Genetic models
a. Monogenic model for NIDDM
♧ Yellow mouse (The Agouty Mouse)
♧ Tubby Mouse
♧ Zucker Diabetic Fatty Rat (ZDF)
b. Polygenic model for NIDDM
♧New Zealand Obese Model (NZO)
♧Japanese KK Mouse
c. Transgenic and knock out models
d. Miscellaneous models
♧Invertebrate animal model
♧ Diet induced metabolic dysregulation
IN- VITRO
1. Enzyme Inhibition Assay
a. Alpha amylase inhibition assay
b. Alpha glucosidase inhibition assay
2. Glucose uptake assay
a. Glucose uptake assay yeast cell model
b. Glucose uptake assay by adipocytes cell line
3. Isolated islets from pancreas
4. Cultured skeletal muscle cell
IN- VITRO
1. Enzyme Inhibition Assay
a. Alpha amylase inhibition assay
b. Alpha glucosidase inhibition assay
2. Glucose uptake assay
a. Glucose uptake assay yeast cell model
b. Glucose uptake assay by adipocytes cell line
3. Isolated islets from pancreas
4. Cultured skeletal muscle cell
In-vivo methods
1. ALLOXAN INDUCED DIABETES
Alloxan is a cyclic analogue , reported to produce reversible diabetes in animals.
Widely used to produce diabetes in rats, mice, rabbits and dogs.
Selective uptake of the compound due to its structural similarity to glucose and highly efficient uptake mechanism of pancreatic beta cells.
Antipsychotic screening- Dr Divya Krishnan Divya Krishnan
This document summarizes a seminar on screening methods for antipsychotic drugs. It discusses various animal models used to screen antipsychotics, including pharmacological models using dopamine agonists like amphetamine that cause hyperactivity and stereotypy in rats, and glutamatergic models using NMDA antagonists like phencyclidine. Commonly used tests involve measuring a drug's ability to inhibit amphetamine-induced hyperactivity and stereotypy in rats, which can identify drugs with D2 receptor blocking effects. Newer models based on deficits in sensory gating like prepulse inhibition of the startle response are also described. No animal model fully captures the human condition of schizophrenia, but these tests provide methods to screen drugs' antip
This document describes several screening methods used to assess the effects of drugs on motor coordination and muscle function in mice. The methods include the open field test, hole board test, inclined plane test, vertical screen test, rotarod test, and chimney test. Each method is briefly described, including the purpose, apparatus used, procedures, and outcomes measured. The tests evaluate behaviors like locomotion, exploration and curiosity that can be altered by sedative or stimulant drugs.
This document provides an overview of preclinical screening methods used to evaluate potential antipsychotic agents. It first defines psychosis and describes the classification and mechanisms of antipsychotic drugs. It then outlines several in vivo and in vitro models used in preclinical screening, including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and dopamine D2 receptor binding assays. The goal of preclinical screening is to identify new antipsychotic compounds and characterize their efficacy and mechanisms of action before human trials.
Dyslipidemia is a medical condition that refers to an abnormal level of blood lipids.
The most common type of dyslipidemia is hyperlipidemia or high lipid levels.
less common form of dyslipidemia: hypolipidemia, abnormally low lipid levels.
Dyslipidemias can affect any lipid parameters including LDL cholesterol levels, HDL cholesterol levels, triglycerides, or a combination of these lipids.
Two categories:
Primary dyslipidemia
Secondary dyslipidemia
This document describes screening models used to evaluate antihypertensive agents, including both in vitro and in vivo models. It discusses several specific in vitro models like α2-adrenoreceptor binding assays and assays measuring inhibition of angiotensin converting enzyme. It also lists various in vivo models used in rats and dogs to study acute and chronic forms of hypertension. The goal is to screen potential antihypertensive drugs and understand their mechanisms of action through these screening models before testing in clinical trials.
This document discusses various methods used to screen potential anti-arrhythmic drugs, including in vitro and in vivo models. In vitro models include the Langendorff technique using isolated guinea pig hearts. In vivo models include chemically induced arrhythmias using agents like aconitine in rats, electrically induced arrhythmias in dogs, exercise-induced ventricular fibrillation in dogs, and mechanically induced arrhythmias through coronary artery ligation in dogs. These animal models are used to evaluate the effects of test compounds on outcomes like heart rate, contractile force, incidence of arrhythmias, and mortality. While species differences exist, animal studies have helped advance the diagnosis and treatment of arrhythmias in humans.
Multiple sclerosis is a neurodegenerative disorder that affects the central nervous system including the brain, spinal cord, and optic nerves. There are several types of MS defined by their symptoms and progression. The pathophysiology involves the immune system mistakenly attacking the myelin sheath, resulting in plaques/lesions and disrupted nerve signaling. Potential causes include genetic and environmental factors. Several medications are used to treat MS symptoms or reduce immune attack. Screening methods include in vitro tests examining cells involved in MS and in vivo animal models that induce conditions resembling MS through viral infection, toxins, or experimental autoimmune encephalomyelitis.
The document describes several screening models used to evaluate the effects of drugs on behavioral and muscle coordination in animals. It discusses tests such as the open field test, hole board test, chimney test, grip strength, and rota rod method. These tests measure parameters like locomotor activity, exploration, muscle strength, and motor coordination. The results of these tests can provide information about a drug's effects and allow the calculation of values like ED50 doses for sedative, stimulant, and muscle relaxant drugs.
Pharmacological screening of Anti-psychotic agentsAbin Joy
This document provides information on screening models used to evaluate potential antipsychotic drugs. It begins with an introduction to psychosis and classification of antipsychotic agents. It then describes several in vivo and in vitro models used for screening including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and D2 receptor binding assays. The in vivo models assess behaviors relevant to antipsychotic effects while the in vitro assays measure binding to specific receptors like the D2 receptor that contribute to antipsychotic mechanisms of action.
This file includes the general introduction to Alzheimer's, histopathology and Pharmacological treatment of Alzheimer's, preclinical screening models used in Alzheimer's. I hope this file may useful to life science students
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
An assignment in the subject "Pharmacological and Toxicological Screening", 1st year, M.Pharm, Pharmacology, 1st semester. This presentation provides a brief knowledge about Pre-clinical Screening, Hypertension, Its Types, Normal body mechanism in Hypertension, Screening Procedures, Animal models, Animal model criteria, various screening procedures and their evaluation, Recent discovery, Hypertension Facts, Recent Discovery and Treatment for Hypertension.
SCREENING OF DRUGS USED IN ANTIARRYTHMIASreyaRathnaj
This document summarizes information about cardiac arrhythmias. It begins with an introduction defining arrhythmia as a deviation from the heart's normal rhythm. It then discusses normal heart rhythm and the cardiac action potential in detail. It describes several mechanisms that can cause arrhythmias, including enhanced pacemaker activity, after-depolarizations, and reentry. It classifies arrhythmias and lists symptoms. Several in vitro and in vivo models for evaluating antiarrhythmic drugs are presented, including the Langendorff technique, acetylcholine-induced arrhythmias, chemically-induced arrhythmias in rats, digoxin-induced arrhythmias in guinea pigs, and exercise-induced arrhythmias in dogs
This document provides information on screening methods for antidiabetic drugs. It discusses various in vivo and in vitro models used to screen drugs, including chemically-induced diabetes models using alloxan and streptozotocin in animals, genetically diabetic animal models like NOD mice and BB rats, and isolated tissue and cell-based in vitro models. A variety of animal models aim to mimic types 1 and 2 diabetes by destroying pancreatic beta cells or inducing insulin resistance. These preclinical models are used to evaluate new drugs' ability to lower blood glucose levels and treat diabetes symptoms before human trials.
The document discusses various screening methods for evaluating potential anxiolytic drugs, including in vitro receptor binding assays and in vivo behavioral tests in animals like the elevated plus maze test, light-dark box test, and social interaction test, which measure anxiety-like behaviors that can be reduced by anxiolytic drug administration. Classification of anxiolytics and theories of anxiety involving neurotransmitters like GABA, serotonin and norepinephrine are also covered.
screening methods for anti-atherosclerotic agentsPrajitha p
This document summarizes various screening methods for evaluating potential anti-atherosclerotic agents. It discusses methods such as inducing atherosclerosis in animal models like rabbits fed a high-cholesterol diet and evaluating the effects of test compounds. It also covers assays measuring effects on lipid metabolism like inhibiting cholesterol biosynthesis and absorption. Specific assays are described in detail, including the procedures, evaluations, and purposes of evaluating agents' abilities to inhibit enzymes involved in cholesterol synthesis.
This document describes various methods for screening anti-anginal drugs, including both in vivo and in vitro techniques. The isolated heart (Langendorff) preparation is discussed in detail, where a heart is removed and retrogradely perfused to evaluate drug effects on contractility, coronary flow, and other parameters. The isolated heart-lung preparation and coronary artery ligation in isolated rat hearts are also presented as options to study anti-anginal drugs and model ischemia/reperfusion. Various evaluation criteria are provided such as measurements of left ventricular pressure, contractility, coronary flow, and more.
This document summarizes various preclinical screening methods used to evaluate potential anti-epileptic drugs. It describes several animal models of induced seizures including electroshock seizures, chemical-induced seizures using pentylenetetrazol or picrotoxin. It also discusses genetic models like the totterer mouse that is prone to spontaneous seizures. The key methods are maximal electroshock in mice/rats to test generalized tonic-clonic seizure protection and the pentylenetetrazol test in mice to assess anticonvulsant effects against petit mal-like seizures. These preclinical tests aim to predict potential efficacy of new compounds before clinical trials in humans.
Experimental evaluation of anti-diabeticsKirtan Bhatt
This document discusses experimental methods for evaluating anti-diabetic drugs. It describes various animal models of diabetes used, including those induced chemically, genetically, or surgically. Methods for measuring anti-diabetic activity include assessing glucose lowering effects in vivo in animals like rabbits, rats, mice, and dogs. The euglycemic clamp technique, a gold standard method, quantifies insulin sensitivity by infusing glucose to maintain blood sugar levels during insulin infusion in rats. A variety of genetic and transgenic animal models of type 1 and type 2 diabetes are also summarized.
PRECLINICAL SCREENING OF ANTIDIABETICS.pptxVincyDinakaran
DIABETES MELLITUS
Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia, glycosurea, hyperlipidemia, negative nitrogen balance and sometimes ketonaemia resulting from defects in insulin secretion, insulin action or both.
TYPES OF DIABETES MELLITUS
Type 1 : Insulin dependent diabetes mellitus ( IDDM) or Juvenile onset diabetes mellitus
▪︎ beta cell destruction of pancreatic islets
◇type 1A: Autoimmune antibodies that destruct beta cells are present in blood
◇type 1B: idiopathic – no antibodies are detected.
Type 2 :Non insulin dependent diabetes mellitus (NIDDM)or maturity onset diabetes mellitus
CAUSES
Abnormality in gluco-receptor of beta cells
Reduced sensitivity of peripheral tissues to insulin
Excess hyperglycemic hormones (glucagon) or obesity
SCREENING METHODS
IN-VIVO METHODS
A. MODELS FOR IDDM
1. Chemically induced diabetes
a. Alloxan
b. Streptozotocin
2. Hormone induced diabetes
a. Growth hormone
b. Corticosteroid
3. Virus induced diabetes
4. Genetically diabetic models
a. Spontaneously diabetic rats
●BB rat
● WBN/KOB Rat
● Cohen diabetic rat
● Zucker Fatty rat
b. Spontaneously diabetic mouse
● KK mouse
● NOD Mouse
5. Other diabetogenic compounds
a. Dithizone
b. Monosodium glutamate
6. Insulin antibodies
7. Surgically induced diabetes
B MODELS FOR NIDDM ( type 2)
1. Chemically induced diabetes
a. Neonatal STZ Madeleine for NIDDM
2. Genetic models
a. Monogenic model for NIDDM
♧ Yellow mouse (The Agouty Mouse)
♧ Tubby Mouse
♧ Zucker Diabetic Fatty Rat (ZDF)
b. Polygenic model for NIDDM
♧New Zealand Obese Model (NZO)
♧Japanese KK Mouse
c. Transgenic and knock out models
d. Miscellaneous models
♧Invertebrate animal model
♧ Diet induced metabolic dysregulation
IN- VITRO
1. Enzyme Inhibition Assay
a. Alpha amylase inhibition assay
b. Alpha glucosidase inhibition assay
2. Glucose uptake assay
a. Glucose uptake assay yeast cell model
b. Glucose uptake assay by adipocytes cell line
3. Isolated islets from pancreas
4. Cultured skeletal muscle cell
IN- VITRO
1. Enzyme Inhibition Assay
a. Alpha amylase inhibition assay
b. Alpha glucosidase inhibition assay
2. Glucose uptake assay
a. Glucose uptake assay yeast cell model
b. Glucose uptake assay by adipocytes cell line
3. Isolated islets from pancreas
4. Cultured skeletal muscle cell
In-vivo methods
1. ALLOXAN INDUCED DIABETES
Alloxan is a cyclic analogue , reported to produce reversible diabetes in animals.
Widely used to produce diabetes in rats, mice, rabbits and dogs.
Selective uptake of the compound due to its structural similarity to glucose and highly efficient uptake mechanism of pancreatic beta cells.
This document discusses diabetes, including its types, prevalence, and screening of anti-diabetic drugs. It outlines models for type 1 diabetes, including chemically-induced and virus-induced models. Models for type 2 diabetes are also described, such as chemically-induced, surgery-induced, and spontaneous diabetic animal models. Specific models discussed in detail include alloxan-induced diabetes, streptozotocin-induced diabetes, insulin deficiency due to insulin antibodies, encephalomyocarditis virus-induced diabetes, total pancreatectomy, neonatal streptozotocin-induced diabetic rats, and NAD and streptozotocin-induced diabetic animals.
This document discusses various methods for evaluating antidiabetic drugs, including both experimental and clinical methods. Experimentally, several animal models are used to induce either type 1 or type 2 diabetes for testing potential antidiabetic drugs. For type 1 diabetes, models include alloxan-induced, streptozotocin-induced, hormone-induced, virus-induced, and spontaneous models. For type 2 diabetes, models include streptozotocin-induced in neonates, spontaneous models, and diazoxide-induced models. The document then describes various animal species and strains used as models, as well as methods for each model of inducing diabetes. Clinical evaluation of antidiabetic drugs involves phase I-IV trials
The document discusses various in vivo and in vitro models used to study diabetes and evaluate potential antidiabetic drugs. It describes methods like streptozocin-induced diabetes in rats to study effects on blood glucose levels and cataract formation. Insulin antibody-induced diabetes in guinea pigs is also presented. In vivo blood glucose lowering effects are evaluated in rabbits/mice following oral administration of test compounds. In vitro assays include testing effects on insulin secretion using isolated organs and cells as well as insulin receptor binding assays.
Screening Models for Anti-Diabetic Drugs.Nisar Ali
in this slide, You will get to know about different screening Invivo and Invitro models used for screening of Anti-Diabetic drugs used in Pharmacology.
The document discusses screening methods and goals for managing diabetes. It describes laboratory blood glucose tests such as the glucose oxidase method and use of glucometers to test blood sugar levels. The HbA1c test measures average blood sugar over the past 3 months. The document also lists the top 10 countries for diabetes prevalence and risk factors, types, and complications of the disease.
ANIMAL MODELS FOR BIOLOGICAL SCREENING OF ANTI-DIABETIC DRUGSGOPALASATHEESKUMAR K
This document discusses various animal models used for type 1 and type 2 diabetes research. It begins by describing chemically-induced models using streptozotocin and alloxan to damage pancreatic beta cells in rats and mice. It also discusses genetically-induced models such as neonatal streptozotocin rats and goldthioglucose obese diabetic mice. Finally, it briefly mentions surgically-induced models involving partial or full pancreatectomy in animals. The document provides details on how to induce diabetes in these various animal models and evaluates their relevance for studying type 1 and type 2 diabetes.
This document discusses various in vivo and in vitro screening models for evaluating potential antidiabetic drugs. It describes four major types of diabetes and their symptoms. For in vivo models, it covers chemically-induced diabetes models using alloxan and streptozotocin, hormonally-induced models, virus-induced models, and genetically derived diabetic animal models. For in vitro models, it discusses methods to study the effects of drugs on the liver, muscles, pancreas, and adipose tissue by using isolated cells and tissues. Complications of diabetes include damage to blood vessels, eyes, nerves and kidneys if blood sugar levels remain poorly controlled over time.
screening methodes of anti-diabetic drugsborude123
Diabetes mellitus is chronic metabolic disease , occurs when the pancreas is not producing insulin or produced insulin cannot be used by the body, or combination of both.
Models for screening of antidiabetic agentsTabindah Hesam
This document discusses various animal models used for screening antidiabetic drugs. It describes models for both type 1 diabetes mellitus (IDDM) and type 2 diabetes mellitus (NIDDM). For IDDM, it discusses chemically-induced models using alloxan and streptozotocin, antibody-induced models, virus-induced models, surgically-induced models, and genetic models like non-obese diabetic mice. For NIDDM it discusses chemically-induced, hormone-induced, and genetic polygenic and monogenic models like Zucker diabetic fatty rats and db/db mice. It provides details on how each model is used to mimic different aspects of human diabetes.
Determination of Blood Glucose Using Glusose Oxidase-Peroxidase MethodZoldylck
This document discusses blood glucose determination using the oxidase-peroxidase method. It begins by introducing diabetes and its prevalence worldwide. It then describes the materials and methodology used, which involves collecting a blood sample, separating the plasma, and adding an O-toluidine reagent before measuring absorbance. The results showed the patient's glucose level was within the normal range. It further discusses hyperglycemia and hypoglycemia, the different types of diabetes, diagnostic criteria, and gestational diabetes.
This document discusses diabetes mellitus, including:
- It is a disease where the body does not properly produce or use insulin, leading to high blood glucose levels.
- There are two main types - type 1 caused by lack of insulin production and type 2 caused by insulin resistance.
- Clinical signs include increased urination, thirst, weight loss, and cataracts in dogs. Diagnosis involves testing blood glucose and fructosamine levels. Treatment focuses on achieving normal blood sugar through insulin, diet, exercise and medication. Medical nutrition therapy and exercise are important parts of long-term diabetes management.
This document discusses various types of diabetes and animal models used to study diabetes. It describes the main types of diabetes as type 1, type 2, and gestational diabetes. It then provides details on several methods for inducing diabetes in animal models, including chemically induced models using alloxan and streptozotocin, genetically induced models using various diabetic rat and mouse strains, and other models such as viral infection, hormone manipulation, and antibody induction. Specific protocols are outlined for commonly used chemical diabetes induction methods and some genetically induced rodent strains.
Introduction to Diabetes & anti diabetic drug screening methodsAnurag Raghuvanshi
This document provides an introduction to diabetes and anti-diabetic drug screening methods. It begins by classifying diabetes and defining the main types - type 1, type 2, gestational, and secondary. It then describes the pancreas and its beta cells that produce insulin. Various models for inducing diabetes in animals are discussed for screening anti-diabetic drugs, including chemical agents like alloxan and streptozotocin, viral induction, immune-mediated induction using anti-insulin serum, genetic alteration in mice/rats, pancreatectomy, and hormone-induced using dexamethasone. Common screening methods and their principles, procedures, advantages, and limitations are summarized.
Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar levels resulting from defects in insulin secretion or action. There are three main types of diabetes: type 1 diabetes where the body does not produce insulin; type 2 diabetes where the body does not produce enough insulin or cells do not respond properly to insulin; and gestational diabetes which develops during pregnancy. Risk factors include heredity, obesity, age, and unhealthy lifestyle habits. Symptoms include increased thirst, hunger, urination, fatigue, and weight loss. Treatment involves diet, exercise, medication including insulin injections, and blood sugar monitoring. Complications can affect the kidneys, nerves, eyes, and heart if not properly managed.
The document discusses diabetes and related topics. It defines diabetes, describes the different types, and explains insulin and its role in regulating blood glucose levels. It provides recommendations from WHO on diagnosing hyperglycemia in pregnancy. It lists plant families and compounds that show antidiabetic properties. Herbal drugs are classified based on their mechanisms of action and secondary metabolites. Various antidiabetic herbs, parts used, and active components are outlined. Symptoms and classes of oral hypoglycemic drugs are also mentioned.
Screening methods for antidiabetic agentsayanarkumar19
This document describes various in vitro and in vivo screening methods for evaluating potential antidiabetic agents. In vitro methods include testing compounds using isolated pancreatic tissue from rats, isolated hepatocytes, and muscle cell lines to assess effects on insulin secretion and glucose uptake. In vivo methods involve inducing diabetes in animal models through chemicals like alloxan and streptozotocin or using hormones and viruses. Potential antidiabetic compounds are then administered and blood glucose levels are measured to evaluate if the compound can lower blood sugar.
This document discusses diabetes mellitus in dogs and cats. It defines diabetes as a chronic disorder of carbohydrate metabolism caused by relative or absolute insulin deficiency. The two main types of diabetes are type 1, caused by immune-mediated destruction of pancreatic beta cells, and type 2, caused by insulin resistance and impaired insulin secretion. Clinical signs in dogs include polydipsia, polyuria, polyphagia, weight loss, and ketotic breath. Management involves insulin therapy, dietary management, weight control, and possibly oral hypoglycemic medications.
Similar to Methods for screening of hypoglycemics (20)
- The document summarizes a preclinical study that evaluated the acute and sub-acute oral toxicity of a multi-targeted polyherbal formulation intended for obesity management.
- In an acute oral toxicity test in rats, no mortality was observed at a dose of 2000mg/kg, establishing the LD50 as greater than 2000mg/kg. Body weight decreased gradually but no clinical signs were observed.
- A 28-day sub-acute oral toxicity study in rats revealed no abnormal signs at doses up to 1000mg/kg but mortality at higher doses of 300mg/kg and 1000mg/kg. Some changes were seen in hematological and biochemical parameters.
- The study concluded the polyherbal formulation is
This document discusses various types of fungi that can cause infections and the antifungal drugs used to treat them. It notes that fungi have more complex cell structures than bacteria. Common fungal infections mentioned include candidiasis, which can occur in the mouth, vagina, and other areas. The main classes of antifungal drugs covered are azoles, polyenes, allylamines, echinocandins, and antimetabolites. Their mechanisms of action target components of fungal cell membranes like ergosterol to disrupt function. Specific drugs discussed are amphotericin B, nystatin, griseofulvin, flucytosine, fluconazole, terbinaf
Subacute toxicity testing is conducted over 28 days to estimate safety margins of substances. It involves exposing test animals like rats to substances via oral, dermal or inhalation routes and observing for signs of toxicity. Key guidelines for subacute toxicity testing are OECD 407 for oral exposure, OECD 410 for dermal exposure, and OECD 412 for inhalation exposure. These studies provide important toxicity data used in chemical risk assessments.
1. Acute toxicity studies evaluate the toxic effects of substances administered in single or multiple doses over a short period, typically up to 14 days. They determine lethal doses and are used for hazard classification.
2. Subacute and chronic toxicity studies evaluate effects from repeated exposure over longer periods, from 1-3 weeks or 12 months respectively. They assess effects on organ systems and determine no observed effect levels.
3. Key differences in oral, dermal and inhalation chronic toxicity studies include the route of exposure (oral daily, dermal 6 hours/day for skin, inhalation 6 hours/day) and duration of at least 12 months.
Antiviral drugs work by targeting specific parts of the viral replication cycle using mechanisms like inhibiting viral enzymes or incorporating into viral DNA to stop replication. They are classified based on the virus or viral enzyme they target, such as anti-herpes drugs like acyclovir that inhibit viral DNA polymerase, or anti-HIV drugs that include reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors. Developing effective antiviral drugs is challenging because viruses replicate inside cells and mutate rapidly, so they must target virus-specific processes without harming host cells.
Tuberculosis is caused by Mycobacterium tuberculosis and remains a major health problem in India with over 2 million cases annually. It is treated using a combination of anti-tubercular drugs to prevent resistance. First line drugs include isoniazid, rifampicin, pyrazinamide, and ethambutol. These are given in an initial intensive phase and then a continuation phase to fully treat the infection. Second line drugs are used when resistance develops or for intolerances. New drugs are also being developed and tested in clinical trials to improve treatment outcomes.
The document discusses various routes of drug administration in laboratory animals. It describes enteral routes including oral, intragastric gavage, and rectal administration. It also discusses various parenteral routes such as intravenous, intramuscular, subcutaneous, intraperitoneal, and intradermal injection. For each route, it provides details on the procedure, optimal injection sites and volumes for rats and mice. Common laboratory animals used include rats, mice, rabbits, guinea pigs, cats, dogs and monkeys.
Para-sympathomimetics can directly activate cholinergic receptors as agonists or indirectly increase acetylcholine levels by inhibiting acetylcholinesterase. Direct agonists include natural alkaloids like muscarine and synthetic ones like carbachol. Indirect anticholinesterases prevent acetylcholine degradation, either reversibly like neostigmine or irreversibly like organophosphates. Their effects are mediated through muscarinic and nicotinic receptors in the autonomic ganglia, neuromuscular junction and central nervous system. They have therapeutic uses for conditions like glaucoma and myasthenia gravis but overdose can cause toxic effects that require atropine and oxime
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...Donc Test
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Study Guide Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Course Hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Answers Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Course hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Study Guide Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Ebook Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Questions Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Stuvia
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
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.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
2. •Diabetes is a chronic metabolic disorder characterized
by either the insufficient production or the lack of
response to a key regulatory hormone of the body’s
metabolism, insulin.
•It can be categorized as Type-1 diabetes [insulin
dependent diabetes mellitus (IDDM)] and Type-2
diabetes [non- insulin dependent diabetes mellitus
(NIDDM)].
•The overall prevalence of diabetes is approximately 10%
of the population, of which 90% is Type-2.
3. •The disease is characterized by hyperglycemia,
hypercholesterolemia, and hypertriglyceridemia,
resulting from defects in insulin secretion or
reduced sensitivity of the tissue to insulin (insulin
resistance) and/or combination of both.
•Characteristically, it is a serious endocrine
syndrome with poor metabolic control and
responsible for increased risk of cardiovascular
diseases including atherosclerosis, renal failure,
blindness or diabetic cataract.
4.
5.
6. Types of Diabetes
TYPE-1 (IDDM)/Juvenile Onset
Diabetes Mellitus
There is β –Cell destruction in
pancreatic islets.
It is an autoimmune disease.
It is very rare.
Risk factors: Age (Children)
Family History
Incidence is growing Steadily.
Treatment: By Injecting Insulin
into body.
TYPE-2 (NIDDM)/Maturity Onset
Diabetes Mellitus
There is no loss or moderate
reduction in β-cell mass.
It usually begins as insulin
resistance.
It is very common.
Risk Factors: Obesity, Age above 45
Incidence is rising at an epidemic
rate
Treatment: With diet and exercise,
Monitoring blood sugar level,
Medications.
7. Current treatment modalities
•Different insulin preparations and different
insulin delivery systems
• Sulfonylureas
• Biguanides
• Meglitinides
• Thiazolidinediones
• α- glucosidase inhibitors
8. Screening helps us to understand
PATHOGENESIS
SAFETY AND EFFICACY OF
DRUGS
PREVENTION
OF DISEASE COMPLICATIONS
THERAPEUTIC
AGENTS
9. Methods for screening of Hypoglycemics
1- Methods to Induce Experimental Diabetes
Mellitus.
A. Pancreatectomyin Dogs.
B. Alloxan - Induced Diabetes.
C. Streptozotocin – Induced Diabetes .
D.Growth Hormone-Induced Diabetes.
E. Insulin Deficiency Due to Insulin Antibodies.
10. 2- Genetically Diabetic Animals
A. Spontaneously Diabetic Rats.
B. Spontaneously Diabetic Mice.
C. Chinese Hamster.
D.Transgenic Animals and Knockout Mice .
E. Metabolic Systems Biology
11. 3 - Measurement of Blood Glucose-Lowering
and Antidiabetic Activity
A.Blood Glucose-Lowering Effect in Rats.
B. Blood Glucose-Lowering Effect in Mice.
C. Euglycemic Clamp Technique.
D.Effects of Insulin Sensitizer Drugs.
E. Effects of Thiazolidinediones on Peroxisome
Proliferator Activated Receptor-γ.
12. 4-Measurement of Insulin and Other Glucose-
Regulating Peptide Hormones.
A. Radio immunoassays for Insulin, Glucagon and
Somatostatin
B. Amylin
C. Receptor Binding and In Vitro Activity of Glucagon
D. Glucagon-Like Peptide I
E. Insulin-Like Growth Factors.
13. 5-Insulin Target Tissues and Cells
A. Adipose Tissue and Adipocytes.
a. Epididymal Fat Pads of Rats.
b. Primary Rat Adipocytes.
c. Insulin-Resistant Primary Rat Adipocytes.
d. Primary Rat Hepatocytes .
14. 6-Assays for Insulin and Insulin Like Metabolic
activity
a) Assays for Insulin and Insulin-Like Activity Based on Adipocytes
b) Assays for Insulin and Insulin Like Metabolic Activity Based on
Hepatocytes, Myocytes and Diaphragms
c) Assays for Insulin and Insulin-Like Signal Transduction Based on
Adipocytes, Hepatocytes and Myocytes
d) Assays for Insulin and Insulin-Like Regulation of Gene and Protein
Expression
e) Assays for Insulin and Insulin-Like Regulation of Energy Metabolism.
15. 7-Measurement of Glucose Absorption
A.Inhibition of Polysaccharide Degrading
Enzymes
eg - Assay for α-Amylase
B. Assays for GLUT2 Transport Activity
eg - Perfusion of Jejunal Loops
C. Evaluation of Glucose Absorption In Vivo
16. 8- Monitoring of Diabetic Late
Complications
A. Aldose Reductase Activity.
B. Nerve Conduction Velocity.
C. Nerve Blood Flow (Doppler Flux)
D. Electroretinogram.
E. Streptozotocin-Induced Cataract.
17. 9- Insulin Analogs: Assessment of
Insulin Mitogenicity and IGF-I Activity.
A. Introduction and Application to Insulin
Analogs
B. Signaling Via Insulin Receptor
C. IGF-I Receptor Affinity.
D. Insulin Receptor Affinity
E. Assessment of Hypoglycemic Activity In Vivo.
18. 1. Methods to Induce Experimental
Diabetes Mellitus
A - Alloxan induced Diabetes
•Alloxan is a cyclic urea (tetra- oxo – hexa hydro
pyrimidine)
Purpose : Alloxan has direct cytotoxic action on beta
cells of pancreas. It selectively destroy beta cells and
produce insulin deficiency and hyperglycemia.
19. Mechanism of action
-Free radical damage beta cell DNA
- Reacts with protein SH group causing cell necrosis
Procedure
• Rats - Sprague Dawley (SD) strain weighing 150-200
gms
Alloxan standard solution is prepared at a strength
of 5gm/100ml kept at pH 4.5
20. Alloxan is injected by :
-Intravenous - 65mg/kg
- Subcutaneous 100–175 mg/ kg
- Intraperitoneal 100–175 mg/ kg
•Triphasic response:
- at 2hr, hyperglycemia
- at 8hr, hypoglycemia
- at 24 hr, hyperglycemia
21. Drawbacks
•Risk of high mortality (up to 50%)
• Unstable at physiological pH, so care is taken to see
that it is preserved at a pH of 4.5.
•Dosage variation with age & species.
•This process has been almost completely replaced by
streptozotocin for inducing diabetes because of
these drawbacks.
22. B -Streptozotocin induced diabetes
PURPOSE
AND
RATIONALE
Rakieten and coworkers (1963) reported
the diabetogenic activity of the antibiotic
streptozotocin. The compound turned out
to be specifically cytotoxic to beta-cells of
the pancreas.
24. Three phases of changed blood glucose level are observed.
Initially after 3hrs glucose level increased upto 150- 200mg/dl.
After 8hrs, serum insulin values are increased upto 4 times
Male Wistar rats weighing 150–220g fed
with a standard diet, are injected with
60mg/kg streptozotocin prepared in
citrated buffer.(4.5pH)
Procedure
25. After 24- 28 hrs hyperglycemia already occur reaching values
800mg/dl with glycosuria & ketonemia. Histologically beta
cells are degranulated.
After 14 days animal is used for pharmacological effect
Hypoglycemic phase followed by hyperglycemia
27. Advantages
Almost replaced Alloxan because of
greater selectivity towards β cells
Lower mortality rate
Longer duration diabetes induction
28. Disadvantages
Highly unstable at room temperature
(preserved at 20 0C)
Single dose may not give results
therefore streptozotocin might also be
given 2 divided doses 4 hrs apart
Necessary to maintain cold
temperature
29. Some modifications with STZ
• Multiple low doses of STZ induce immune
mediated insulitis mimicking type 1 DM.
• Enhancement of streptozotocin induced
diabetes in CD-1 mice by cyclosporin A.
• Streptozotocin combined with complete
Freund’s adjuvant, incomplete freund’s adjuvant,
Mycobacterium butyricum,Listeria
monocytogenes, or endotoxin all produce
hyperglycemia.
30. 2-Genetically Diabetic Animals
A - Transgenic Animals and Knockout Mice
Purpose and
rationale :
The genes controlling various aspects of metabolism and insulin
secretion are manipulated to produce animal models of diabetes
mellitus.
Transgenic animals are animals (most commonly mice) that have had a
foreign gene deliberately inserted into their genome.
31. There is an another method which is commonly used
to manipulate a single gene, in most cases and this
involves removing or 'knocking out' a target gene..
The end result is what is known as a ‘knockout’
animal.
This results in the genetically modified offspring
The progeny are then bred with other transgenic
offspring to establish a transgenic line.
32. The genes are manipulated :
To cause insulin resistance
insulin receptor
insulin receptor substrate 1 & 2
Glucose transporters
Hexokinase ІІ
Tumor necrosis factor- α
Fatty acid-binding protein
RAS associated with diabetes
33. To cause defective insulin secretion
GLUT-2 (trans membrane carrier protein that
enables protein facilitated glucose movement
across the cell membrane)
Glucokinase
Hepatic nuclear factors
Islet amyloid polypeptide
Or genes that increase body fat
Knock out of uncoupling proteins
Knock out of β3-adrenergic factors
34. 3 - Measurement of Blood Glucose-Lowering and
Antidiabetic Activity
A – Blood Glucose-Lowering Effect in Rats
PURPOSE
AND
RATIONALE
Rats are used for screening as well as for
quantitative evaluation of blood glucose
lowering agents.
35. Male Wistar rats weighing 180 – 240g are kept on standard diet
Procedure
Groups of 4–7 non-fasted animals are treated orally or intraperitoneally
with various doses of the test compounds suspended in 0.4% starch
suspension
One control group receives the vehicle only
36. Blood is withdrawn from the tip of the tail immediately before, and 1, 2, 3,
5, and 24h after administration of the test compound.
Blood glucose is determined in 10µl blood samples with the hexokinase
enzyme method (Gluco quant test kit).
37. EVALUATION
•Average blood sugar values are plotted versus time
for each dosage.
•Besides the original values, percentage data related
to the value before the experiment are calculated.
•Mean effects over a time period are calculated
using the trapezoidal rule.
•Statistical evaluation is performed as:
38. •The values of the experimental group are compared
statistically with the t-test for each time interval with
those of the control group.
• Differences between several treated groups and the
control group are tested using a simultaneous
comparison.
39. B - In vivo-Euglycemic clamp technique
• Useful method of quantifying in vivo insulin
sensitivity in male wistar rats
•In this technique, a variable glucose infusion is
delivered to maintain euglycemia during insulin
infusion
•Whole-body tissue sensitivity to insulin, as
determined by net glucose uptake, can be
quantitated under conditions of near steady state
glucose & insulin levels
40. Male Wistar rats weighing 150–200g are fasted overnight and
anesthetized with pentobarbital (40mg/ kg, i.p.).
Catheters are inserted into a jugular vein and a femoral vein for blood
collections and insulin and glucose infusion, respectively.
To evaluate the insulin action under physiological hyperinsulinemia (steady
state plasma insulin concentration during the clamp test around
100µU/dl),and maximal hyperinsulinemia (under which maximal insulin
action may appear) two insulin infusion rates, 6 and 30mU/kg/min, are used.
The blood glucose concentrations are determined from
samples collected at 5-min intervals during the 90-min clamp
test.
41. The glucose infusion rate is adjusted so as to maintain the blood
glucose at its basal level during the clamp test.
The final glucose infusion rate is calculated from the amount of
glucose infused for the last 30min (from 60 to 90min after start of
the clamp) in which the blood glucose levels are in a steady state.
The glucose metabolic clearance rate is obtained by dividing the
glucose infusion rate by the steady state blood glucose
concentration.
The steady state plasma insulin concentration is calculated from the
insulin concentrations at 60and 90min after the start of the clamp.
At the start and end of the euglycemic clamp test, free fatty acid
concentration is also determined and the free fatty acid suppression
rate is calculated.
42. 4-Measurement of Insulin and Other Glucose-
Regulating Peptide Hormones
A - Amylin
•Amylin, also named islet amyloid polypeptide, is a
pancreatic islet peptide consisting of 37 amino acids
with a role in the maintenance of glucose
homeostasis.
43. •The peptide is predominantly present in the β-cells of
the pancreas and to a lesser extent in the
gastrointestinal tract and in the nervous system, where
amylin mRNA is also present along with specific binding
sites.
PURPOSE
AND
RATIONALE
Binding sites with high affinity for amylin are present in
several brain regions, with the nucleus accumbens and
surrounding tissue containing more than twice as many
banding sites as any other regions.
44. Procedure
Membranes are prepared from male Sprague-Dawley rats (150–200g).
Following decapitation ,the basal forebrain regions (nucleus accumbens) are
removed to PBS (pH 7.4) at 4°C
The tissues are weighted, then placed in 10ml/g tissue of ice-cold 20mM
HEPES/KOH (pH 7.4) and homogenized with a Polytron
45. An additional 30ml of cold HEPES/KOH is added, and the homogenate
centrifuged (48,000×g, 15min)
After discarding the supernatant fluid, membrane pellets are resuspended
by homogenization in 40ml of fresh HEPES/KOH and centrifuged as before.
Membranes are washed again by homogenization in buffer and
centrifugation.
46. The final membrane pellet is resuspended in a volume of 20mM
HEPES/KOH containing 0.2mM PMSF added immediately before use from
a stock 0.2M solution in ethanol.
A volume of buffer is used to yield a concentration of about 80mg original
tissue/ml.
Membranes are kept frozen at –80°C until use.
47. Binding assay
Membranes from 4mg of original wet weight of tissue are incubated with
125I-BH-amylin in 20mM HEPES/KOH (pH 7.4), containing:
0.5mg/ml bacitracin,
0.5mg/ml BSA and
0.2mM phenyl methyl sulfonyl fluoride (PMSF),
for 60min at 23°C.
Incubations are carried out in duplicate tubes and are started by addition
of membranes
48. Incubations are terminated by filtration through glass fiber filters that have
been presoaked in 0.3% polyethylene-imine, followed by washing with
15ml of cold PBS.
Competition curves are generated by measuring binding of
13pM 125I-BH-amylin in the presence of 10−11 to 10−6
unlabeled peptide. Data are fitted to a four parameter logistic
equation to derive half-maximal inhibitory concentrations(IC50
values)and slope factor.
EVALUATION
49. A - Insulin-Resistant Primary Rat Adipocytes
PURPOSE
AND
RATIONALE
• Primary rat adipocytes can be maintained
in culture for long-term treatment with
compounds/drug candidates to study their
insulin-like activity upon chronic challenge
or for the induction of insulin resistance.
5 - Insulin Target Tissues and Cells
50. Procedure
For induction of insulin resistance, primary rat adipocytes
are incubated in buffer S
25mM glucose, 0.5mM sodium pyruvate and 10nM insulin for 4 to 20h
at 37°C under slow shaking
51. When assayed for insulin-stimulated glucose transport following a
15- to 30-min incubation period in buffer S but lacking insulin
(which enables down regulation of the glucose transport system
from the chronically insulin stimulated to basal levels).
52. Evaluation
The adipocytes made insulin-resistant in vitro show a right-ward
shift of the concentration-response curve (decreased insulin
sensitivity) and a reduced maximal glucose transport velocity at
constant or only slightly elevated basal glucose transport
(decreased insulin responsiveness)
During prolonged incubation in suspension culture, the adipocytes
tend to increase their basal glucose uptake which might reflect
elevated energydemands due to stress conditions or loss of plasma
membrane integrity
53. It is therefore most critical to choose culture conditions which
preserve the energy status of the rat adipocytes and are
compatible with 5- to 6-fold stimulations of glucose transport, at
least, at low glucose concentrations corresponding to the normal
insulin sensitive state.
54. B – Primary rat hepatocytes
Sprague-Dawley rats (100–200g) are fed prior
to the hepatocyte isolation.
Hepatocytes are isolated from rat livers
thoroughly perfused with buffer containing
collagenase, hyaluronidase and trypsin
inhibitor.
The rat livers are perfused for 4min at
25ml/min flow rate with perfusion buffer
55. And then with collagenase buffer
until the digestion is complete
(∼6min).
At the end of the perfusion,
connective tissue and large blood
vessels are removed.
The hepatocytes are then passed
through a 100-µm nylon mesh
sieve.
56. The cells are washed twice with 125ml of wash buffer
and collected by centrifugation (50×g, 2min).
The hepatocytes are suspended in plating medium
(DMEM, 10% FBS, 100nM insulin, 25nM
dexamethasone, 6.3µg/ml transferrin, 22µg/l
gentamycin) and passed through a 100-µm nylon mesh
sieve.
Cells (1.6×105) are plated in 48-well cell culture
plates for the various metabolic assays.
57. 6 - Assays for Insulin and Insulin Like Metabolic
activity
A - Method Based on the Incorporation of
Radiolabeled Glucose
PURPOSE AND
RATIONALE
This assay measures the complete pathway of lipid
synthesis (lipogenesis) encompassing the transport of
the radiolabelelled glucose across the plasma membrane
of the adipocytes, its conversion into glycerol and/or
fatty acids and their subsequent esterification into
predominantly neutral TAG and phospholipids --
58. and finally the deposition of TAG in LD in the
cytoplasm of the adipocytes.
Since in adipocytes each of these steps is
stimulated by insulin, albeit to varying
degrees…….
the lipogenesis assay is perfectly suited for the
analysis of effects of compounds/drugs on the
complex insulin signaling cascade regulating
lipogenesis.
59. The cells are lysed and the total lipids separated from water-
soluble products and the incubation medium including the
unincorporated[3H]glucose by addition of toluene-based
scintillation cocktail.
For measurement of lipogenesis monitoring effects on both
glucose transport and esterification, isolated rat adipocytes are
incubated with D-[3H]glucose (0.55mM final concentration,0.1–
1µCi).
Procedure
60. The reaction is started by the transfer of 0.2ml of adipocyte suspension (3.5×105
cells/ml) in KRHB to scintillation vials containing 0.1ml of [3-3H] glucose
(2µCi/ml,4.4mM),0.4 ml of 2-fold KRHB and 0.3ml of insulin or compound/drug with
insulin-mimetic activity dissolved in vehicle (e.g. DMSO) and diluted with KRHB to the
appropriate concentration of compound and vehicle (e.g. 3% DMSO).
After phase separation, radioactivity incorporated in to total lipids/phospholipids is
determined by liquid scintillation counting directly without removal of the lipid
phase based on determination of the radiolabel of the lipidic products partitioned
into the toluene phase containing the scintillator rather than of the [3H]glucose
left in the aqueous phase lacking scintillator.
61. The 3H-radioactivity is determined with a liquid scintillation counter
The vials are mixed rigorously using a vortexer and subsequently left standing
for 2–4h to allow phase separation.
After incubation for 90min, the reaction is terminated by the addition of 10ml
of toluene-based scintillation cocktail.
The scintillation vials are placed under a stream of carbogen for 10s, then
closed and placed in a very slowly shaking water bath (37°C).
62. Evaluation
The blank values lacking adipocytes (usually500–600dpm) are subtracted from
the values measured for the corresponding set of test mixtures containing
adipocytes to correct for 3H-radiation originating from the aqueous phase (i.e.
[3H]glucose left in the incubation medium).
Fold stimulations reflecting the responsiveness of the glucose transport
and/or esterification systems of the adipocytes toward
insulin/compound/drug are calculated as ratio between the corrected test
values (presence of insulin/compound/drug)and basal values (absence of
insulin/compound/drug).
Typically, insulin induces 15to 20-fold, 8- to 12-fold and 2.5- to 4-fold
stimulations in lipogenesis at 50µM, 0.55mM and 2mM glucose, respectively.
63. Reference
•Appropriate insulin concentrations are
0.01,0.02,0.04,0.06,0.08,0.1,0,12,0.15,
0.2,0.5,1,5nM (final concentration in the assay).
•Typically, the EC50 for human insulin is 0.06–
0.10nM.
•The insulin-like activity of compounds/drugs can be
expressed as % of the maximal insulin stimulation
64. 7-Measurement of Glucose Absorption
Evaluation of Glucose Absorption In Vivo
PURPOSE AND
RATIONALE
The inhibition of glucose absorption can be
determined by measuring blood glucose
after administration of starch or
disaccharides with and without the inhibitor.
In addition, non-absorbed starch or
disaccharides can be determined in the
intestine.
65. Procedure
Male Wistar rats are kept on a standard diet with
free access to tap water at constant
temperature(24±1°C).
Sixteen hours prior to the experiment food but
not water is with held.
Groups of rats receive by stomach tube 2.5g/kg
raw starch in a water suspension without or
with various doses of the α-amylase inhibitor.
66. After 10, 20, 30, 60, 120and 240min, blood
is withdrawn for determination of blood
glucose and non-esterified fatty acids.
The animals are sacrificed after these
intervals and the residual starch in the
stomach and the intestine determined.
Definitely more starch is found in the
intestine after simultaneous application of
the α amylase inhibitor.
67. Evaluation
•The values of starch content in stomach and
intestine, as well as the blood glucose-, serum
insulin and NEFA-values are compared between
control and treated animals.
68. 8- Monitoring of Diabetic Late
Complications
Electro-retinogram
PURPOSE AND
RATIONALE
Diabetic neuropathy is one of the important
symptoms of long-lasting diabetes. Several animal
studies with aldose reductase inhibitors have been
performed. Segawa and coworkers measured the
development of electro-retinogram abnormalities
and the possible role of polyol pathway activity in
diabetic hyperglycemia and galactosemia in the
rat.
69. Procedure
Using a contact lens-type electrode, electro-retinograms (ERG) evoked by strong flushes are
amplified by a preamplifier, displayed on an oscilloscope and summed using a signal averager
which also provides a copy of the averaged ERG.
Photic stimulation is delivered with an intensity of one J in 20s interstimulus intervals.
Electroretinography is performed monocularly with the pupil maximally dilated.
Male Sprague-Dawley rats weighing 310–400g are dark-adapted for 20min and anesthetized with
i.p injections of ketamine, 50–80mg/kg and atropine sulfate, 2mg/kg.
70. For inducing galactosemia, male Sprague-Dawley rats weighing 140–185g at the beginning
of the study, receive a diet of 30% galactose. Test compounds are given as 0.1% to the diet.
The sum of these amplitudes is expressed as the wavelet index.
The oscillatory potentials (designated O1,O2, and O3 in order of appearance on the
ascending limb of the b-wave) are added together.
The peak latencies are measured as the intervals between the stimulus onset and the peak
of the corresponding a- and b-waves and oscillatory potentials.
Theamplitudesofthe oscillatory potentials are measured.
The amplitudes of the a- and b-waves are measured from the base line to the trough of the
a-wave and from the trough of the a-wave to the crest of the b-wave, respectively.
71. Evaluation
•Data are calculated as mean ± SEM and significance
levels are estimated using the Wilcoxon rank sum
test for unpaired data (two-sided).
•Linear regression is calculated by the least square
method. A p-value of <0.05 is regarded as
statistically significant.
72. 9- Insulin Analogs: Assessment of
Insulin Mitogenicity and IGF-I Activity.
A- Introduction and Application to Insulin
Analogs
PURPOSE AND
RATIONALE
The structure and approach to the evaluation of new
insulins is directed towards efficacy in terms of
glucose lowering, in the predictive manner to
differentiate between monomeric insulins with fast
absorption kinetics and long acting insulins with
delayed absorption from the subcutaneous injection
site.
73. PROCEDURE
The initial steps are performed in vitro, focused on receptor interaction.
Subsequent steps in-vitro to explore the receptor-mediated
signaling, which is however at the present time difficult to attribute
precisely to biological and clinical effects.
The main aim of the in vitro evaluation is to establish the relation of
metabolic activity to mitogenic activity, as previously done for structure
activity studies on insulin analogs, and subsequently directed to predicting
clinical relevance of these observations, when comparing new compounds
with the established biochemical and toxicological profile of [B10-Asp]
insulin, and the clinically used fast acting and long acting insulin analogs.