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  • 1
    ISSN: 1573-904X
    Schlagwort(e): peptidomimetic stability ; alkoxycarbonylamidine ; ester ; prodrug ; pH-rate profile ; GPIIbIIIa
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Alkoxycarbonylamidine prodrug modification was used to mask the positively-charged amidine moiety of an Arg-Gly-Asp pepti-domimetic and enhance oral bioavailability. The aqueous stability of ethoxycarbonylamidine (EGA), ethanethiocarbonylamidine (ETCA) and phenoxycarbonylamidine (PCA) prodrugs was examined. Methods. Degradation was followed by RP-HPLC and rate constants were determined from a degradation scheme defined by product analysis. Results. EGA gave a pH of maximum stability at pH ∼7 and was independent of pH below pH ∼4. A novel degradation pathway of EGA, conversion to ethoxycarbonyl- aminocarbonyl, was observed below pH 7. The relative rates below pH 7 were ECA~ETCA〈PCA, in the same order of decreasing pKa of the conjugate acid of the substituted amidino group. Base-catalyzed cleavage of EGA to yield the amidine derivative gave the relative rates ECA〈ETCA〈PCA, in agreement with the decreasing pKa of the leaving groups. Conclusions. The observed rate constants at all pHs were small enough that only 5-30% (depending on the substituent) undesirable degradation is predicted during transit time of the gut. The spontaneous post-absorptive conversion to the amidine drugs at neutral pH is predicted to be 6x greater for the PCA than the EGA prodrugs.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    ISSN: 1573-7225
    Schlagwort(e): Adenoma ; amines ; colon ; meat-products ; mutagens ; United States
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The often observed association between red meat and colorectal cancercould be due in part to mutagens, such as heterocyclic amines (HCA), that arepresent in cooked meat. HCAs are highly mutagenic and cause intestinal tumorsin animals. The hypothesis that HCAs are also carcinogenic to humans remainsto be substantiated in epidemiologic studies. We determined the associationsof meat preparation and frequency of intake (proxy variables for HCAexposure, since HCA concentration depends on the type of meat and the way itis cooked) with the prevalence of distal colorectal adenomas in asigmoidoscopy-based case-control study of 488 matched pairs of subjects fromtwo California (United States) Kaiser Permanente Medical Centers. A more thantwofold difference in adenoma prevalence between subjects at extreme ends ofestimated HCA intake was observed. For subjects who ate red meat more thanonce per week, fried it more than 10 percent of the time, and ate it with adarkly browned surface, compared with subjects who ate red meat one time orless per week, fried it 10 or less percent of the time, and ate it with alightly browned surface, the odds ratio was 2.2 (95 percent confidenceinterval = 1.1-4.3). Adenoma prevalence also increased with frequency offrying red meat (P trend = 0.004). These results are consistent with acarcinogenic effect of HCA.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Digestive diseases and sciences 13 (1968), S. 21-34 
    ISSN: 1573-2568
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Conclusion Insulin gastric analysis, properly performed and interpreted, is a reliable indicator of postoperative clinical status of patients with peptic ulcer. It can be used to assess the adequacy of vagotomy or antrectomy. Clinical experience with insulin gastric analysis confirms the findings of animal studies which indicate that cephalic secretion is essentially an integrated neurohumoral response, involving a vagal release of antral gastrin. The profound depression of basal acid in the negative-response group also indicates that basal secretion is largely under cephalic control.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Digestive diseases and sciences 13 (1968), S. 643-655 
    ISSN: 1573-2568
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Conclusion With rare exception, the tolbutamide gastric analysis has been shown to be a reliable indicator of clinical status in postsurgical peptic ulcer patients. In this group the side effects were rare and, when present, were very mild. Bad risk patients, considered unacceptable for an insulin gastric analysis, tolerated the entire tolbutamide test procedure without any ill effects. Only one serious reaction was observed in a patient in whom unexpected fasting hypoglycemia was overlooked. Our experience strongly suggests that tolbutamide is a useful supplementary test for evaluating the adequacy of vagotomy and/or antrectomy. In poor risk patients and the aged, the tolbutamide test is the procedure of choice.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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