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Biomedical subjects

M K Hansen

Publications and source records attributed to M K Hansen.

At least 37 records · Page 2Linked to original sources

Single-dose pharmacokinetics of flumequine in halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus).

Flumequine was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously (i.v.) and orally (p.o.) at a dose of 10 mg/ kg bodyweight, and as a bath-treatment at a dose of 10 mg/L water for 2 h, using identical experimental designs. The study was performed in seawater with a salinity of 3% and a temperature of 10.3+/-0.4 degrees C (halibut) and 18.0+/-0.3 degrees C (turbot). Pharmacokinetic modelling of the data showed that flumequine had quite similar pharmacokinetic properties in halibut and turbot. Following intravenous administration, the volumes of distribution at steady state (Vss) were 2.99 L/kg (halibut) and 3.75 L/kg (turbot). Plasma clearances (Cl) were 0.12 L/kg (halibut) and 0.17 L/h x kg (turbot) and the elimination half-lives (t(1/2lambdaz)) were calculated to be 32 h (halibut) and 34 h (turbot). Mean residence times (MRT) were 25.1 h (halibut) and 22.2 h (turbot). Following oral administration, the t(1/2lambdaz) were 43 h (halibut) and 42 h (turbot). Maximal plasma concentrations (tmax) were 1.4 mg/L (halibut) and 1.9 mg/L (turbot), and were observed 7 h post administration in both species. The oral bioavailabilities (F) were calculated to 56% (halibut) and 59% (turbot). Following bath administration maximal plasma concentrations were 0.08 mg/L (halibut) and 0.14 mg/ L (turbot), and were observed 0 h (halibut) and 3 h (turbot) after the end of the bath. The bioavailability in halibut following a 2-h bath treatment was 5%.

Administration, Oral↗

Functional expression of rat VPAC1 receptor in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae was examined as host for heterologous expression of the G protein-coupled VPAC1 receptor. Rat VPAC1 receptor cDNA and two chimeric constructs encoding the yeast mating factor pre-pro alpha-leader peptide fused in-frame to rat VPAC1 receptor were expressed in yeast cells under control of a galactose inducible promoter. The rat VPAC1 receptor was fused to the HSV tag epitope to ensure proper immunological detection of the receptor. Crucial conditions for high-level expression of active rat VPAC1 receptor included growth in amino acid supplemented minimal medium, fusion to the yeast alpha-leader peptide and a temperature shift from 30 degrees C to 15 degrees C before promoter induction. Western blotting showed that the expressed receptor was highly glycosylated and a band of 47 kDa was obtained upon endoglycosidase H treatment. Binding with radioiodinated vasoactive intestinal polypeptide revealed a KD of 2.5 nM and an IC50 of 15 nM when displacing with unlabeled vasoactive intestinal polypeptide. VPAC1 receptor density quantified by Western blotting was 510 pmol/mg membrane protein of which only 66 pmol/mg were able to bind vasoactive intestinal polypeptide.

Animals↗

Subdiaphragmatic vagotomy does not block sleep deprivation-induced sleep in rats.

Cytokines, such as interleukin-1beta (IL-1beta), are involved in physiological sleep regulation and in the sleep responses to sleep deprivation. Sleep deprivation increases systemic cytokine levels and recent evidence suggests that cytokine-to-brain communication occurs via the vagus nerve. Furthermore, the vagus nerve plays a role in sleep responses elicited by feeding and vagal activity affects electroencephalographic (EEG) activity. Thus, this study examined sleep-wake activity and brain temperature (Tbr) responses to sleep deprivation in subdiaphragmatically vagotomized and sham-operated rats. In control rats, 6 h of total sleep deprivation significantly increased nonrapid eye movement sleep (NREMS), rapid eye movement sleep (REMS), and electroencephalographic slow-wave activity during nonrapid eye movement sleep. Brain temperature was significantly increased during the 6 h of sleep deprivation and decreased following sleep deprivation. Vagotomy had no significant effects on any of these variables. These results indicate that the subdiaphragmatic vagus nerve is not critical in the sleep and thermoregulatory responses after 6 h of sleep deprivation. Together with other data, the current results suggest that central pools of interleukin-1 are important in moderate sleep deprivation-induced sleep responses and that vagotomy does not disrupt the ability to increase sleep using a well-known sleep-inducing stimulus likely mediated by brain cytokines.

Animals↗

Vagotomy blocks the induction of interleukin-1beta (IL-1beta) mRNA in the brain of rats in response to systemic IL-1beta.

There is considerable interest in the mechanisms by which systemic cytokines signal the CNS to elicit centrally controlled biological actions. This study determined the effects of intraperitoneal injections of interleukin-1beta (IL-1beta) on IL-1beta mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA production in rat liver and brain using the reverse transcription-PCR. Saline or IL-1beta (0.5 microg/kg) was injected intraperitoneally in subdiaphragmatically vagotomized and sham-operated (SHAM) rats. All injections were performed at dark onset, and rats were killed 2 hr after the injection. In SHAM rats, IL-1beta increased IL-1beta mRNA levels in the liver, hypothalamus, hippocampus, and brainstem. Subdiaphragmatic vagotomy blocked the IL-1beta-induced increase in IL-1beta mRNA in the brainstem and hippocampus and significantly attenuated the increase in the hypothalamus. Vagotomy did not affect IL-1beta-induced IL-1beta mRNA production in the liver. IL-1RAP mRNA was highly expressed in each region examined; however, no significant differences in IL-1RAP mRNA production were found in any region after IL-1beta injection. The current results indicate that the vagus nerve is involved in transmitting cytokine signals to the brain and suggest that the induction of brain cytokines is a critical step in the pathway by which vagal-mediated signals result in centrally controlled symptoms of the acute phase response.

Animals↗

Sleep-associated changes in interleukin-1beta mRNA in the brain.

Much evidence implicates interleukin-1beta (IL-1beta) in sleep regulation. Two previous studies indicated that levels of IL-1beta in mRNA were affected by sleep. In the current study, levels of IL-1beta mRNA and IL-1 receptor assessory protein (IL-1RAP) mRNA were determined 1 h after the beginning of light and dark periods and after sleep deprivation, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and mutated internal standards. Daytime samples contained relatively more IL-1beta mRNA than nighttime samples, and levels of IL-1beta mRNA were higher after sleep deprivation. These changes occurred in the hypothalamus, hippocampus, cerebral cortex, and mesencephalon/pons. In contrast, the IL-1 RAP mRNA level did not seem to be affected by sleep.

Animals↗

Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats.

Feeding rats a cafeteria diet results in increased food intake and excess sleep. Furthermore, vagal afferent activity is altered by a variety of gastrointestinal factors, and vagal stimulation can induce sleep. We investigated, therefore, the hypothesis that the vagal nerve plays a critical role in mediating the sleep-inducing effects of cafeteria feeding. We examined the effects of a cafeteria diet on sleep, electroencephalographic (EEG) slow-wave activity (SWA), and brain temperature (Tbr) in control and vagotomized rats. EEG, electromyogram, and Tbr were recorded for 7 consecutive days. Day 1 was considered a baseline day; normal rat chow was available ad libitum. On days 2-4, the animals were fed, in addition to normal chow, a mixed, energy-rich diet (cafeteria diet). On days 5-7, the rats were again fed only normal rat chow. In control rats, the cafeteria diet resulted in an increase in non-rapid eye movement sleep (NREMS), which was the result of a significant lengthening of the NREMS episodes. In contrast, feeding vagotomized rats the cafeteria diet resulted in a decrease in NREMS. Cafeteria feeding decreased REMS and EEG SWA and increased Tbr in both control and vagotomized rats. These results suggest that an intact vagus plays a key role in the NREMS-inducing effects of the cafeteria diet.

Afferent Pathways↗

Vagotomy attenuates but does not prevent the somnogenic and febrile effects of lipopolysaccharide in rats.

The role of the vagus nerve in the somnogenic and pyrogenic effects of lipopolysaccharide (LPS) was studied in rats. Control rats (n = 8) and rats subjected to bilateral subdiaphragmal vagotomy (VX; n = 9) were injected with 100 micrograms/kg i.p. LPS at the beginning of the dark period. Sleep and brain temperature (Tbr) were recorded for 23 h after the injections. LPS caused increases in non-rapid eye movement sleep (NREMS) for 12 h after the injection in control rats. Sleep intensity, as indicated by the slow-wave activity (SWA) of the electroencephalogram during NREMS, was suppressed. LPS elicited biphasic Tbr responses: an initial hypothermia was followed by increases in Tbr that lasted for approximately 20 h. In vagotomized rats, the NREMS responses to LPS were blunted. The magnitude of the LPS-induced NREMS increases was about one-half of that seen in control rats, and these sleep responses lasted only for 6 h. LPS did not affect SWA in VX animals. VX completely abolished the hypothermic responses to LPS and shortened the duration of the hyperthermia. The results suggest that the subdiaphragmal vagi play an important, but not exclusive, role in the somnogenic and pyrogenic actions of intraperitoneally injected LPS.

Animals↗

Cafeteria feeding induces interleukin-1beta mRNA expression in rat liver and brain.

intake affects gut-immune function and can provide a strong intestinal antigen challenge resulting in activation of host defense mechanisms in the digestive system. Previously, we showed that feeding rats a cafeteria diet increases non-rapid eye movement sleep by a subdiaphragmatic mechanism. Food intake and sleep regulation and the immune system share the regulatory molecule interleukin-1beta (IL-1beta). Thus this study examined the effects of a cafeteria diet on IL-1beta mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA expression in rat liver and brain. Rats were fed normal rat chow or a palatable diet consisting of bread, chocolate, and shortbread cookies (cafeteria diet). After 3 days, midway between the light period of the light-dark cycle, rats were killed by decapitation. Feeding rats a cafeteria diet resulted in increased IL-1beta mRNA expression in the liver and hypothalamus compared with rats fed only the normal rat chow. In addition, cafeteria feeding decreased IL-1RAP mRNA levels in the liver and brain stem. These results indicate that feeding has direct effects on cytokine production and together with other data suggest that the increased sleep that accompanies increased feeding may be the result of increased brain IL-1beta. These results further suggest that cytokine-to-brain communication may be important in normal physiological conditions, such as feeding, as well as being important during inflammatory responses.

Animals↗

Three-dimensional reconstruction of port wine stain vascular anatomy from serial histological sections.

Port wine stains (PWSs) treated with a flashlamp-pumped pulsed dye laser show a variability in clinical response that is incompletely understood. To identify any vascular structure that might adversely affect treatment response, we obtained a three-dimensional reconstruction of the vascular anatomy of a non-responsive, light-purple superficial PWS on the forearm. The reconstructed PWS consisted of multiple clusters of small diameter (10-50 microns) blood vessels. We propose that this and similar structures, which have not been identified in the literature, have limited the efficacy of laser therapy. Further study is required to clarify the role of vessel clusters for laser treatment of PWSs, and the corresponding dosimetry necessary to clear non-responsive lesions. We expect that three-dimensional reconstruction of PWS vascular anatomy will provide the basis for (i) accurate PWS classification, (ii) guidance for selection of more effective laser dosimetry, and (iii) a standard against which to assess non-invasive diagnostic imaging techniques.

Adult↗

Subdiaphragmatic vagotomy blocks the sleep- and fever-promoting effects of interleukin-1beta.

The mechanism by which peripheral cytokines signal the central nervous system to elicit central manifestations of the acute phase response remains unknown. Recent evidence suggests that cytokines may signal the brain via the vagus nerve. To test this possibility, we examined sleep-wake activity and brain temperature (Tbr) after the intraperitoneal administration of saline or three doses (0.1, 0.5, and 2.5 microg/kg) of interleukin-1beta (IL-1beta) in subdiaphragmatically vagotomized (Vx) and sham-operated (Sham) rats. The lowest dose of IL-1beta (0.1 microg/kg) increased non-rapid eye movement sleep (NREMS) and slightly elevated Tbr in Sham rats; both responses were blocked in Vx animals. The middle dose tested (0.5 microg/kg) increased NREMS and Tbr in Sham animals; however, in Vx rats, the increase in NREMS was attenuated and the increase in Tbr was blocked. The highest dose of IL-1beta used (2.5 microg/kg) induced increases in NREMS, decreases in rapid eye movement sleep, and a hypothermic response followed by a biphasic fever; these responses were similar in both Sham and Vx rats. These data provide strong evidence that the subdiaphragmatic vagus plays an important role in communicating both sleep and fever signals to the brain. However, there is clearly an alternative pathway by which IL-1 can signal the brain; whether it occurs through activation of other vagal afferents or through direct or indirect actions on the brain remains unknown.

Animals↗

Acetylcholine activates a nicotinic receptor and an inward current in dorsal motor nucleus of the vagus neurons in vitro.

This study examines the effect of acetylcholine (Ach) on parasympathetic vagal neurons in the dorsal motor nucleus of the vagus (DMNX). Patch-clamp techniques were utilized to examine voltage and ligand-gated currents in visualized DMNX neurons in an in vitro slice. Ach (100 microM) activated an inward current, -196.4 +/- 56.9 pA at -80 mV (n = 15) that was accompanied by a decrease in membrane resistance of 48.6 +/- 9.2% in a population of DMNX neurons. The reversal potential for this ligand-gated current was -11.3 +/- 11.5 mV. The specific agonist nicotine (200 microM) elicited similar responses. Nicotine decreased membrane resistance by 60.9 +/- 4.3% and activated an inward current (-215.7 +/- 45.7 pA at -80 mV) that reversed at -12.7 +/- 20.4 mV (n = 16). Bethanecol (100 microM), a specific muscarinic agonist, had no effect. Neither Ach or nicotine had any effect on the voltage-gated sodium and outward potassium currents present in these neurons.

Acetylcholine↗

Clinical comparison of the XPERT non-contact tonometer and the conventional Goldmann applanation tonometer.

Intraocular pressure (IOP) in the right eye of 113 patients was measured with one XPERT NCT air-puff non-contact tonometer (XPERT) and compared with IOP measured with one Goldmann applanation tonometer (GAT). Precision of the methods was judged by variance analysis, indicating that GAT was slightly more precise than XPERT. The slope of the linear relationship between the methods did not differ significantly from 1.0. Mean difference between the methods was 0.92 mmHg, XPERT measuring lower than GAT, p = 0.00017. The intra-individual difference between methods ranged from -8.00 to 8.67 mmHg, and standard deviation (SD) of differences was 2.52 mmHg. The 95% limits of agreement between the two methods were -5.85 to 4.01 mmHg. The SD of differences is of approximately the same size as previous XPERT vs GAT as well as previous GAT vs GAT studies.

Adolescent↗

Ultrasonographic, three-dimensional scanning for determination of intraocular tumor volume.

Important prognostic information may be gained from knowing the volume of intraocular tumors, such as choroidal melanomas. To measure such volume, we developed an ultrasonographic 3-D scanning system, which operates by an axial, back and forth, half-turn rotation of a commercial sector scanning transducer, applied directly onto a closed eyelid. Control of movement, data acquisition, and image analysis are accomplished by means of a microcomputer and application-specific software. The elapsed time for scanning and digitizing 11 cross-sectional images across a human eyeball, is 4 sec. Outlines of specific structures are traced manually. The system was tested through repeated, in vitro measurements of known volumes of meat; the mean variation coefficient of these measurements was 2.8%. While accurate estimates were obtained on volumes between 0.01-0.25 ml, these are linearly dependent on gain setting. A patient with a choroidal melanoma was scanned repetitively. The procedures of scanning and tracing contributed about equally to the total variance. This method of scanning allows repeatable, reliable, and easily generated measurements of a tumor's volume and, thus, has great potential for use in the diagnosis and treatment of malignant, intraocular tumors.

Choroid Neoplasms↗

[Treatment of esophageal achalasia using Heller's method].

The long-term results after Heller's myotomy for oesophageal achalasia were illustrated by questionnaire sent to 38 out of the original 47 patients submitted to operation during the ten-year period 1.7.1973-30.6.1983. Nine patients had died from other causes during the follow-op period. The minimum period of observation for the remaining patients was five years and the mean period of observation was 10.3 years. Thirty-six questionnaires were returned (95%). 75% of the patients were satisfied with the results of operation but only 25% were symptom-free. The commonest symptom was dysphagia (56%) followed by reflux problems (50%). Every third patient had discomfort from the scar. All of the 25% of the patients who were not satisfied with the result of operation had dysphagia. On the basis of these observations, the authors consider that Heller's myotomy should be reserved for patients on whom dilatation treatment has proved unsatisfactory.

Adolescent↗

Spontaneous pneumothorax and fibrin glue sealant during thoracoscopy.

The prophylactic treatment of the application of fibrin glue to the pulmonary surface during thoracoscopy in idiopathic spontaneous pneumothorax resulted in rapid and total pulmonary expansion in 33 of 35 patients. The 2 failures were due to apical cysts larger than 2 cm. The successfully treated patients were hospitalized for a median of 4 days (range 2-12). No complications were observed. All regained full working capacity within 1 month of discharge. Post-treatment X-ray examination of the chest was uniformly normal. During an observation time ranging from 7-24 months (median 12 months), 3 recurrences (9%) were seen at 7, 12, and 16 months, respectively. The treatment seems (1) to reduce the need for thoracotomy (2) to be associated with a high success rate, short and long-term, (3) to minimize the duration of hospital stay and (4) not to disturb the normal pleuro-pulmonary anatomy.

Administration, Inhalation↗

Transvenous retrieval of intracardiac catheter fragments.

Six cases of catheter embolism are presented, and various techniques of retrieving these foreign bodies from the heart are described. The techniques may be carried out under local anaesthesia. They are rapid, safe and enable the patients to avoid thoracotomy.

Adolescent↗