The International Conference of Harmonization (ICH) has worked on har- nizing the stability regulations in the US, Europe, and Japan since the early 1990s. Even though the Stability Guidelines Q1A (R2) was issued over a decade ago, issues surrounding this arena continue to surface as the principles described in the guideline are applied to different technical concentrations. As a result, the stability community has continued to discuss concerns and find ways of harmonizing regulatory requirements, streamlining practices, improving processes in order to bring safe and effective medical supplies to the patients around the world. In 2007, the American Association of Pharmaceutical Scientists (AAPS) Stability Focus Group organized two workshops - the Stability Workshop and the Degradation Mechanism Workshop. These meetings attracted many industry scientists as well as representatives from several regulatory agencies in the world to discuss important topics related to pharmaceutical stability practices. Recognizing the importance of documenting these discussions and with the permission of AAPS, I have worked with speakers to assemble a collection of 30 articles from presentations given at these two meetings, mainly the Stability Workshop. I trust that this book will be beneficial to all of you in providing guidance and up-to-date information for building quality stability programs. v Freedom of our mind is Mother of all inventions.

Established in 1960, Advances in Heterocyclic Chemistry is the definitive serial in the area--one of great importance to organic chemists, polymer chemists, and many biological scientists. Every fifth volume ofAdvances in Heterocyclic Chemistry contains a cumulative subject index.
Key Features
* A selection of topics covered in Volume 62
* Synthesis possibilities in "N"-Fluoropyridinium salts
* An updated review of Pyran Chemistry
* The organic chemistry and synthesis of Tetrathia- and tetraselena-fulvalenes
* A review of the classes of five-membered heterocyclic rings containing two sulfur and two nitrogen atoms, both as anionic and radical species

This book addresses the phenomenology, demographics, and neurobehavioral aspects of suicidal behavior and its risk factors, underscoring common neurobehavioral threads among different approaches which may underlie such extreme behavior. It additionally provides an overview of new approaches, such as imaging techniques to identify at-risk individuals or in response to drug treatment associated with suicidal behavior, neurodevelopmental approaches, genetic and epigenetic linkages to suicidal behavior, animal models of specific risk factors, as well as potential biomarkers being employed to help assess risk.

Theintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZoTheintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZollner ThePharmacologyofVoltage-GatedSodiumChannels inSensoryNeurones ...519 ReginaldJ. DochertyandClareE. Farmer RoleofCalciuminRegulatingPrimarySensory NeuronalExcitability ...563 T. D. Gover,T. H. MoreiraandD. Weinreich FutureTreatmentStrategiesforNeuropathicPain...589 FabienMarchand,NicholasG. JonesandStephenB.

The book covers theoretical background and methodology as well as all current applications of Quantitative Structure-Activity Relationships (QSAR). Written by an international group of recognized researchers, this edited volume discusses applications of QSAR in multiple disciplines such as chemistry, pharmacy, environmental and agricultural sciences addressing data gaps and modern regulatory requirements. Additionally, the applications of QSAR in food science and nanoscience have been included - two areas which have only recently been able to exploit this versatile tool. This timely addition to the series is aimed at graduate students, academics and industrial scientists interested in the latest advances and applications of QSAR.

"Neurological Disorders" is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for neurological disorders such as neurofibromatosis, Alzheimer s disease, Parkinson s disease, Huntington disease, ALS, and the epilepsies. "Neurological Disorders "has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. The aim of this series of volumes on "Animal and Translational Models for CNS Drug Discovery" is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery.

This is the second volume in the three volume-set, "Animal and Translational Models for CNS Drug Discovery" 978-0-12-373861-5, which is also available for purchase individually.
- Clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery process
- Critical evaluation of animal and translational models improving transition from drug discovery and clinical development
- Emphasis on what results mean to the overall drug discovery process
- Exploration of issues in clinical trial design and conductance in each therapeutic area"

"Psychiatric Disorders" is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for psychiatric disorders such as anxiety, obsessive-compulsive disorder, depression, schizophrenia, bipolar disorder, ADHD, and autistic spectrum disorder. "Psychiatric Disorders "has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. The aim of this series of volumes on "Animal and Translational Models for CNS Drug Discovery" is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery.

This is the first volume in the three volume-set, "Animal and Translational Models for CNS Drug Discovery" 978-0-12-373861-5, andis also available for purchase individually.
Provides clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery processCritical evaluation of animal and translational models improving transition from drug discovery and clinical developmentEmphasizes what results mean to the overall drug discovery processExplores issues in clinical trial design and conductance in each therapeutic areaPsychiatric Disorders is available for purchase individually."

"Reward Deficit Disorders" is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for reward deficit disorders such as alcohol dependence, nicotine dependence, heroin and cocaine addiction, obesity, and gambling and impulse control disorders. "Reward Deficit Disorders "has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. "Reward Deficit Disorders" also has a section dedicated to the specifics of the regulatory aspects to abuse liability testing. The aim of this series of volumes on "Animal and Translational Models for CNS Drug Discovery" is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery.

This is the third volume in the three volume-set, "Animal and Translational Models for CNS Drug Discovery" 978-0-12-373861-5, which is also available for purchase individually.
Provides clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery processCritical evaluation of animal and translational models improving transition from drug discovery and clinical developmentEmphasizes what results mean to the overall drug discovery processExplores issues in clinical trial design and conductance in each therapeutic areaNeurological Disorders is available for purchase individually.

Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental.

Articles written by leading investigators in the field
Informs and updates on all the latest developments

Inflammation has invaded the field of psychiatry. The finding that cytokines are elevated in various affective and psychotic disorders brings to the forefront the necessity of identifying the precise research domain criteria (RDoCs) that inflammation is responsible for. This task is certainly the most advanced in major depressive disorders. The reason is that a dearth of clinical and preclinical studies has demonstrated that inflammation can cause symptoms of depression and conversely, cytokine antagonists can attenuate symptoms of depression in medical and psychiatric patients with chronic low grade inflammation. Important knowledge has been gained on the symptom dimensions that inflammation is driving and the mechanisms of action of cytokines in the brain, providing new targets for drug research and development. The aim of the book "Inflammation-Associated Depression" is to present this field of research and its implications in a didactic and comprehensive manner to basic and clinical scientists, psychiatrists, physicians, and students at the graduate level.

Product information not available.

The demand for traditional medicines, herbal health products, herbal pharmaceuticals, nutraceuticals, food supplements and herbal cosmetics etc. is increasing globally due to the growing recognition of these products as mainly non-toxic, having lesser side effects, better compatibility with physiological flora, and availability at affordable prices. In the last century, medical science has made incredible advances all over the globe. In spite of global reorganization and a very sound history of traditional uses, the promotion of traditional medicine faces a number of challenges around the globe, primarily in developed nations. Regulation and safety is the high concern for the promotion of traditional medicine. Quality issues and quality control, pharmacogivilane, scientific investigation and validation, intellectual property rights, and biopiracy are some key issues that restrain the advancement of traditional medicine around the globe. This book contains diverse and unique chapters, explaining in detail various subsections like phytomolecule, drug discovery and modern techniques, standardization and validation of traditional medicine, and medicinal plants, safety and regulatory issue of traditional medicine, pharmaceutical excipients from nature, plants for future. The contents of the book will be useful for the academicians, researchers and people working in the area of traditional medicine.

Drug discovery originating in Africa has the potential to provide significantly improved treatment of endemic diseases such as malaria, tuberculosis and HIV/AIDS. This book critically reviews the current status of drug discovery research and development in Africa, for diseases that are a major threat to the health of people living in Africa. Compiled by leading African and international experts, this book presents the science and strategies of modern drug discovery. It explores how the use of natural products and traditional medicines can benefit from conventional drug discovery approaches, and proposes solutions to current technological, infrastructural, human resources, and economic challenges, which are presented when attempting to engage in full-scale drug discovery. Topics addressed are varied; from African medicinal plants to marine bioprospecting, pharmacogenetics and the use of nanotechnology. This book brings together for the first time a collection of strategies and techniques that need to be considered when developing drugs in an African setting. It is an unprecedented and truly international effort, highlighting the remarkable effort made so far in the area of drug discovery research by African scientists, and scientists from other parts of the world working on African health problems.

Parkinson s disease is the second most prevalent neurodegenerative disease and is characterized by the irreversible loss of dopamine neurons. Despite its high prevalence in society and many decades of research, the origin of the pathogenesis and the molecular determinants involved in the disorder has remained elusive. Confounding this issue is the lack of experimental models that completely recapitulate the disease state. The identification of a number of genes thought to play a role in the cell death, and development of both toxin and genetic models to explore the function of the genes both in unaffected and diseased cells are now providing new insights into the molecular basis of the neurodegeneration, as well as therapeutic approaches. In this reference, we will describe the advances and the advantages that various invertebrates, cell culture, rodents, and mammals provide in the identification of the molecular components and mechanisms involved in the cell death, and outline the opportunities that these systems provide in drug discovery.
* Comprehensive and critical assessment of the utility of various model systems to identify the molecular components and pathways involved in Parkinson s disease
* Describes the power of toxin and genetic models to identify novel therapeutic targets and compounds that can be used in PD
* Current overviews of current status of PD research and discovery from bench-to-bedside
* Provides novel insights and views on where the future of PD research may lead
* Provides a powerful teaching tool and template to explore the utility of model systems to identify molecular pathways, molecular targets, and therapeutics that are applicable to a variety of neurological diseases"

This book systematically covers immunoassays for food, presenting detailed approaches such as antigen design, food matrix pre-treatment and detection format optimization for 9 classes of food hazards and nutrition constituents. Offering ideas on how to improve the efficiency of recognized xenobiotics and food contents, this practical book also describes the discovery and utilization of novel immune agents like aptamer and molecular imprinted polymers in food analysis. It is intended for a broad range of areas, including biologists and food chemists, and is sure to become a key reference resource for students and professionals alike.

This volume collects a variety of techniques and methodologies developed to facilitate research on integrin biology and to identify ideal targets and approaches for the treatment of multiple organ diseases, with a focus on cancer in particular. The chapters consecutively describe the tools for structural analysis, identification and detection of integrins as biomarkers, and include thorough laboratory and clinically-related methods on different strategies for generation, synthesis and evaluation of probes, carriers, peptides or small particles for integrin targeting, imaging, and drug delivery. As part of the Methods in Pharmacology and Toxicology series, this book contains the practical details that are invaluable in the laboratory. Authoritative and advantageous, Integrin Targeting Systems for Tumor Diagnosis and Therapy serves readers from a wide spectrum, including researchers and students seeking an overview of existing developments, as well as leading professionals aiming to become more familiar with integrin-related innovative technologies in cancer research.

Traditional medicinal knowledge, especially the use of ethnomedicinal plants in developing countries, has been passed down for generations. Today, however, scientists are poised to combine traditional medicinal plants and modern drug discoveries to further develop essential products that have followed the leads of indigenous cures used for centuries. Ethnomedicinal Plant Use and Practice in Traditional Medicine provides emerging research exploring the theoretical and practical aspects of indigenous knowledge and therapeutic potential within ethnobotany. Featuring coverage on a broad range of topics such as drug discovery, traditional knowledge, and herbal medicine, this book is ideally designed for doctors, healers, medical professionals, ethnobotanists, naturalists, academicians, researchers, and students interested in current research on the medical use and applications of natural-based resources.

1. Application of Transgenic and Gene-Targeted Mice to Dissect Mechanisms of Lung Disease.- Emphysema.- 2. Models of Genetic Emphysema: The C57B1/6J Mice and their Mutants: Tight-Skin, Pallid and Beige Giuseppe Lungarella, Eleonora Cavarra and.- 3. ?1-Antitrypsin Deficiency.- 4. Recombinant SLPI: Emphysema and Asthma.- 5. Elastase Inhibitors in the Lung: Expression and Functional Relationships.- 6. Regulation of Neutrophil Proteinases.- 7. Control of Connective Tissue Genes.- Infection.- 8. Genetic Models of Bacterial Lung Infection.- 9. Genetics of Bacteria: Role in Pathogenesis of Infection of the Respiratory Tract.- 10. Polymerase Chain Reaction in the Diagnosis of Respiratory Tract Infections.- 11. Cystic Fibrosis.- 12. Respiratory Bacterial Infections in Patients with Cystic Fibrosis: Pathogenicity and Implications for Serine Proteinase Inhibitor Therapy.

This book addresses the therapeutic strategies to target mitochondrial metabolism in diseases where the function of that organelle is compromised, and it discusses the effective strategies used to create mitochondrial-targeted agents that can become commercially available drug delivery platforms. The consistent growth of research focused in understanding the multifaceted role of mitochondria in cellular metabolism, controlling pathways related with cell death, and ionic/redox regulation has extended the research of mitochondrial chemical-biological interactions to include various pharmacological and toxicological applications. Not only does the book extensively cover basic mitochondrial physiology, but it also links the molecular interactions within these pathways to a variety of diseases. It is one of the first books to combine state-of-the-art reviews regarding basic mitochondrial biology, the role of mitochondrial alterations in different diseases, and the importance of that organelle as a target for pharmacological and non-pharmacological interventions to improve human health. The different chapters highlight the chemical-biological linkages of the mitochondria in context with drug development and clinical applications.

The suspension dosage form has long been used for poorly soluble active ingre- ents for various therapeutic indications. Development of stable suspensions over the shelf life of the drug product continues to be a challenge on many fronts. A good understanding of the fundamentals of disperse systems is essential in the development of a suitable pharmaceutical suspension. The development of a s- pension dosage form follows a very complicated path. The selection of the proper excipients (surfactants, viscosity imparting agents etc.) is important. The particle size distribution in the finished drug product dosage form is a critical parameter that significantly impacts the bioavailability and pharmacokinetics of the product. Appropriate analytical methodologies and instruments (chromatographs, visco- ters, particle size analyzers, etc.) must be utilized to properly characterize the s- pension formulation. The development process continues with a successful scale-up of the manufacturing process. Regulatory agencies around the world require cli- cal trials to establish the safety and efficacy of the drug product. All of this devel- ment work should culminate into a regulatory filing in accordance with the regulatory guidelines. Pharmaceutical Suspensions, From Formulation Development to Manufacturing, in its organization, follows the development approach used widely in the pharmaceutical industry. The primary focus of this book is on the classical disperse system - poorly soluble active pharmaceutical ingredients s- pended in a suitable vehicle.

Reports on the emergence and prevalence of resistant bacterial infections in hospitals and communities raise concerns that we may soon no longer be able to rely on antibiotics as a way to control infectious diseases. Effective medical care would require the constant introduction of novel antibiotics to keep up in the "arms race" with resistant pathogens. This book closely examines the latest developments in the field of antibacterial research and development. It starts with an overview of the growing prevalence of resistant Gram-positive and Gram- negative pathogens, including their various resistance mechanisms, prevalence, risk factors and therapeutic options. The focus then shifts to a comprehensive description of all major chemical classes with antibacterial properties, their chemistry, mode of action, and the generation of analogs; information that provides the basis for the design of improved molecules to defeat microbial infections and combat the emerging resistances. In closing, recently developed compounds already in clinical use, those in preclinical or first clinical studies, and a number of promising targets to be exploited in the discovery stage are discussed.