University Of Health Sciences And Pharmacy In St Louis

DEVELOPMENT OF ROR LIGANDS FOR TREATMENT OF CIRCADIAN RHYTHM DISORDERS

SMART POLYMER FIBERS FOR TAMPON-LIKE NONSTEROIDAL CONTRACEPTIVE DEVICES - PROJECT SUMMARY/ABSTRACT NATURAL FERTILITY REQUIRES SPERMATOZOA TO MIGRATE THROUGH VISCOELASTIC SECRETIONS AND TO OVERCOME THE PHYSIOLOG- ICAL ACIDIC ENVIRONMENT OF THE FEMALE REPRODUCTIVE TRACT. OUR PRELIMINARY DATA SHOW THAT NOVEL MUCOADHESIVE, BIORESPONSIVE POLYMER COMPOSITIONS MAINTAIN A PHYSIOLOGICALLY ACIDIC PH ENVIRONMENT UPON EXPOSURE TO SEMINAL FLUID AND, AT THE SAME TIME, DRAMATICALLY INCREASE VISCOELASTIC PROPERTIES, WHICH NEGATIVELY IMPACTS SPERM MOTIL- ITY. THEREFORE, IT IS HYPOTHESIZED THAT - UPON EXPOSURE TO SEMEN - THE NOVEL MUCOADHESIVE, BIORESPONSIVE COM- POSITION RAPIDLY TRANSFORMS THE VAGINAL CAVITY INTO AN INHOSPITABLE ENVIRONMENT FOR SPERM. WE PROPOSE TO EXPLORE AN INNOVATIVE APPROACH TO ON-DEMAND NON-STEROIDAL CONTRACEPTION FOR WOMEN USING SMART (= SYSTEM MUTE UNTIL ACTIVATION BY A REMOTE TRIGGER) POLYMER FIBERS THAT MAINTAIN A PHYSIOLOGICAL, PROTECTIVE VAG- INAL ENVIRONMENT UPON EXPOSURE TO SEMINAL FLUID RESULTING IN INFERTILITY. THIS HIGH-RISK/HIGH-REWARD RESEARCH STRATEGY IS FUNDAMENTALLY DIFFERENT FROM CONVENTIONAL NONSTEROIDAL CONTRACEPTIVE METHODS AS IT REPRESENTS AN INNOVATIVE BIOENGINEERING CONCEPT INTENDED TO REACH THE HUMAN TESTING PHASE (I.E., IND MILESTONE) MUCH FASTER AND AT A LOWER COST THAN CONVENTIONAL DEVELOPMENT PROGRAMS FOCUSING ON MEDICINAL CHEMISTRY APPROACHES. IN THE R61 PHASE, WE WILL TEST WHETHER NON-WOVEN FIBER MATS COMPRISED OF BIORESPONSIVE POLYMER MIXTURES ESTABLISH AN ACIDIC MUCOADHESIVE GEL PHASE UPON EXPOSURE TO VAGINAL FLUID THAT MAINTAINS A PHYSIOLOGICALLY PRO- TECTIVE HIGHLY VISCOUS, ACIDIC MILIEU IN THE PRESENCE OF SEMEN, THEREBY INHIBITING SPERM MOTILITY TO A LEVEL CON- SISTENT WITH INFERTILITY. THE FEASIBILITY OF THIS APPROACH HAS BEEN SHOWN USING POLYMERIC FIBER MATS PRODUCED BY ELECTROSPINNING THAT DEMONSTRATED RAPID CONVERSION INTO A GEL PHASE, WHICH MAINTAINED ACIDIC PROPERTIES UPON EXPOSURE TO ALKALINE SEMINAL FLUID WHILE, SIMULTANEOUSLY, INCREASING 5-FOLD IN VISCOSITY. IN AIM #1, WE WILL DELINEATE ELECTROSPINNING FABRICATION PARAMETERS REQUIRED TO PREPARE DRY, NON-WOVEN FIBER MATS THAT EXHIBIT DESIRED MUCO- ADHESIVE AND BIORESPONSIVE PROPERTIES. WE WILL TEST THEIR ABILITY TO RAPIDLY RECONSTITUTE INTO AN ACIDIC GEL PHASE AND MAINTAIN EFFECTIVE PHYSICAL AND CHEMICAL BARRIERS PROPERTIES FOR HUMAN SPERM THAT ARE CONSISTENT WITH INFER- TILITY. IN AIM #2, WE WILL DEFINE SAFETY RISKS OF NON-WOVEN POLYMERIC FIBER MATS FOR NONSTEROIDAL CONTRACEPTION. WE WILL ASSESS WHETHER POLYMERIC FIBER MATS ARE TOXIC TO CELLS OF THE FEMALE REPRODUCTIVE TRACT. IN ADDITION, WE WILL EXPLORE HUMAN FACTORS THAT CONTRIBUTE TO USE-RELATED SAFETY AND EFFICACY RISKS USING INTERNET SURVEYS. THE R33 PHASE WILL BE INITIATED ONLY IF QUANTITATIVE MILESTONES DEFINED FOR THE R61 PHASE ARE MET. IN AIM #3, WE WILL REFINE ELECTROSPINNING FABRICATION PROCESS AND PERFORM A MORE RIGOROUS IN VITRO SAFETY ASSESSMENT THAT INCLUDES INTER- ACTIONS WITH THE VAGINAL MICROBIOME. IN THE FINAL AIM #4, WE WILL DETERMINE THE SAFETY, TOLERABILITY, AND CONTRACEP- TIVE EFFICACY OF THE MOST PROMISING POLYMER COMPOSITION IN VIVO USING THE RABBIT ANIMAL MODEL.

STLCOP HEERF FUNDS-INSTITUTION PORTION

ERRGAMMA AGONISTS TO TREAT MUSCULAR DYSTROPHY

STLCOP HEERF FUNDS-STUDENT PORTION

REV-ERB ANTAGONISTS FOR TREATMENT OF MUSCLE INJURIES

PHARMACOLOGICAL PROBES BASED ON MITRAGYNINE PSEUDOINDOXYL

DEFINING DYNORPHIN-CRF CIRCUITS IN STRESS AND NICOTINE BEHAVIORS

MULTIPURPOSE DEVICE FOR FEMALE-INITIATED NONSTEROIDAL ON-DEMAND CONTRACEPTION - PROJECT SUMMARY/ABSTRACT THE CHALLENGE OF THE FUTURE IS TO DEVELOP INNOVATIVE, FEMALE-INITIATED CONTRACEPTIVE TECHNOLOGIES THAT ARE AFFORD- ABLE, SOCIALLY ACCEPTABLE, AND PROVIDE DESIRED PROTECTION FROM UNINTENDED PREGNANCY WITHOUT EXPOSING WOMEN TO ADDITIONAL HEALTH RISKS ASSOCIATED WITH SYSTEMIC DISTRIBUTION OF CONTRACEPTIVE HORMONES. OUR PRELIMINARY DATA DEMONSTRATE DISCOVERY OF DRUG-FREE, BIORESPONSIVE POLYMER COMPOSITIONS THAT DRAMATICALLY INCREASE IN VISCOSITY UPON EXPOSURE TO SEMEN, THEREBY EFFECTIVELY PREVENTING PREGNANCY IN VIVO. IN AN EXPANSION OF THIS PIONEERING SMART (= SYSTEM MUTE UNTIL ACTIVATION BY A REMOTE TRIGGER) POLYMER CONCEPT, WE PROPOSE A NOVEL DELIVERY TECHNOLOGY USING AN ON-DEMAND DUAL-COMPARTMENT VAGINAL DEVICE THAT ENABLES WOMEN TO FORTIFY THE NAT- URAL CONTRACEPTIVE BARRIERS AT THE CERVICOVAGINAL JUNCTION WITHOUT PHARMACOLOGICAL ACTION OF DRUG MOLE- CULES. THIS HIGH-RISK/HIGH-REWARD RESEARCH STRATEGY IS FUNDAMENTALLY DIFFERENT FROM CONVENTIONAL NONSTEROIDAL CONTRACEPTIVE METHODS AS IT REPRESENTS A DRUG-FREE BIOENGINEERING APPROACH INTENDED TO REACH THE HUMAN TESTING PHASE (I.E., IDE MILESTONE FOR MEDICAL DEVICES) MUCH FASTER AND AT A LOWER COST THAN CONVENTIONAL DEVELOPMENT PROGRAMS FOCUSING ON PHARMACOLOGICALLY ACTIVE AGENTS. FOR THIS STUDY, IT IS HYPOTHESIZED THAT DEVELOPMENT OF A MULTIPURPOSE DEVICE ENABLES WOMEN TO ACCURATELY DEPOSIT A SMALL DOSE OF A FABRIC-LIKE, POLYMERIC SMART FIBER MATS INTRAVAGINALLY AND, SIMULTANEOUSLY, ADMINISTER SUPPLEMENTAL FLUID TO ACCELERATE RECONSTITUTION OF A BIORE- SPONSIVE, ACID-BUFFERING, AND MUCOADHESIVE SMART GEL PHASE THAT FORTIFIES THE NATURAL CONTRACEPTIVE PHYSICAL AND CHEMICAL BARRIER PROPERTIES AT THE CERVICOVAGINAL JUNCTION. IN AIM #1, WE WILL DESIGN A DUAL-COMPARTMENT DEVICE FOR FEMALE-CONTROLLED INTRAVAGINAL ADMINISTRATION OF CONTRACEPTIVE SMART FIBER MATS AND FABRICATE PROTO- TYPE DEVICES FOR IN VITRO TESTING OF CRITICAL DEVICE PERFORMANCE CHARACTERISTICS. IN AIM #2, WE WILL CONDUCT BENCH TESTING OF DUAL-COMPARTMENT DEVICE PROTOTYPES IN VITRO TO EVALUATE FIBER INSERTION AND SMART GEL FORMATION. IN AIM #3, WE WILL SOLICIT FEEDBACK FROM WOMEN ON ACCEPTABILITY AND END USER DESIRABILITY OF DIFFERENT PROTOTYPE DEVICES USING FOCUS GROUP DISCUSSIONS TO DEFINE HUMAN FACTORS CONTRIBUTING TO USE-RELATED SAFETY AND EFFICACY RISKS OF THE MULTIPURPOSE DEVICE DESIGNED FOR FEMALE-INITIATED VAGINAL DELIVERY OF CONTRACEPTIVE SMART FIBER MATS. FINALLY, WE WILL ASSESS PERFORMANCE, SAFETY, AND EFFICACY OF THE OPTIMIZED MULTIPURPOSE DEVICE FOR VAGINAL DELIVERY OF CONTRACEPTIVE SMART FIBER MATS IN VIVO USING THE SHEEP MODEL (SPECIFIC AIM #4).

INVESTIGATION AND TARGETING OF ALTERNATE BINDING SITE IN ERR? - ABSTRACT THE WORLD HEALTH ORGANIZATION ANNOUNCED A MARKED INCREASE IN PATIENTS WITH DIABETES; FROM 108 MILLION IN 1980 TO 422 MILLION IN 2014. DIABETES CAUSES SEVERE COMPLICATIONS INCLUDING BLINDNESS, HEART ATTACKS AND LOWER LIMB AMPUTATION WITH AN ESTIMATED 1.5 MILLION DEATHS ANNUALLY CAUSED BY DIABETES. THEREFORE, THERE IS GROWING INTEREST IN IDENTIFYING NOVEL DRUG TARGETS AND ALTERNATIVE THERAPEUTICS APPROACHES. ESTROGEN-RELATED RECEPTOR A (ERRA) IS A NUCLEAR HORMONE RECEPTOR THAT REGULATE GENE EXPRESSIONS RELATED TO ANTI-INFLAMMATORY ACTIVITIES, OXIDATIVE PHOSPHORYLATION, BIOGENESIS AND FATTY ACID METABOLISM. LARGE BODY OF DATA SUGGEST ERRA AS A PROMISING THERAPEUTIC TARGET IN TREATING METABOLIC DISORDERS, SUCH AS TYPE 2 DIABETES AND METABOLIC SYNDROME. THE IDENTIFICATION OF ERRA SELECTIVE SMALL MOLECULE AGONISTS WOULD BE VALUABLE CHEMICAL PROBES AND PHARMACOLOGICAL TOOLS TO FURTHER EXPLORE THE ROLE OF ERRA IN DIABETES. HOWEVER, EXISTING ERRA AGONISTS LACK IN VIVO POTENCY AND SELECTIVITY THAT ARE REQUIRED FOR THEIR USE AS CHEMICAL PROBES. IN ADDITION, THERE ARE NO X-RAY CRYSTAL STRUCTURES AVAILABLE FOR ERRA BOUND AGONISTS, WHICH HINDERED THE DISCOVERY OF SPECIFIC ERRA AGONISTS. UNDERSTANDING THE MOLECULAR BASIS OF AGONIST LIGAND BINDING TO ERRA IS CRUCIAL FOR IDENTIFICATION AND OPTIMIZATION OF NOVEL POTENT AND SPECIFIC AGONISTS. INITIAL PRELIMINARY STUDIES USING MOLECULAR DYNAMICS SIMULATIONS, REVEALED THE PRESENCE OF NOVEL ALTERNATE BINDING SITE IN ERRA. TARGETING THIS ALTERNATE SITE HOLDS PREMISE FOR DISCOVERY OF NOVEL ERRA AGONISTS. WE PROPOSE TWO SPECIFIC AIMS TO BE DONE IN TWO PHASES: 1) INVESTIGATION OF THE MECHANISM OF AGONIST LIGAND BINDING TO ERRA ORTHOSTERIC AND ALLOSTERIC SITES USING A COMBINATION OF COMPUTATIONAL AND EXPERIMENTAL APPROACHES. THIS STEP IS ESSENTIAL TO CHARACTERIZE LOW ENERGY STATE STRUCTURAL ENSEMBLES FAVOURING AGONIST BINDING TO ERRA. 2) IMPLEMENTATION OF COMPUTER-BASED DRUG DESIGN APPROACHES SUCH AS STRUCTURE-BASED VIRTUAL SCREENING FOR DISCOVERY OF NEW MOLECULAR SCAFFOLDS THAT BIND AND SELECTIVELY ACTIVATE ERRA. THESE AIMS WILL PROVIDE NOVEL, FIRST IN CLASS LIGANDS THAT SELECTIVELY ACTIVATE ERRA AND CAN BE USED AS CHEMICAL PROBES FOR INVESTIGATION OF THEIR ROLE IN DIABETES IN FUTURE GRANT PROPOSALS.

SMART POLYMER FIBERS FOR TAMPON-LIKE NONSTEROIDAL CONTRACEPTIVE DEVICES

HEART AND VASCULAR RESPONSES ACROSS THE LIFESPAN IN TS65DN MICE, A MODEL OF DOWN SYNDROME

MULTIPURPOSE DEVICE FOR FEMALE-INITIATED NONSTEROIDAL ON-DEMAND CONTRACEPTION - PROJECT SUMMARY/ABSTRACT THE CHALLENGE OF THE FUTURE IS TO DEVELOP INNOVATIVE, FEMALE-INITIATED CONTRACEPTIVE TECHNOLOGIES THAT ARE AFFORD- ABLE, SOCIALLY ACCEPTABLE, AND PROVIDE DESIRED PROTECTION FROM UNINTENDED PREGNANCY WITHOUT EXPOSING WOMEN TO ADDITIONAL HEALTH RISKS ASSOCIATED WITH SYSTEMIC DISTRIBUTION OF CONTRACEPTIVE HORMONES. OUR PRELIMINARY DATA DEMONSTRATE DISCOVERY OF DRUG-FREE, BIORESPONSIVE POLYMER COMPOSITIONS THAT DRAMATICALLY INCREASE IN VISCOSITY UPON EXPOSURE TO SEMEN, THEREBY EFFECTIVELY PREVENTING PREGNANCY IN VIVO. IN AN EXPANSION OF THIS PIONEERING SMART (= SYSTEM MUTE UNTIL ACTIVATION BY A REMOTE TRIGGER) POLYMER CONCEPT, WE PROPOSE A NOVEL DELIVERY TECHNOLOGY USING AN ON-DEMAND DUAL-COMPARTMENT VAGINAL DEVICE THAT ENABLES WOMEN TO FORTIFY THE NAT- URAL CONTRACEPTIVE BARRIERS AT THE CERVICOVAGINAL JUNCTION WITHOUT PHARMACOLOGICAL ACTION OF DRUG MOLE- CULES. THIS HIGH-RISK/HIGH-REWARD RESEARCH STRATEGY IS FUNDAMENTALLY DIFFERENT FROM CONVENTIONAL NONSTEROIDAL CONTRACEPTIVE METHODS AS IT REPRESENTS A DRUG-FREE BIOENGINEERING APPROACH INTENDED TO REACH THE HUMAN TESTING PHASE (I.E., IDE MILESTONE FOR MEDICAL DEVICES) MUCH FASTER AND AT A LOWER COST THAN CONVENTIONAL DEVELOPMENT PROGRAMS FOCUSING ON PHARMACOLOGICALLY ACTIVE AGENTS. FOR THIS STUDY, IT IS HYPOTHESIZED THAT DEVELOPMENT OF A MULTIPURPOSE DEVICE ENABLES WOMEN TO ACCURATELY DEPOSIT A SMALL DOSE OF A FABRIC-LIKE, POLYMERIC SMART FIBER MATS INTRAVAGINALLY AND, SIMULTANEOUSLY, ADMINISTER SUPPLEMENTAL FLUID TO ACCELERATE RECONSTITUTION OF A BIORE- SPONSIVE, ACID-BUFFERING, AND MUCOADHESIVE SMART GEL PHASE THAT FORTIFIES THE NATURAL CONTRACEPTIVE PHYSICAL AND CHEMICAL BARRIER PROPERTIES AT THE CERVICOVAGINAL JUNCTION. IN AIM #1, WE WILL DESIGN A DUAL-COMPARTMENT DEVICE FOR FEMALE-CONTROLLED INTRAVAGINAL ADMINISTRATION OF CONTRACEPTIVE SMART FIBER MATS AND FABRICATE PROTO- TYPE DEVICES FOR IN VITRO TESTING OF CRITICAL DEVICE PERFORMANCE CHARACTERISTICS. IN AIM #2, WE WILL CONDUCT BENCH TESTING OF DUAL-COMPARTMENT DEVICE PROTOTYPES IN VITRO TO EVALUATE FIBER INSERTION AND SMART GEL FORMATION. IN AIM #3, WE WILL SOLICIT FEEDBACK FROM WOMEN ON ACCEPTABILITY AND END USER DESIRABILITY OF DIFFERENT PROTOTYPE DEVICES USING FOCUS GROUP DISCUSSIONS TO DEFINE HUMAN FACTORS CONTRIBUTING TO USE-RELATED SAFETY AND EFFICACY RISKS OF THE MULTIPURPOSE DEVICE DESIGNED FOR FEMALE-INITIATED VAGINAL DELIVERY OF CONTRACEPTIVE SMART FIBER MATS. FINALLY, WE WILL ASSESS PERFORMANCE, SAFETY, AND EFFICACY OF THE OPTIMIZED MULTIPURPOSE DEVICE FOR VAGINAL DELIVERY OF CONTRACEPTIVE SMART FIBER MATS IN VIVO USING THE SHEEP MODEL (SPECIFIC AIM #4).

IRON METABOLISM IN TS65DN MICE, A MODEL OF DOWN SYNDROME - PROJECT SUMMARY/ABSTRACT DOWN SYNDROME (DS) IS A DEVELOPMENTAL DISABILITY THAT TYPICALLY RESULTS FROM THE TRIPLICATION OF CHROMOSOME 21 WITH AN OCCURRENCE OF 1 IN 700 LIVE BIRTHS. CHROMOSOME 21 TRIPLICATION MAY ALTER NORMAL GENE EXPRESSION AND LEAD TO INTELLECTUAL DISABILITY, EARLY ONSET ALZHEIMER’S DISEASE, CONGENITAL HEART DISEASE, HEMATOLOGIC DISORDERS, AMONG OTHER CONDITIONS. DYSREGULATION OF IRON HOMEOSTATIC MECHANISMS MAY BE AN UNDERLYING FACTOR IN CLINICAL OUTCOMES ASSOCIATED WITH DS. IRON IS A TRACE ELEMENT WELL-KNOWN FOR ITS INVOLVEMENT WITH PHYSIOLOGICAL PROCESSES THAT INCLUDE OXYGEN TRANSPORT, INFLAMMATORY RESPONSE, ENERGY METABOLISM, AND DNA SYNTHESIS. IRON HOMEOSTATIC DYSREGULATION IN DS COULD LEAD TO COMPROMISED PLASMA IRON LEVELS AND TISSUE IRON ACCUMULATION THAT CATALYZES THE PRODUCTION OF REACTIVE OXYGEN RADICAL SPECIES (ROS). DESPITE REPORTS OF IRON STATUS PARAMETERS IN DS THERE IS A LACK OF CLEAR AND COMPREHENSIVE UNDERSTANDING OF IRON HOMEOSTATIC REGULATION AMONG THIS POPULATION OF INDIVIDUALS. THE TS65DN MOUSE IS AN ESTABLISHED MODEL OF DS THAT MAY HOLD CONSIDERABLE VALUE TO STUDY MECHANISTIC FACTORS THAT REGULATE IRON HOMEOSTASIS IN DS. THE OBJECTIVE OF THIS PROJECT IS TO DELINEATE SEX AND AGE-RELATED ALTERATIONS IN IRON HOMEOSTATIC REGULATION OVER THE ADULT LIFESPAN OF TS65DN MICE AND TO ASSOCIATE CHANGES IN IRON REGULATION WITH TISSUE IRON LEVELS AND OXIDATIVE STRESS. IN THESE STUDIES, TISSUES (BRAIN, LIVER, AND PLASMA) FROM TS65DN MICE AND WILD-TYPE (WT) COLONY CONTROLS AT 3, 12, AND 18 MONTHS OF AGE WILL BE STUDIED TO ADDRESS TWO INTEGRATED SPECIFIC AIMS: 1) DEPICT THE IRON HOMEOSTATIC PHENOTYPE OF TS65DN MICE ACROSS THE ADULT LIFESPAN, AND 2) DETERMINE THE IMPACT OF HYPOXIA EXPOSURE (10% INSPIRED O2) ON SYSTEMIC AND TISSUE IRON HOMEOSTASIS, HEMATOLOGIC PROFILE, AND TISSUE OXIDATIVE STRESS IN TS65DN MICE. THE FIRST AIM OF THIS PROPOSAL WILL ESTABLISH THE UTILITY OF THE TS65DN MOUSE MODEL TO STUDY IRON STATUS AND IRON HOMEOSTATIC REGULATION IN DS. IT IS HYPOTHESIZED THAT TS65DN MICE WILL SHOW GREATER INFLAMMATION THAT WILL PROMOTE AN IRON REGULATION RESPONSE LEADING TO LOWER PLASMA COMPARTMENT IRON AND ELEVATED IRON IN THE STORAGE COMPARTMENT. ELEVATED TISSUE IRON IN TS65DN MICE IS POSTULATED TO ASSOCIATE WITH GREATER OXIDATIVE INJURY. THE SECOND AIM WILL EMPLOY HYPOXIA EXPOSURE TO ALTER IRON HOMEOSTATIC REGULATION OF TS65DN AND WT MICE TO TEST THE HYPOTHESIS THAT HYPOXIA INDUCED IRON DISTRIBUTION SHIFTS FROM STORAGE TO THE PLASMA COMPARTMENT WILL REDUCE TS65DN TISSUE IRON TOXICITY AND IMPROVE THE HEMATOLOGIC PROFILE. FURTHERMORE, IT IS HYPOTHESIZED THAT MALE MICE WILL DISPLAY GREATER IRON STATUS AND OXIDATIVE STRESS THAN FEMALES, WITH TS65DN SHOWING GREATER LEVELS THAN WT CONTROLS. AS IRON METABOLISM DYSREGULATION AND TISSUE IRON ACCUMULATION CAN BECOME MORE PROMINENT WITH AGING, UNDERSTANDING IRON METABOLISM IN DS IS OF UTMOST IMPORTANCE AS LIFE EXPECTANCY OF THIS POPULATION HAS DRAMATICALLY IMPROVED OVER THE PAST SEVERAL DECADES.

RAPID AND SENSITIVE IN VIVO DETECTION OF OPIOID PEPTIDES

PHARMACOLOGICAL PROBES BASED ON MITRAGYNINE PSEUDOINDOXYL

DEVELOPMENT OF NOVEL ERRA SELECTIVE AGONISTS AS CHEMICAL PROBES FOR THE POTENTIAL TREATMENT OF ALZHEIMER'S DISEASE

THE ROLE OF INOSITOL POLYPHOSPHATE 4 PHOSPHATASE IN PLATELET FUNCTIONS

TARGETING REV-ERB REGULATION OF MITOCHONDRIA AS A THERAPEUTIC STRATEGY IN ALZHEIMER'S DISEASE

HPSL - PHARMACY - PD CHANGES

CLOSEOUT DOCUMENT NUMBER