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C A D'Ambrosio

Publications and source records attributed to C A D'Ambrosio.

3 recordsLinked to original sources
PubMed1993

Conformational mobility in cyclic oligopeptides.

Analysis of two isomeric cyclic hexapeptides of composition (Asp, Arg, Gly2, Pro, D-Pro) by a nuclear Overhauser effect constrained distance geometry conformation search yielded a narrowly defined backbone conformation for one and considerable ambiguity about the conformation in part of the other. Preliminary 13C relaxation studies of these peptides suggest that it is possible that this difference may correspond to a physical difference in internal mobility. In connection with this observation, other experimental evidence bearing on the backbone conformational mobility of cyclic oligopeptides with 4-10 residues, frequently considered to have well-defined backbones, is reviewed. Conformational heterogeneity involving rotation of a peptide bond plane relative to the overall ring plane is identified as a common phenomenon. Nuclear magnetic resonance line-shape studies at temperatures down to 200 K can detect backbone motions with activation free energy barriers down to about 10 kcal/mole, but conformational exchange with lower barriers, though detectable in other ways, will not be obvious from nmr spectra alone.

Amino Acid Sequence↗
PubMed1993

Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.

OBJECTIVES: To determine whether a continuous i.v. infusion of cimetidine, a histamine-2 (H2) receptor antagonist, is needed to prevent upper gastrointestinal (GI) hemorrhage when compared with placebo and if that usage is associated with an increased risk of nosocomial pneumonia. Due to the importance of this latter issue, data were collected to examine the occurrence rate of nosocomial pneumonia under the conditions of this study. DESIGN: A multicenter, double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomized to receive cimetidine (n = 65) as an iv infusion of 50 to 100 mg/hr or placebo (n = 66). SETTING: Intensive care units in 20 institutions. PATIENTS: Critically ill patients (n = 131), all of whom had at least one acute stress condition that previously had been associated with the development of upper GI hemorrhage. MEASUREMENTS AND MAIN RESULTS: Samples of gastric fluid from nasogastric aspirates were collected every 2 hrs for measurement of pH and were examined for the presence of blood. Upper GI hemorrhage was defined as bright red blood or persistent (continuing for > 8 hrs) "coffee ground material" in the nasogastric aspirate. Baseline chest radiographs were performed and sputum specimens were collected from all patients, and those patients without clear signs of pneumonia (positive chest radiograph, positive cough, fever) at baseline were followed prospectively for the development of pneumonia while receiving the study medication. Cimetidine-infused patients experienced significantly (p = .009) less upper GI hemorrhage than placebo-infused patients: nine (14%) of 65 cimetidine vs. 22 (33%) of 66 placebo patients. Cimetidine patients demonstrated significantly (p = .0001) higher mean intragastric pH (5.7 vs. 3.9), and had intragastric pH values at > 4.0 for a significantly (p = .0001) higher mean percentage of time (82% vs. 41%) than placebo patients. Differences in pH variables were not found between patients who had upper GI hemorrhage and those patients who did not, although there was no patient in the cimetidine group who bled with a pH < 3.5 compared with 11 such patients in the placebo group. Also, the upper GI hemorrhage rate in patients with one risk factor (23%) was similar to that rate in patients with two or more risk factors (25%). Of the 56 cimetidine-infused patients and 61 placebo-infused patients who did not have pneumonia at baseline, no cimetidine-infused patient developed pneumonia while four (7%) placebo-infused patients developed pneumonia. CONCLUSIONS: The continuous i.v. infusion of cimetidine was highly effective in controlling intragastric pH and in preventing stress-related upper GI hemorrhage in critically ill patients without increasing their risk of developing nosocomial pneumonia. While the number of risk factors and intragastric pH may have pathogenic importance in the development of upper GI hemorrhage, neither the risk factors nor the intragastric pH was predictive. Therefore, short-term administration of continuously infused cimetidine offers benefits in patients who have sustained major surgery, trauma, burns, hypotension, sepsis, or single organ failure.

Adolescent↗
PubMed1992

Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides.

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.

Amino Acid Sequence↗