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Biomedical subjects

C B Nielsen

Publications and source records attributed to C B Nielsen.

54 records · Page 3Linked to original sources
PubMed1989

A comparison of the relaxant effects of pinacidil in guinea-pig trachea, aorta and pulmonary artery.

The relaxant activity of pinacidil, a proposed K+ channel opener, was compared in isolated guinea-pig trachea, aorta and pulmonary artery. In preparations precontracted by histamine or PGF2 alpha, pinacidil produced complete tracheal relaxation but only partial relaxation of vascular tissues. The order of responsiveness was: pulmonary artery greater than trachea greater than aorta. The slope of the pinacidil concentration-effect (C/E) curve was much steeper in the tracheal than in the vascular preparations. The pinacidil C/E curves for relaxation were similar when the three types of preparations were precontracted by 124 mM K+. Pretreatment with pinacidil caused a parallel shift of the tracheal histamine C/E curve to the right, whereas the maximal response to histamine was markedly depressed in the pulmonary artery.

Animals↗
PubMed1989

Pinacidil uptake and effects in the isolated rabbit heart.

The myocardial accumulation of pinacidil showed one-compartment characteristics with a half-time of 1.11 min., whereas the disposition followed three-compartment kinetics with half-times for the relevant two redistributory and the terminal phases of 0.39, 1.51 and 5.44 min., respectively. At a steady-state drug concentration in the perfusate of 6.12 nmol ml-1, the average concentration of pinacidil in the myocardium was 20.6 nmol g-1. The accumulated amount could predictically be referred with 57% to a central and 31 and 12% to two peripheral (deeper) drug pools. The pharmacodynamic effects of pinacidil in the isolated perfused rabbit heart were studied at stepwise increasing concentrations from 0.15 to 100 microM. Coronary flowrate increased initially up to 24.5% at 1.5 microM pinacidil and then gradually decreased. Amplitude and velocity of contraction were both inhibited in a biphasic way up to 92.7 and 94.1%, respectively. Apparent dynamic steady states developed within 13-15 min. The computer-derived inhibitory Em-values related to the first phase were 49.2 and 52.4% and those related to the second phase were 111.7 and 108.3%, respectively. Heart frequency decreased monophasically and exhibited an inhibitory Em-value of 19.6%. Oxygen consumption decreased at pinacidil concentrations higher than 15 microM and the Em-value was 69.7%. The frequency-corrected QT-interval decreased biphasically and the related inhibitory Em-values were 8.6 and 58.7%. The QRS-interval did not change and the PQ-interval only showed a minor increase at the highest pinacidil concentration. Our findings are compatible with the concept of pinacidil being a potassium channel opener.

Animals↗
PubMed1988

Effects of pinacidil on guinea-pig airway smooth muscle contracted by asthma mediators.

Pinacidil is a new antihypertensive, direct vasodilator drug which has been classified as a K+ channel opener. The present study demonstrated a concentration-dependent relaxant activity of pinacidil in guinea-pig tracheal preparations. The potency and efficacy of pinacidil depended on the agent used to induce tracheal tone. Tracheal preparations with spontaneous tone or precontracted by different asthma mediators were completely relaxed by pinacidil. A high potency was found in spontaneously contracted preparations (EC50 = 7.8 x 10(-7) M). The EC50 values ranged from 2.3 to 5.4 x 10(-6) M in histamine-, PGF2 alpha- or LTC4-contracted preparations. When tone was induced by carbachol, the EC50 was 2.1 x 10(-5) M. In contrast, pinacidil produced incomplete relaxation and had a low potency in preparations contracted by 30 or 124 mM K+ Krebs solutions. This effect profile differed from that seen with beta 2-receptor agonists, xanthines and Ca2+ antagonists in guinea-pig trachealis and seems compatible with K+ channel opening as a primary mode of relaxation for pinacidil in airway smooth muscle.

Animals↗
PubMed1985

Diabetic retinopathy after one year of improved metabolic control obtained by continuous subcutaneous insulin infusion (CSII).

Twenty-four insulin dependent juvenile diabetics, with no or minimal background retinopathy, were randomly allocated to conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion (CSII) administrated by means of a portable pump. The metabolic control was significantly improved in the CSII group as compared to the CIT group. After one year, a progression of diabetic retinopathy (criterion: development of more than 2 microaneurysms) was observed in 3 of 12 patients in the CSII group and in 4 of 12 patients in the CIT group (P greater than 0.05). A tendency to more severe progression was observed in the CIT group. None developed soft exudates or retinal proliferations. Although no significant beneficial effect of pump treatment could be demonstrated, it seems safe to conclude that pump treatment does not accelerate progression of diabetic retinopathy in patients with no or minimal background retinopathy.

Adolescent↗
PubMed1985

Effect of alpha- and beta-receptor active drugs on corneal thickness.

Phenylephrine (10 mg/ml), phentolamine (10 mg/ml), isoprenaline (0.5 mg/ml) and timolol (5 mg/ml) were applied topically to one eye of volunteers with normal corneas, the other eye serving as a control. One drop of each drug was given twice a day for 3 or 4 days. Timolol was found to increase corneal thickness in both the medicated and the control eye. A significantly greater effect was noted on the eye receiving the drug directly. When isoprenaline was given for 3 days, a slight significant decrease in corneal thickness was found in both the medicated and the control eye, with the two eyes exhibiting a similar CCT change. The present results are suggestive of endothelial beta-receptor importance in the regulation of corneal thickness.

Adult↗
PubMed1982

Prostaglandin inhibition and central corneal thickness after cataract extraction.

The effect of systemically given naproxen (a qprostaglandin inhibitor) on central corneal thickness was studied in vivo, in the normal cornea, and in the cornea made artificially oedematous by cataract surgery. Only after cataract extraction could an effect be demonstrated. The post-surgical oedema was in this case reduced statistically significant corresponding to approximately 50% of control. Further the secondary rise in CCT on the third post-operative day as seen with non-medicated guttata corneas was absent after naproxen.

Adult↗
PubMed1980

On the optical measurement of a corneal thickness. I. Optical principle and sources of error.

The optical principle for the estimation of corneal thickness with a commonly employed method is considered. The theoretical relationship between the apparent and true corneal thickness is described in a simple manner. Based on the theoretical results it could be confirmed that physiological variations in refractive index and radius of the cornea induce an insignificant error in the corneal thickness estimate. The theoretical relationship between apparent and true corneal thickness was compared to the performance of two commercially available pachometers (Haag-Streit and Zeiss). The actual reading of the pachometers was found to be lower than the theoretical reading by a non-linear error amounting to about 0.010 and 0.100 mm at a true corneal thickness of 0.50 and 1.00 mm, respectively.

Anthropometry↗
PubMed1980

On the optical measurement of corneal thickness. II. The measuring conditions and sources of error.

The optical measurement of corneal thickness based on oblique viewing of the optical section of the cornea is complicated by the finite width of the incident slit beam. In this report the theoretical and practical aspects of the effect of the slit width on the thickness reading are analysed. In practice, it was not possible to make slit-width independent thickness readings which were reproducible from one observer to another. In addition, the observed slit-width error was found to vary from one patient to another. The lack of reproducible estimate of the corneal thickness is attributed to difficulties associated with an exact definition of the edges of the visible bands of the optical section, which are determined by biological properties of the cornea as well as perceptive properties of the observer. Although inter-observer errors up to 0.02 mm were found, the intra-observer error amounted to only 0.005-0.006 mm (SD) between consecutive readings. Presumably this high intra-observer reproducibility is the result of the auxiliary pin-lights used. Changes in corneal thickness, measured by the same observer, can therefore be determined with great accuracy.

Adult↗
PubMed1980

The effect of carbonic anhydrase inhibition on central corneal thickness after cataract extraction.

The influence of acetazolamide (a carbonic anhydrase inhibitor) on central thickness of the human cornea in vivo was studied. Corneal thickness as measured after cataract surgery was significantly increased by acetazolamide, if the specular microscopy revealed central corneal guttae, pre-operatively. When no guttae were seen by specular microscopy, no effect could be demonstrated.

Acetazolamide↗
PubMed1979

The influence of ionic strength, albumin and incubation time on the sensitivity of the indirect Coombs' test.

The sensitivity of the indirect Coombs' test was investigated using saline, albumin, or low ionic strength (LIS) in the incubation phase and an incubation time varying from 5 to 120 min. Titration of 41 antibodies showed that LIS always resulted in a higher or almost the same mean scores as the other solutions after the same incubation time. The maximum mean score was always higher with LIS than with saline and was reached after a shorter period of incubation, only 20--40 min even with the weakest antibodies. With LIS, a longer incubation time than 40 min resulted in a sudden decrease in mean score. The maximum mean score using saline or albumin was reached after 40--60 min incubation. The same mean score was obtained after only 15--20 min, when LIS was used. Albumin gave only slightly higher mean scores than saline.

Antibodies↗
PubMedDate not supplied

The conformations of locked nucleic acids (LNA).

We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases.

Carbohydrates↗
PubMedDate not supplied

Effect of insulin pump treatment for one year on renal function and retinal morphology in patients with IDDM.

The effect of strict metabolic control for 1 yr on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 yr, diabetes duration 10 +/- 6 yr) with Albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved and glomerular filtration rates (GFR) were found to decline (from 130 +/- 18 to 116 +/- 15 ml/min/1.73 m2, P less than 0.01). The mean value of urinary albumin excretion (UAE) was not statistically significantly reduced (from 15.3 +/- 24.1 to 6.8 +/- 1.5 mg/24 h, P greater than 0.1). In the CIT group both GFR and UAE values were unchanged. In all subjects before treatment we found a positive correlation between the metabolic status, estimated by the HbA1c values, and GFR as well as UAE values, respectively (r = 0.64, P less than 0.01 and r = 0.42, P less than 0.05). We conclude that elevated GFR values can be reduced toward normal level by insulin pump treatment for 1 yr. Retinal morphology was found to deteriorate in four of 12 CIT subjects and in three of 12 CSII subjects. However, the progression was mild and in most individuals only due to a slight increase in the number of microaneurysms. Pump treatment did not induce proliferation and "cotton-wool" exudates were not detectable in any pump subject after 1 yr of treatment. We conclude that CSII treatment for 1 yr was unable to stop the progression of retinopathy in individuals with minimal or no retinopathy on entering the study. On the other hand, pump treatment did not induce cotton-wool exudates or proliferation in these subjects as previously reported in subjects with more severe retinopathy before CSII treatment.

Adult↗