Biomedical subjects

J Dinesen

Publications and source records attributed to J Dinesen.

14 recordsLinked to original sources

PubMed1990

DNA intercalating properties of tetrahydro-9-aminoacridines. Synthesis and 23Na NMR spin-lattice relaxation time measurements.

A series of 9-(arylamino)-1,2,3,4-tetrahydroacridines, including the tetrahydro m-AMSA [N-[4-(acridin-9-yl-amino)-3- methoxyphenyl]methanesulfonamide] derivative, has been synthesized. 23Na NMR spin-lattice relaxation rate (1/T1) measurements have been used to study whether these hydrogenated acridines were capable of intercalative binding to calf thymus DNA. The results have been compared to corresponding measurements for 9-aminoacridine, m-AMSA, and MgCl2. All compounds studied were capable of intercalative binding to DNA. However, it was found that the interaction was strongly influenced by substituents on the 9-arylamino group. Thus, tetrahydro m-AMSA was found to intercalate much more weakly with DNA than m-AMSA. Removal of the 3'-methoxy substituent of the 9-arylamino group resulted in intercalation in DNA that was almost as strong as that for m-AMSA.

Aminacrine↗

PubMed1989

[Isovaleric acidemia].

The three first cases of isovaleric acidemia diagnosed in Scandinavia are described. The disorder is characterized by periodic vomiting, lethargy and coma accompanied by ketoacidosis and a "sweaty feet" odour. These attacks are often triggered of by upper respiratory tract infections or by ingestion of large amounts of protein. Often there are feeding difficulties because these children have aversion to protein-containing foods. Isovaleric acidemia can be subdivided into two types: an acute neonatal form and a chronic intermittent form. The basic defect is deficient activity of isovaleryl-CoA dehydrogenase, resulting in increased urinary excretion of mainly isovaleryl-glycine and 3-hydroxy-isovaleric acid. The defective gene is assigned to the long arm of chromosome 15, and at least five different mutations among 15 patients have been demonstrated. Therapy is symptomatic with correction of the metabolic acidosis and protein restriction and long term treatment with oral glycine and possibly carnitine.

Acidosis↗

PubMed1989

Sodium-23 NMR spin-lattice relaxation rate studies of mono- and bis-intercalation in DNA.

23Na spin-lattice relaxation rate (1/T1 = R1) measurements have been used to study the intercalation of a series of 9-aminoacridine derivatives in DNA. The 23Na relaxation rate is strongly dependent upon the amount of intercalator added to a sodium DNA solution. The results are analyzed by a combined use of the ion condensation theory and the quadrupolar relaxation theory of polyelectrolyte solutions. This interpretation shows that the major effect in lowering the relaxation rate by intercalation is not due to the release of sodium ions but is caused by a substantial decrease in the relaxation rate Rb for the remaining bound sodium ions. Likewise, titration of NaDNA solutions with MgCl2 shows that condensation of Mg2+ on the DNA double helix reduces Rb. A good agreement between experiment and theory is found if the average lengthening following intercalation of a 9-aminoacridine moiety is assumed to be approximately 2.7 A. The distinction between mono- and bis-intercalation is clearly indicated by the results. The two bis-intercalating drugs examined are found to bis-intercalate only up to r less than or equal to 0.02. For r greater than 0.02 the drugs apparently mono-intercalate.

Aminoacridines↗

PubMed1987

Serum profiles and short-term metabolic effect of pituitary and authentic biosynthetic human growth hormone in man. A double-blind cross-over study.

In a double-blind cross-over study we compared pituitary and methionine-free biosynthetic human growth hormone (P-hGH and B-hGH) with respect to pharmacokinetics and short-term metabolic effects in 9 hypopituitary children. They treated themselves for 4 weeks with 2 IU sc daily at 20.00 h. After admittance to hospital 2 IU was given: im the first day, and sc the second. They then switched over to the alternative preparation. The serum profiles of B- and P-hGH were identical. Comparing im and sc absorption, the latter was slower and resulted in smaller areas under the curves, indicating greater local degradation. Both preparations caused identical increases in somatomedin-C, but slightly more sustained after sc injection. Plasma glucose, plasma glucagon, and serum insulin fluctuated within normal ranges. The glucose profile pointed at a modest anti-insulin effect of hGH when given in the morning. The concentration in the blood of lactate, alanine, glycerol and B-OH-butyrate, and in serum of triglyceride, cholesterol and carbamide revealed no abnormalities with either hGH preparation. Finally, no development of anti-GH or E. coli polypeptide antibodies was seen. In conclusion, the pharmacokinetics and short-term metabolic effects of B-hGH and P-hGH were identical.

Adolescent↗

PubMed1986