The Synthesis and Reactions of 7-Carboxy Isatoic Anhydride

This 16 page thesis examines the preparation and characterization of 7-carboxy isatoic anhydride and the study of the reactions of this compound of new composition

Monitoring Physiological Variables with Membrane Probes

This project has demonstrated the possibility of using membrane probes in rodents to monitor physiological variables for extended periods of time. The utility of these probes in physiological studies of microgravity has been demonstrated. The feasibility of developing on-line sensors has also been demonstrated and allows for the possibility of developing real-time automated monitoring systems which can be used in ground-base physiological research as well as in research and medical monitoring in space. In addition to space applications these techniques can be extended to medical monitoring in critical care situations on earth as well as facilitating research in many human and animal diseases

Development of an On-animal Separation-based Sensor for Monitoring Drug Metabolism in Freely Roaming Sheep

The development of an on-animal separation-based sensor that can be employed for monitoring drug metabolism in a freely roaming sheep is described. The system consists of microdialysis sampling coupled directly to microchip electrophoresis with electrochemical detection (MD-ME-EC). Separations were accomplished using an all-glass chip with integrated platinum working and reference electrodes. Discrete samples from the microdialysis flow were introduced into the electrophoresis chip using a flow-gated injection approach. Electrochemical detection was accomplished in-channel using a two-electrode isolated potentiostat. Nitrite was separated by microchip electrophoresis using reverse polarity and a run buffer consisting of 50 mM phosphate at pH 7.4. The entire system was under telemetry control. The system was first tested with rats to monitor the production of nitrite following introduction of nitroglycerin into the subdermal tissue using a linear probe. The data acquired using the on-line MD-ME-EC system was compared to that obtained off-line analysis by liquid chromatography with electrochemical detection (LC-EC), using a second microdialysis probe implanted parallel to the first probe in the same animal. The MD-ME-EC device was then used on-animal to monitor the subdermal metabolism of nitroglycerin in sheep. The ultimate goal is to use this device to simultaneously monitor drug metabolism and behavior in a freely roaming animal

Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment

While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as limited knowledge regarding their bioavailability, metabolism and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer’s disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric (Po) forms. In this study we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of ~400 nM. Most importantly we report for the first time that a biosynthetic epicatechin metabolite, 3’-O-methyl-epicatechin-5-O-β-glucuronide (3’-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3’-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in Alzheimer’s disease and other forms of dementia

EXPERIMENTAL DIABETES IN DOGS. I: EFFECTS OF PANCREATIC TISSUE IMPLANTS. II: PLASMA OSMOLALITY FOLLOWING GLUCOSE INFUSION

Abstract not availabl

Continuous Flow through Peritoneal Dialysis (Cfpd): Comparison of Efficiency to Ipd, Tpd, and Capd in An Animal Model

Objective To determine whether continuous flow through peritoneal dialysis (CFPD), a treatment schedule in which peritoneal dialysate is infused continuously into one part of the abdomen (over the liver) and is drained from a distant part of the abdomen (the pelvis), can provide greater clearance than continuous ambulatory peritoneal dialysis (CAPD), tidal peritoneal dialysis (TPD), or intermittent peritoneal dialysis (IPD). Design A prospective study comparing four schedules of peritoneal dialysis in the awake, normal dog, using glucose clearance as a substitute for urea clearance. Methods We placed two chronic dialysis catheters into the abdomen of anesthetized dogs (with intraperitoneal portions of fluted or miniature column-disc design). On successive days, with the dogs awake and prone, we performed peritoneal dialysis for 4 hours with 1.5% dialysate according to one of four schedules, each with 2 L maximum intraperitoneal volume: CFPD (unidirectional flow at an average of 3.6 L/hr), IPD (2 L/hr), TPD (average of 3.6 L/hr, 1 L residual volume), and CAPD (2 L/4 hr). Glucose and urea clearances were calculated from blood and peritoneal concentrations and dialysate flow rates. Results Stabilized glucose clearances (from 60 to 240 minutes) averaged 11 ± 5 mL/min for IPD, TPD, and CFPD, and 5 ±2 mU minfor CAPD. However, glucose clearances of CFPD were 13 ± 6 mL/min when the intraperitoneal volume was maintained at 800 -1000 mL, and 16.5 ± 6 mL/min when flow rate was 6 L/hr. Urea clearances were twice the measured glucose clearances. Conclusion When CFPD is performed with an appropriate intraperitoneal volume and flow, it is the most chemically effective method of peritoneal dialysis in removing small molecules like urea. </jats:sec

Postprandial Glycemic and Insulinemic Responses to Common Breakfast Beverages Consumed with a Standard Meal in Adults Who Are Overweight and Obese

Breakfast beverages with different nutrient compositions may affect postprandial glycemic control differently. We assessed the effects of consuming (1) common breakfast beverages (water, sugar-sweetened coffee, reduced-energy orange juice (OJ), and low-fat milk (LFM)); and (2) fat-free, low-fat, and whole milk with breakfast on postprandial plasma glucose and insulin responses in adults who were overweight/obese. Forty-six subjects (33F/13M, body mass index: 32.5 ± 0.7 kg/m2, age: 50 ± 1 years, mean ± SEMs) consumed a standard sandwich with one of the six beverages on separate mornings in randomized order. The test beverages (except water) each contained 12 g digestible carbohydrate. Plasma glucose and insulin concentrations were measured from blood obtained pre- and post-meal at 30-min intervals for 4 h and incremental areas under the curve (AUC) were computed. We found (1) among different beverage types, glucose AUC was higher for coffee versus water, OJ, and LFM. Insulin AUC was higher for coffee and LFM versus OJ and water; (2) Glucose AUCs were not different among water and milks while insulin AUC was higher for milks versus water. In conclusion, consumption of water, reduced-energy OJ, or milk (irrespective of fat content) with a meal may be preferable to consuming sugar-sweetened coffee for glucose control in middle-aged adults who are overweight and obese