Poul Nielsen

LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition

A novel class of nucleic acid analogues, termed LNA (locked nucleic acids), is introduced. Following the Watson–Crick base pairing rules, LNA forms duplexes with complementary DNA and RNA with remarkably increased thermal stabilities and generally improved selectivities.

Lna (Locked Nucleic Acid)

Abstract LNA (Locked Nucleic Acid) forms duplexes with complementary DNA, RNA or LNA with unprecedented thermal affinities. CD spectra show that duplexes involving fully modified LNA (especially LNA:RNA) structurally resemble an A-form RNA:RNA duplex. NMR examination of an LNA:DNA duplex confirm the 3′-endo conformation of an LNA monomer. Recognition of double-stranded DNA is demonstrated suggesting strand invasion by LNA. Lipofectin-mediated efficient delivery of LNA into living human breast cancer cells has been accomplished.

Relationships between molecular structure and excretion of drugs

Abstract Drugs and their metabolites are usually eliminated from the body by excretion in the urine or bile or sometimes both, but other pathways may be used, such as milk, saliva, sweat or the expired air. The excretion can take place by passive or by active processes, and is influenced by the physico-chemical properties of the drug.

Metabolism of Sulphadiazine in Goats

1. Following intravenous administration of sulphadiazine (2-sulphailamido-pyrimidine) to goats, unchanged sulphadiazine comprised the major part of the total sulphonamide in blood plasma, milk and urine samples. 2. Relatively small amounts of N4-acetysulphadiazine were excreted in milk and urine. The amount of conjugated metabolites in urine was small, but was comparatively large in the milk samples. 3. A new metabolite, 2-sulphanilamido-4-hydroxyprimidine, which comprised about 15% of the total sulphonamide in urine was isolated.

Metabolism of sulfadiazine in neonatal and young pigs: Comparative in vivo and in vitro studies

Metabolism of sulfadiazine (SDZ) was studied in vivo and in vitro during postnatal development of piglets in order to examine whether in vitro metabolism approaches the in vivo situation. Experiments were performed in 1-day-, 8-day- and 60-day-old piglets. In vivo: 14C-SDZ was injected intravenously and urine and tissue samples collected after 3 hr. Urinary excretion data as well as data from liver and kidney tissue indicated a relatively high capacity for acetylation at birth, while the capacity for oxidation is low during the first week of life. At 60 days of age the acetylation and oxidation of SDZ is equal each accounting for about 20% of the amount excreted in urine. In vitro: Incubation of subcellular fractions of liver and kidney showed that acetylation of SDZ in liver reached maximum within 1 week. Oxidative activity was absent at 1 day, present at a low level at day 8, and at a high level at day 60. Neither acetylation nor oxidation of SDZ took place in kidney. The results show a close correlation between in vivo and in vitro results with respect to the developmental pattern seen in piglets during the postnatal period of life.

Severe paroxysmal hypertension induced by a subconscious Valsalva-like manoeuvres

We describe the case history of a 32 year old male with severe paroxysmal hypertensive spikes when there was an increase in diastolic blood pressure to 150–200 mmHg. These spikes occurred during rest and especially during modest exercise. They were associated with headache and dyspnoea and were resistant to antihypertensive medication. After 5 years of observations and investigations he underwent further 24-h intra-arterial blood pressure monitoring and physiological testing. The 24-h blood pressure profile was near normal at rest. The observed hypertensive spikes seemed to be induced by involuntary Valsalva-like manoeuvres. This had not been detected previously by the investigators and the patient was unaware of inducing these manoeuvres.

Removing Formaldehyde from Embalmed Cadavers by Percolating the Body Cavities with Dilute Ethanol

Formaldehyde was removed from embalmed animal cadavers by pumping ethanol (20%) through the pleural and peritoneal cavities of 4 goats, 4 cows and 4 horses. The goats were percolated intermittently for 7 days and the large animals continuously for 72 h. Just after opening the body cavities, samples of air close to the organs were collected and analyzed for formaldehyde using a spectrofluorimetric method. The concentration of formaldehyde in the air samples was in goats 0.45 +/- 0.44 microgram/l (mean +/- SD), cows 0.42 +/- 0.29 microgram/l and horses 0.43 +/- 0.25 microgram/l.

A New Synthetic Approach Towards α- and β-LNA (Locked Nucleic Acids)

Abstract A bicyclo[2.2.1] phenyl thioglycoside was efficiently synthesised and introduced as the key synthon in a novel method for convergent synthesis of β-LNA-nucleosides as well as their α-configurated isomers. An acid-induced ring-opening reaction on the corresponding bicyclo[2.2.1] methyl furanoside is also described.

Synthesis of novel 3'-C-branched 2'-deoxynucleosides. Incorporation of 3'-C-(3-hydroxypropyl)thymidine into oligodeoxynucleotides

The methyl glycoside derivatives 4, 6, 10 and 32 have been used as precursors for the synthesis of novel 3′-C-alkyl-modified α- and β-2′-deoxynucleosides. Using an alternative linear strategy, 3′-C-methyl- and 3′-C-azidomethyl-modified thymidines 16 and 17 have been synthesized. Hybridization experiments with oligodeoxynucleotides containing 3′-C-(3-hydroxypropyl)thymidine monomers are reported.

Home readings of blood pressure in hypertension.

Out-patient-clinic blood pressure (OPC-BP) was compared to blood pressure taken at home (Home-BP) measured three times daily during a two week period in 66 consecutively referred hypertensive subjects. A semi-automatic manometer was used (TM-101) which included a microphone for detection of Korotkoff sounds, self-deflation of cuff pressure and digital display of blood pressure. Mean difference between OPC-BP and Home-BP was systolic +14 mmHg (range -20/+100 mmHg) and diastolic +5 mmHg (range -27/+28 mmHg). Although a significant correlation could be demonstrated between Home-BP and OPC-BP, the inter-individual scatter was pronounced. There was no preponderance of patients with hypertensive organ damage among those with high OPC-BP or Home-BP. It is proposed that home readings should be included in the assessment and control of patients with hypertension, especially among badly controlled subjects and those with borderline hypertension.