THIS PROPOSAL RESPONDS TO THE MDIP RESEARCH AREA ENTITLED "SAFE DRUG REGIMENS TO REDUCE THE MORTALITY AND MORBIDITY OF BACTERIAL AND MYCOTIC INFECTIONS, PARTICULARLY HOSPITAL ASSOCIATED INFECTIONS" AS CITED IN THE DHHS OMNIBUS SOLICITATION.

THIS PROPOSAL RESPONDS TO THE MDIP RESEARCH AREA ENTITLED "SAFE DRUG REGIMENS TO REDUCE THE MORTALITY AND MORBIDITY OF BACTERIAL AND MYCOTIC INFECTIONS, PARTICULARLY HOSPITAL ASSOCIATED INFECTIONS" AS CITED IN THE DHHS OMNIBUS SOLICITATION. PREVIOUS STUDIES HAVE SHOWN PREGELANTINIZED STARCH TO BE EFFECTIVE IN THE SYMPTOMATIC TREATMENT OF COMMON DIARRHEA IN NEONATAL CALVES, AND SHULCON INDUSTRIES INC. NOW MARKETS A PRODUCT IN CANADA FOR THAT PURPOSE. THISPROGRAM WILL EXTEND THE ANTIDIARRHEAL APPLICATION OF PREGELANTINIZED STARCH TO A SECOND, MONOGASTRIC, ANIMAL SPECIES LEADING TO THE DEVELOPMENT OF AN ANTIDIARRHEAL DRUG APPLICABLE TO HUMAN INFANTS. THE PHASE I PROGRAM WILL ESTABLISH THE EFFICACY OF PREGELATINIZED STARCH IN TREATING SPECIFIC ACUTE NEONATAL PIG DIARRHEA AS A MODEL FOR THE HUMAN INFANTILE DISEASE. SELECTED STRAINS OF ENTEROTOXIGENIC "E. COLI" WITH DIFFERENING PILUS ANTIGENS WILL BE EMPLOYED INDEPENDENTLY TO CHALLENGE NEWBORN PIGS FROM NON-IMMUNIZED GILTS TO PRODUCT DIARRHEAL DISEASE. DIARRHEIC PIGS WILL BE ASSIGNED RANDOMLY TO TREATMENT OR PLACEBO GROUPS IN A DOUBLE BLIND DESIGN, TREATED ACCORDINGLYAND OBSERVED FOR UP TO SEVEN DAYS. FORM OF STOOL AND AND FREQUENCY OF DEFECATION WILL BE MONITORED TO ESTABLISH THE DURATION OF DIARRHEA. BODY WEIGHT AND CLINICAL HYDRATION STATE WILL BE DETERMINED DAILY AS INDEPENDENT MEASURES OF THE EFFECT OF THE THERAPEUTIC METHOD. RANDOMLY SELECTED PIGS WILL BE SACRIFICED ONE DAY AFTER COMPLETION OF THE THERAPEUTIC SERIES AND THE SIZES OF THE POPULATIONS OF THE CHALLENGE STRAIN ADHERING TO THE INTESTINAL MUCOSA WILL BE DETERMINED. HISTOCHEMICAL EXAMINATION OF SECTIONS FROM SEGMENTS OF THE SMALL INTESTINE WILL EVALUATE THE PASSAGE AND LOCUS OF STARCH THROUGHOUT THAT ORGAN. NECROPSIES WILL BE PERFORMED ON ALL PIGS THAT DIE DURING THESTUDY. THE OUTPUT OF THE STUDY WILL BE A MEASURE OF THE EFFECTIVENESS OF PREGELATINIZED STARCH IN ARRESTING SPECIFICACUTE DIARRHEA OF NEONATAL PIGS DUE TO SEVERAL PILIATED TYPES OF "E.COLI" AND WILL DETERMINE THE APPROPRIATENESS OF PROCEEDING TO MORE COMPLETE PRE-CLINICAL STUDIES TO ESTABLISH MECHANISTICS AND ANIMAL SAFETY PRIOR TO PHASE I CLINICAL STUDIES IN HUMANS.