MULTIPLE DRUG RESISTANCE

MULTIPLE DRUG RESISTANCE

Contents

Preface

Chapter I Profile of Genetic and Cellular Multiple Drug Resistance in a Diagnostic and Therapeutic Strategy in Acute Leukemia in Children and Adults

Abstract

Drug Resistance and Therapy Failure in Acute Leukemia

Mechanisms of Cellular Drug Resistance

Biology of Acute Lymphoblastic Leukemia in Age Groups

Biology of Acute Myeloid Leukemia in Age Groups

Cytogenetics and In Vitro Drug Resistance in Acute Leukemia in Children and Adults

In Vitro Drug Resistance Profile in ALL Subgroups

In Vitro Drug Resistance Profile of Philadelphia Positive Acute Lymphoblastic Leukemia is Heterogeneous and Related to Age

In Vitro Drug-Resistance Profile in Infant Acute Lymphoblastic Leukemia in Relation to Age, MLL Rearrangements and Immunophenotype

TEL/AML1 Gene Fusion is Related to In Vitro Drug Sensitivity for L-Asparaginase in Childhood Acute Lymphoblastic Leukemia

Translocation t(1;19) and In Vitro Drug Resistance

DNA Hyperdiploidy and In Vitro Drug Resistance

Drug Resistance to Methotrexate in Therapy of ALL

In Vitro Drug Resistance Profile in AML Subgroups

Cellular Drug Resistance Profiles in Childhood Acute Myeloid Leukemia: Differences between FAB Types and Comparison with Acute Lymphoblastic Leukemia

Cellular Drug Resistance in Childhood Acute Myeloid Leukemia is Related to Chromosomal Abnormalities

Possibility of Modulation of Drug Resistance In Leukemia

Clinical Aspects of Cellular Drug Resistance in ALL between Children and Adults

Clinical Aspects of Cellular Drug Resistance in AML between Children and Adults

Comparison of Drug Resistance in Different Types of Leukemia in Children and Adults

Profile of Genetic and Cellular Multiple Drug Resistance in a Diagnostic and Therapeutic Strategy in acute Leukemia in Children and Adults

Principles of Microarray Technology

Application of Microarray

Prediction of Outcome Based on Expression Signatures

Drug Resistance in Leukemia Microarray Studies

Analysis of Gene Expression Profiles in Relapsed ALL

Conclusion

Acknowledgments

References

Chapter II Multidrug- Resistant Acinetobacter baumannii Infections: Characteristics and Treatment Options

Introduction

Microbiological Characteristics

Epidemiology

Antimicrobial Resistance

Mechanisms of Resistance

Resistance to Beta-Lactams

Resistance to Aminoglycosides

Resistance to Quinolones

Resistance to Tetracyclines

Resistance to Polymyxins

Virulence and Pathogenicity

Antibiotic Useful on Acinetobacter Infections

Carbapenems

Colistin

Sulbactam

Glycylcyclines

Aminoglycosides

Fluoroquinolones

Combination Therapy

Specific Infections due to A. Baummanii

1. Nosocomial Infections

Nosocomial meningitis

Hospital acquired/ventilator associated pneumonia (VAP)

Bloodstream infections

2. Community-Acquired Infections

Infection control and prevention

Bibliography

Chapter III Multiple Drug Resistance

Abstract

1. Introduction

2. Molecular and Cellular Mechanisms of Bacterial Resistance

2.1. Inhibition of Synthesis of Microbial Cell Wall

2.1.1. Inhibition of DNA synthesis or function

2.1.2. Inhibition of synthesis of bacterial proteins

2.1.3. Lesion or destruction of microbial membranes

2.2. Mechanisms of Antimicrobial Resistance

2.3. Genetic Determinants for Resistance

2.3.1. Integrons

2.3.2. Plasmids

2.3.3. Transposons

2.4. Multi-Drug Resistance and Cross-Resistance

2.5. Expression of Resistance to Specific Agents

2.5.1. Resistance to sulphonamides

2.5.2. Resistance to Quinolones

2.5.3. Resistance to Aminoglycosides

2.5.4. Resistance to Tetracycline

2.5.5. Resistance to Beta-Lactam Antibiotics

3. Some Overlooked Aspects Concerning Development and Spread of Antimicrobial Resistance

3.1. Patients’ Contribution to Antimicrobial Misuse

3.2. Impact of Industrial Antimicrobial Production and Hospital Effluent on the Spread of Resistance

3.3. Role of Pets as Reservoirs of Resistant Bacteria

3.4. Environmental Reservoirs of Antimicrobial Resistance Genes

4. Multidrug Resistance in Specific Organisms in Jamaica

4.1 Staphylococcus aureus

4.2. Enterobacteria

4.3. Pseudomonas aeruginosa

4.4. Stenotrophomonas maltophilia

5. Conclusion

6. References

Chapter IV Herb-Drug Interactions and Implication in Drug Monitoring

Abstract

1. Introduction

2. Properties of Drugs that Interact or do not Interact with Herbs

2.1. Drugs Reported to Interact with Herbs

2.2. Drugs Reported Not to Interact with Herbs

3. Potential Mechanisms for Herb-Drug Interactions

3.1. Pharmacokinetic Mechanisms

3.2. Pharmacodynamic Mechanisms

4. Clinical Outcomes of Drug-Herb Interactions

4.1. Altered Drug Pharmacokinetics

4.2. Altered Drug Efficacy

4.3. Toxicity Concerns

5. Strategy for Eliminating Toxicity Arising from Drug-Herb Interactions

5.1. Predicting Herb-Drug Interactions

5.2. Timely Identification of Drugs that Interact with Herbs

5.3. Therapeutic Drug Monitoring

6. Conclusions and Future Perspectives

Abbreviations

References

Chapter V Cell Membranes, Cytosolic pH and Drug Transport in Cancer and MDR: Physics, Biochemistry and Molecular Biology

Abstract

Introduction

A. The Role of pH in Cancer and MDR: An Overview

B. pHi and Multiple Drug Resistance (MDR) to Anticancer Drugs

C. Weighing the Role of Drug Handling and Extrusion by Transporters against Changes in Cytosolic pH

D. The “Vacuum Cleaner” Hypothesis: A Model in Need of Clarification

I. The Physical Biology of MDR

A. The Role of Physical, Chemical, and Mechanical Factors Affecting the Transverse Movement of Drugs Across the Cell Membrane

B. The Critical Relationship between The Two Dimensional (2D) Random Walk Of Membrane –Embedded Drugs and Pgp-Like Transporter Surface Density in Mediating MDR

C. Determination of the Drug Influx into MDR Cells

II. The Role of Drug Size in MDR

Bielder and Riehm’s Seminal 1970’s Study: Proof That the Membrane’s Mechanical Properties Are Central to MDR

III. The Role of pHi in MDR

A. Why Would the pHi be an Important Factor in a Cell Membrane’s Mechanical Properties?

B. Fundamental Relationship between pH and MDR Levels

C. Drug Handling Versus Cytosolic pH: Relative Involvement of Each

Conclusion

References

Chapter VI Genetic and Clinical Factors of Antibiotic Resistance in Bacteria

Abstract

Introduction

The Modes of Antibiotic Action

1. Interference with cell wall synthesis (6,7)

2. Inhibition of protein synthesis (6,8)

3. Interference with nucleic acid synthesis (6)

4. Inhibition of a metabolic pathway (6)

5. Disorganization of the cell membrane (9,10)

What is Antibiotic Resistance?

Natural and Acquired Antibiotic Resistance

Mechanisms of Antibiotic Resistance

Antibiotic Resistance and Food

Virulence and Antibiotic Resistance of the Genome of Four of the Most Threatening Microorganisms

a. Staphylococcus aureus

b. Acinetobacter baumannii

c. Pseudomonas aeruginosa

d. Klebsiella pneumoniae

e. Providenzia stuartii

Antibiotic Exposure and Factors of Cross-Transmission

Conclusion

References

Chapter VII Bacteriophage Therapies and Enzybiotics: Novel Solutions to Antibiotic Resistance

Abstract

1. Introduction

2. Bacteriophages and Bacteriophage Therapies

2.1. Classification of Phages

2.2. Mode of Action

2.3. Antibacterial Efficacy of Phages

2.4. Specificity of Phage Therapy

2.5. Bacterial Resistance to Phages

2.6. Advantages and Disadvantages of Phage Therapy

3. Enzybiotics: Bacterial Cell Wall Hydrolases (BCWHs) as Novel Alternatives to Antibiotics

3.1. BCWHs from Different Sources

3.1.1. Lysozymes

3.1.2. Microlysins

3.1.3. Virolysins

3.2. Mode of Action

3.3. Antimicrobial Efficacy of BCWHs

3.4. Bacterial Resistance to BCWHs

3.5. Prephylaxis using BCWHs

4. Virolysins: Promising Enzybiotics

4.1. General Description of Virolysins

4.2. Antibacterial Efficacy of Virolysins

4.2.1. Virolysins against streptococcal bacteria

4.2.2. Virolysins against cariogenic bacteria

4.2.3. Virolysins against staphylococcus

4.2.4. Virolysins against bacilli

4.2.5. Virolysins against enterococcus species

4.2.6. Virolysins against salmonella

4.2.7. Virolysins against clostridium

4.3. Production of Virolysins

5. Conclusion Remarks

Acknowledgment

References

Chapter VIII Nutrition and Tuberculosis

Abstract

Introduction

Nutrition and Risk of Tuberculosis

Diabetes Mellitus

Severity of Disease

Response to Treatment

Nutritional Supplementation

Other Adjunctive Therapy

Reference

Chapter IX Reversal of Multidrug Resistance (MDR) by the Isoquinoline Alkaloid Glaucine

Abstract

1. Introduction

2. Materials and Methods

2.1. Chemicals

2.2. Cell Culture

2.3. Mitoxantrone Efflux assay

2.4. Flow Cytometry Analysis

2.5. Rhodamine 123 Efflux Assay

2.6. Cytotoxicity Assay

2.7. Data Analysis

3. Results

3.1. Mitoxantrone Efflux Assay in MDA-MB-231pcDNA3-BCRP-Clone23

3.2. Flow Cytometry Analysis in CEM ADR5000

3.3. Rhodamine 123 Efflux Assay in Caco-2 Cells

3.4. Cytotoxicity Assay

4. Discussion

Acknowledgments

References

Chapter X Uncommon Acinetobacter Baumannii Isolation from Leukemic Patients and Emerging of Tigecycline-Resistance

Abstract

Funding

Acknowledgments

Transparency Declarations

References

Chapter XI Finding the Genetic Solution for Cancer in the Mechanism of Taxol Cytotoxicity

Abstract

Introduction

References

Chapter XII Genetic Regulation, Physiology, Assessment and Inhibition of Efflux Pumps Responsible for Multi-Drug Resistant Phenotypes of Bacterial Pathogens

Abstract

Introduction

Efflux Pumps of MDR Bacteria: The Major Facilitator Superfamily

The NorA Efflux Pump of Staphylococcus Aureus

Other Intrinsic Efflux Pumps of Gram-Positive Bacteria

Efflux Pumps of Gram-Negative Bacteria: The Resistance Nodulation Division (RND) Family

Genetic Regulation of Efflux Pumps of Gram-Negative Bacteria (ex. Escherichia coli)

Evaluation of Intrinsic and Over-Expressed Efflux Pumps of Gram-Negative Bacteria

Summary and Perspectives

References

Chapter XIII Antimicrobial Resistance: Evolutionary Roots

References

Chapter Sources

Index

Blank Page