Ralph Didlake

Attenuation of ischemic renal injury with fructose 1,6-diphosphate

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

Experimental small bowel transplantation utilizing cyclosporine.

Cyclosporine prolonged the survival of ectopic smallbowel allografts in a canine model. A 9-fold increase inmean survival as compared with controls was obtained. Addition of prednisone to cyclosporine did not result infurther graft prolongation, but improved the gross and histological appearance of the allograft. Monitoring the motility and histology of the allograft appears to beautiful in predicting approaching rejection. Xylose absorption was not helpful in this regard. A new technique for measuring fat absorption in the transplant is described. Following allografting, fat absorption is resumed by 14 days posttransplantation.

Cortisone, vitamin A, and wound healing: The importance of measuring wound surface area

Traditional methods of measuring wound strength have often ignored one of the most important variables, i.e., wound surface area. Using a readily reproducible method of determining wound surface area, the effect of topical vitamin A on steroid-treated rats was studied. Findings revealed a significant (P less than 0.001) increase in wound strength with topical vitamin A application. No difference could be detected between steroid-treated and saline-treated rats when wound surface area was taken into account. Measurement of wound surface area is essential for meaningful results in wound healing studies.

Prevention of α-naphthylthiourea-induced pulmonary edema with fructose-1,6-diphosphate

Neutrophil-derived oxygen free radicals have been implicated in the pathogenesis of noncardiogenic pulmonary edema. Fructose-1,6-diphosphate (FDP) has been shown to inhibit oxygen free radicals production by activated neutrophils. Thus, we investigated whether FDP would attenuate formation of pulmonary edema in anesthetized dogs injected with α -naphthylthiourea (ANTU). Hemodynamic studies involved measurements of left ventricular systolic and end-diasystolic pressures (LVSP and LVEDP), pulmonary artery pressure (PaP), heart rate (HR), and cardiac output (CO). Mean wet weight to dry weight ratios of lung tissue samples were calculated. Following baseline measurements, dogs were injected intravenously (IV) with ANTU 5 mg / kg (n = 16) and 10 mg / kg (n = 8) and half of the dogs were randomly selected to receive 75 mg / kg FDP (10%) and subsequent infusion of 7 mg / kg / min. The rest were given 0.9% NaCl in the same manner. Four hours after ANTU administration, the animals were euthanatized. Except for decline in the CO (nonsignificant), no significant changes in systemic hemodynamics within and between the groups were noted. In the FDP group, PaP and pulmonary arteriolar resistance (PaR) remained unchanged. In the saline group, PaP increased from 12.5 ± 2.44 to 21.8 ± 3.14 mm Hg (P <. 001) and PaR from 166 ± 29 to 468 ± 74 dynes · cm / sec 5 (P <. 005). During the study LVDEP, PaO 2, PaCO 2, and hematocrit did not change significantly within and between the groups. The lungs mean wet weight to dry weight ratios for the sham-operated dogs were 4.20 ± 0.41, for the FDP group 4.32 ± 0.59 and 6.22 ± 1.37 for the saline group (P <. 0005). These data indicate that FDP protected the lung from ANTU-induced injury.

Financial Conflicts of Interest, Disclosure, and Academic Discipline.

Peer assessments of researchers’ financial conflicts of interest (FCOIs) are crucial to effective FCOI management. We sought to determine how academics perceive FCOI disclosure and whether their perceptions vary depending on discipline and educational backgrounds. Participants (faculty and staff members from a multi-disciplinary academic medical center) responded to a questionnaire involving 10 hypothetical scenarios in which researchers either disclosed or failed to disclose a financial conflict (between-participants manipulation). Participants viewed disclosure as important and believed that researchers’ objectivity would be affected by undisclosed FCOIs. In contrast to non-physicians, physicians showed greater recognition that the existence of an FCOI does not depend on its disclosure. This suggests that physicians are relatively well informed about FCOIs, which is likely attributable to more education about them.