| 5. |
- Lundin, Stefan, et al.
(författare)
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Pharmacokinetic and pharmacologic properties of antiuterotonic oxytocin analogs in the rat
- 1993
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - 1521-0103. ; 264:2, s. 783-788
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacologic and pharmacokinetic properties were evaluated in a series of antiuterotonic oxytocin analogs, modified at positions 1, 2, 4, 8 and, in one case, position 9 of the oxytocin (OT) molecule. [Mpa1,D-Tyr2(Et),Val4,Orn8,desGly9]-OT, [Mpa1,Tyr2(Et),Val4,Orn8]-OT and [Mpa1,D-Tyr2,Val4,Orn8]-OT displayed similar plasma clearance rates (Clps) using the constant infusion method in rats. Two analogs, [Mpa1,D-Tyr2(Et),Val4,Orn8]-OT and, particularly, [Mpa1,D-Tyr2(Et),Thr4,Orn8]-OT, were cleared at significantly higher rates compared with the others. [Mpa1, D-Tyr2(Et), Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT were most potent in eliciting a short-term in vivo antiuterotonic effect, whereas the duration of effect was longest for [Mpa1, D-Tyr2, Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT. The Clp of [Mpa1, D-Tyr2, Val4, Orn8]-OT was similar regardless of the infusion rate. No relationship between antiuterotonic effect and Clp of the five peptides could be demonstrated, and no significant linear correlation between Clp and effect duration was found. The apparent volumes of distribution for the present analogs were 10-fold larger than the blood volume, a finding to be considered when measuring in vivo antagonistic activity. The 24-h urinary excretion ranged from 14.3 to 25.6% of the i.v. dose and was negatively correlated with peptide lipophilicity. It is concluded that, in addition to diverging pharmacologic properties, peptide analogs may differ markedly in kinetic parameters like Clp, volumes of distribution and urinary excretion despite minor molecular modifications.
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| 6. |
- Sjöström, Lars, et al.
(författare)
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Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state
- 1992
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Ingår i: International Journal of Obesity. ; 19, s. 465-479
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Tidskriftsartikel (refereegranskat)abstract
- Department of Medicine, Sahlgren's Hospital, University of Göteborg, Sweden. SOS (Swedish obese subjects) is an on-going intervention trial designed to determine whether the mortality and morbidity rates among obese individuals who lose weight by surgical means (gastric banding, vertical banded gastroplasty and gastric by-pass) differ from the rates associated with conventional treatment. For this purpose, the study is recruiting a sample of obese men and women who constitute a registry of potential subjects from which the participants are drawn. Eligibility criteria for participation in the registry were: age at application 37-57 years and BMI greater than or equal to 34 kg/m2 for men and greater than or equal to 38 kg/m2 for women. Before receiving a health examination, all patients complete extensive questionnaires on current and past health status, utilization of medical care and medications, socio-economic status, psychological profiles, dietary habits, physical activity, weight history, and familial disposition to obesity. Each surgical case is matched to its optimal control in the registry, to ensure that the two groups do not differ systematically with respect to any of 18 matching variables that may affect prognosis. The first 1006 subjects included in the registry have been studied with respect to morbidity and compared with on-going population studies of men and women in Göteborg, Sweden. The relative risks of prevalent disease and symptoms associated with obesity in 50-year-old males and females respectively were 4.3 and 4.7 (dyspnoea), 14.7 and 11.8 (angina), 6.3 (myocardial infarction, males only), 2.1 and 4.5 (hypertension), 5.2 and 6.6 (diabetes), 4.6 and 26.1 (claudication) and 1.7 and 1.8 (gall bladder disease). Correspondingly, obese males and females display elevations of systolic and diastolic blood pressure, fasting glucose, insulin, triglyceride, and uric acid levels. However, total cholesterol was not increased in obese males and was in fact significantly lower in obese compared with reference women. HDL-cholesterol was lower in obese than reference men (data were not available in reference women). The rate of taking sick pensions was over twice as high in SOS obese patients than in population controls. Finally, comparison of measurements with self-reported prevalence estimates revealed a considerable amount of previously undiagnosed hypertension and diabetes in the obese subjects. These data suggest that the excess health risks associated with obesity may not be fully appreciated. PMID: 1322873 [PubMed - indexed for MEDLINE]
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