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E Albrecht

Publications and source records attributed to E Albrecht.

At least 37 records · Page 2Linked to original sources
PubMed1991

Gonadotropin-releasing hormone (GnRH) analogs: relationship between their structure, proteolytic inactivation and pharmacokinetics in rats.

There are two types of superactive agonists of gonadotropin-releasing hormone (GnRHa-I: (D-amino acid)6-GnRH and GnRHa-II: (D-amino acid)6-(desGly)10-GnRH- ethylamide) the high hormonal activity of which is understood to be due to their higher receptor affinity and their higher proteolytic stability as compared with the native GnRH sequence. Using the soluble fractions of various rat tissues in studies on the inactivation of GnRH peptides, we confirmed the higher proteolytic resistance of GnRHa-II, but not of D-Phe6-GnRH (GnRHa-I) and of another analog, D-Trp3-D-Phe6-GnRH, as compared with GnRH. The exact behaviour of the peptides during degradation was found to be dependent on the peptide concentrations used, showing the importance of using conditions as near to the physiological ones a possible. Towards the membrane fractions, however, the order of degradability was found to be GnRH much greater than D-Phe6-GnRH much greater than D-Trp3-D-Phe6-GnRH. The pharmacokinetic consequences of the different proteolytic degradabilities of the GnRH peptides, observed in rats, were a moderate increase in the biological half-life of D-Phe6-GnRH by 2.5-fold, as compared with GnRH, and a small increase in half-life of D-Trp3-D-Phe6-GnRH by 1.4-fold when compared with D-Phe6-GnRH. Whereas no intact GnRH was recovered in rat urine, small amounts of D-Phe6-GnRH (about 1% of dose) and high amounts of D-Trp3-D-Phe6-GnRH (25.5%) were excreted into urine. Combining the biochemical and pharmacokinetic data, it is concluded that proteolytic stability of GnRH analogs in pharmacological terms means stability towards membrane enzymes (pharmacologically-related stability) and that designing analogs with further increased proteolytic stability will be of only limited consequences with respect to their biological half-lives, the glomerular filtration rate of the kidney becoming the determining factor in the peptide clearance.

Amino Acid Sequence↗
PubMed1991

In-vivo release of a GnRH agonist from a slow-release poly(lactide-glycolide) copolymer preparation: comparison in rat, rabbit and guinea-pig.

Different batches of 50:50 poly((+-)-lactide-glycolide) copolymer (PLG) were used as biodegradable carriers for D-Phe6-gonadotropin-releasing hormone (GnRHa) in the form of injectable long-acting implants loaded with 10% GnRHa and tracer amounts of [125I]GnRHa. After their injection subcutaneously into rats, rabbits, and guinea-pigs, the release kinetics of the peptide were determined by counting the radioactivity remaining in the implants (i) after recovery from the rats after death or (ii) directly on the skin above the injection site of rabbits and guinea-pigs in-vivo. No significant differences in the release pattern of the peptide amongst the three species whether the release process was controlled by diffusion or by degradation of the polymeric matrix were found. It is concluded that the results of in-vivo release tests using laboratory animals are valid for man and that enzymes are not involved in the degradation of the polymeric matrix. The results may be of general importance for the use of long-term release PLG formulations of highly active drugs, especially peptides and proteins.

Animals↗
PubMed1985

Electroconvulsive therapy: a survey of use in the private psychiatric hospital.

All 184 member hospitals of the National Association of Private Psychiatric Hospitals (NAPPH) were sent a specially designed 19-item questionnaire regarding their use of electroconvulsive therapy (ECT). Of the 153 respondents, 89 (58%) reported using ECT. Most followed the guidelines delineated in the 1978 American Psychiatric Association Task Force Report.

Adolescent↗
PubMed1984

Medicated versus saline nose drops in the management of upper respiratory infection.

Seventy-four children from three weeks to two years of age with various upper respiratory symptoms were randomly assigned to three groups: two intervention groups (saline nose drops; medicated nose drops) and a control group (no nose drops). Forty-six children returned for check-up two days later. Subjects in all three groups improved between first and second contact. There was no significant difference between the three groups. It is concluded that medicated nose drops are not essential in the treatment of upper respiratory infection and rhinitis.

Administration, Intranasal↗
PubMed1983

Direct tritium-labelling into histidine of luteinizing hormone-releasing hormone agonists and use of the tracers in studies on proteolytic breakdown.

Analogs of luteinizing hormone-releasing hormone (LHRH) having higher biological activity than LHRH itself are being mainly used to study the biological effects and the mechanism of action of LHRH. In the present study, conditions for the direct 3H-labelling at the histidine residue of analogs of LHRH were worked out, circumventing the synthesis of precursor peptides for labelling. [D-Phe6,desGly10]-LHRH ethylamide and [D-Ser(But)6,desGly10]-LHRH ethylamide were tritiated by tritium gas and a 10% Pd/Al2O3 catalyst to high specific radioactivities. The labelled peptides are sufficiently stable to be used in biochemical studies. The degradability of the analogs by homogenates of various tissues of rats was compared with that of the native LHRH. The analogs were shown to be distinctly degradable, but to a lower extent. The kidney homogenate degrades the analogs [D-Phe6,desGly10]- and [D-Ser(But)6,desGly10]-LHRH ethylamide with 35 and 50%, respectively, of the velocity observed with LHRH, whereas the degradation velocity of the analogs by a homogenate of the hypothalamus and pituitary is only 10% of that of LHRH. It is suggested that the lower degradability of the analogs at peripheral sites and target sites (pituitary, ovary) explains partly their higher biological activity.

Animals↗
PubMed1980

Prevention of cystic ovary induction in rabbits by aminoglutethimide.

Polycystic ovaries were induced in thyroidectomized rabbits by the administration of either 25 IU human chorionic gonadotrophin or 10 IU pregnant mare serum daily for a period of 20 days. Cystic ovaries in rabbits exhibited subnormal (P < 0.01) ovarian delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) concentration and specific activity. Since weight of cystic ovaries was markedly elevated, however, total capacity for delta 4-3-ketosteroid production was enhanced. Concomitant administration of chorionic gonadotrophin and aminoglutethimide phosphate to thyroidectomized rabbits prevented the formation of cystic ovaries indicating that a steroid, or steroids formed beyond cholesterol in the biosynthesis pathway is necessary for the experimental induction of cystic ovaries in this laboratory animal.

3-Hydroxysteroid Dehydrogenases↗
PubMed1975

Calcium uptake and calcium release by subcellular fractions of smooth muscle. II. Kinetics of calcium uptake by microsomes and mitochondria from pig coronary artery and guinea pig ileum.

Calcium uptake by the microsomal and mitochondrial fractions of pig coronary artery and guinea pig ileum was studied in the presence of ATP, ATP plus oxalate and without ATP and oxalate. Microsomes and mitochondria of both smooth muscles were found to be unable to accumulate appreciable amounts of calcium in the absence of ATP. Oxalate noticeably stimulated the calcium uptake of the mitochondrial fraction from pig coronary artery but had little effect on calcium uptake by the microsomal fraction of this smooth muscle. The calcium uptake of microsomes and mitochondria from guinea pig ileum was not or only slightly enhanced by oxalate. There are typical kinetics regarding the time course and the extent of calcium uptake by microsomes and mitochondria from pig coronary artery and guinea pig ileum. In comparison, considerable qualitative and quantitative differences between both smooth muscles are observed. The high ATP-dependent calcium uptake capacity of the mitochondria from pig coronary artery and guinea pig ileum are a further argument for the hypothesis that these organelles may play an important role in the contraction-relaxation mechanism of smooth muscle.

Adenosine Triphosphate↗