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C Friis

Publications and source records attributed to C Friis.

49 records · Page 3Linked to original sources
PubMed1984

Pharmacokinetics and metabolism of trimethoprim in neonatal and young pigs.

The pharmacokinetics and metabolism of trimethoprim (TMP) was studied in newborn, 1 and 8-week-old piglets after intravenous administration of 5 mg/kg. Kinetic parameters were calculated using a two-compartment open model. Steady-state volume of distribution increased from 0.78 L/kg at birth to 1.32 L/kg at 1 week, and 1.83 L/kg at 8 weeks due to changes in plasma protein binding and tissue accumulation. Elimination half-life decreased from 485 minutes at birth to 224 minutes at 1 week, and 120 minutes at 8 weeks leading to a rise in body clearance from 1.18 to 11.8 ml/min/kg during the same period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both metabolic capacity and renal function. Metabolism was the main contributor to the elimination of TMP at all ages, although the major metabolic pathway, O-demethylation and subsequent conjugation, was only slightly developed at birth. The capacity to form conjugates with either glucuronic acid or sulphate appeared to be at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in all groups.

Aging↗
PubMed1981

Postnatal development of renal function in piglets: changes in excretory pattern of sulphachlorpyridazine.

The renal excretion of sulphachlorpyridazine (SCP) was measured in 34 unanaesthetized piglets 5-74 days of age. The renal handling of SCP was found to include: glomerular filtration, active tubular secretion and passive reabsorption. During the age period studied the clearance of ultrafiltrable SCP increased several times more than GFR (inulin clearance) indicating that the balance between filtration, secretion and reabsorption is changed during postnatal maturation. The age-related change in clearance ratio possibly reflects both a greater increase in tubular secretory capacity than in glomerular filtration and a relative decrease in the passive reabsorption.

Acetylation↗
PubMed1980

Postnatal development of the pig kidney: ultrastucure of the glomerulus and the proximal tubule.

The detailed anatomy of the structures forming the glomerular filtration barrier and the proximal tubule was studied during postnatal development of the pig kidney. Development of the glomerular filtration barrier included three processes: Formation of visceral epithelial foot processes, flattening and fenestration of the endothelium and formation of a common epithelial and endothelial basal lamina. During formation of foot processes the distribution pattern of aggregated filaments in the epithelial cells was changed, suggesting that the filaments participate in the elongation of the foot processes. In the immature glomerulus the endothelial fenestrae were closed by thin diaphragms which disappeared during differentiation of the endothelium. Microvilli were observed in the proximal tubule cells in an early developmental stage, presumably before onset of glomerular filtration. Few cellular organelles were seen in the tubule anlage but the number of mitochondria, apical vacuoles and lysosome-like bodies increased markedly during maturation. Dense bodies identified as peroxisomes first appeared in a late development stage. The formation of nephrons continued up to about 3 weeks of age; after this time the morphological development was a differentiation of nephrons already present. The present observations, together with results of an accompanying functional study, demonstrate that changes in functional parameters reflect the structural development.

Aging↗
PubMed1979

Postnatal development of renal function in piglets: glomerular filtration rate, clearance of PAH and PAH extraction.

Glomerular filtration rate (GFR), estimated as clearance of inulin, and clearance of p-aminohippuric acid (CPAH) were measured in 32 unanaesthetized piglets 1--62 days of age. During this period of time, GFR increased from 0.27 to 0.59 ml/min/g kidney and CPAH increased from 1.02 to 1.72 ml/min/g kidney. At 8 weeks of age, GFR and CPAH equaled adult values. In addition, renal PAH extraction (EPAH) was estimated in 12 anaesthetized piglets aged 1--79 days. EPAH increased from 0.75 at birth to 0.86 (adult value) at 3 weeks of age. The result shows a postnatal increase in renal functions in piglets, but the development from birth to adult level was less pronounced than seen in other animal species.

Animals↗
PubMed1979

Porcine nephropathy induced by long-term ingestion of ochratoxin A.

Nine pigs were fed crystalline ochratoxin A in their feed at a concentration of about 1 mg/kg. Three pigs and their controls were killed after 3 months and 6 pigs and controls were killed after 2 years. A decrease of the ratio TmPAH/CIn, increased urinary glucose excretion and decreased ability to concentrate urine, occurred within a few weeks and aggravated slightly during the 2-year period. Changes in renal structure, characterized by degeneration and atrophy of proximal tubules, interstitial fibrosis and hyalinization of glomeruli, were progressive during time of exposure, but terminal renal failure was not reached. The kidney, liver, muscular and adipose tissue contained 3 to 27 microgram ochratoxin A/kg after 3 months of exposure. No further accumulation of ochratoxin A residue was found after 2 years of exposure.

Animals↗
PubMed1977

Perfusion fixation of kidneys in adult pigs for electron microscopy.

In five female pigs, weighing approximately 100 kg, laparotomy was made under surgical anesthesia. One kidney was removed for immersion fixation and enzyme histochemistry, while the other kidney was fixed by vascular perfusion without prior interruption of the blood flow. A step-by-step description is given of the perfusion procedure, which requires three assistant. Prior to perfusion, heparin was given in order to prevent intravascular coagulation. 1% glutaraldehyde in Tyrode's solution was used as perfusion fluid. Polyvinylpyrrolidone 2.5% was added in order to adjust the colloid osmotic pressure of the perfusion fluid to that of the blood. Perfusion was maintained for 5 min. The tubules appeared with open lumina, and the proximal tubular cells had evenly arranged brush borders and both lateral and intercellular spaces were narrow and of constant width.

Animals↗
PubMedDate not supplied

Penetration of amoxycillin into the respiratory tract tissues and secretions in pigs.

The pharmacokinetic properties of amoxycillin, and its penetration into respiratory tract tissues (alveolar macrophages, bronchial secretions, bronchial mucosa, lung tissue and lymph nodes), were determined in 20 healthy female pigs weighing 29 to 55 kg, after a single intravenous dose of 8.6 mg kg(-1) bodyweight. Following intravenous administration the plasma concentration-time curves were best described by a three-compartment open model. The elimination half-life and the mean residence time were 2.5 and 1.4 hours, respectively. The volume of distribution at steady state was 0.52 litres kg(-1), and the body clearance was 0.40 litres hour(-1) kg(-1). In all structures (except alveolar macrophages) amoxycillin concentration peaked at the first sampling point, one hour after drug administration. The tissue to plasma ratio (based on AUC values) were 0.33 for bronchial secretions, 0.37 for bronchial mucosa, 0.39 for lung tissue and 0.68 for lymph nodes. Traces of amoxycillin were found in alveolar macrophages, but the concentrations were below the limit of quantification. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than the concentration in plasma, resulting in increasing secretion- and tissue-to-plasma concentration ratios.

Amoxicillin↗
PubMedDate not supplied

Penetration of amoxycillin to the respiratory tract tissues and secretions in Actinobacillus pleuropneumoniae infected pigs.

The pharmokinetic properties of amoxycillin, and its penetration into respiratory tract tissue, were determined in 18 Actinobacillus pleuropneumoniae infected pigs, after a single i.v. dose of 8.6 mg amoxycillin kg(-1) bodyweight. Pleuropneumoniae was produced experimentally in pigs by an aerosol infection model. The infection created a homogeneous response, characterised by depression of breathing and increased body temperature. The clinical symptoms were accompanied by increased haptoglobin levels and circulating white blood cell counts. At necropsy the findings were characterised by a bilateral fibrinous pleuropneumonia. Twenty hours after infection, the pigs were administered amoxycillin i.v. The plasma concentration-time curve was described by a three compartment open model. The mean residence time and the elimination half-life were 1.5 and 3.4 hours, respectively. The steady-state volume of distribution was 0.67 litres kg(-1), and the clearance was 0.46 litres kg(-1) hour(-1). There were no significant differences between these values and those reported previously for healthy pigs. The concentration of amoxycillin in bronchial secretions, lung tissue and diseased lung tissue peaked two hours after intravenous drug administration, while amoxycillin concentration in pleural fluid, lymph nodes and tonsil tissue peaked at the first sampling point one hour after drug administration. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than amoxycillin concentration in plasma, resulting in an increasing tissue-to-plasma concentration ratio. The distribution ratios (AUCtissue/AUCplasma) was 0.53 for bronchial secretions, 0.44 for pneumonic lung tissue, 0.42 for lung tissue, 1.04 for pleural fluid, 0.58 for lymph nodes and 0.37 for tonsil tissue. The distribution of amoxycillin to secretions was increased compared with that previously reported for healthy pigs, while only minor changes were observed in lung tissue.

Actinobacillus Infections↗
PubMedDate not supplied

Three views of microbial genomes.

We describe here GenomeAtlases as a method for visualising three different aspects of complete microbial chromosomes: repeats, DNA structural characteristics, and base composition. We have applied this method to all publicly available genomes, and find a general strand preference of global repeats. The atlas for the Mycoplasma genitalium genome is presented as an example, and results from all three views are consistent with known characteristics of the genome.

Base Composition↗
PubMedDate not supplied

Studies on the renal kinetics of growth hormone (GH) and on the GH receptor and related effects in animals.

Growth hormone (GH) is filtered through the kidney, and may exert effects on renal function when presented via the circulation. Investigations on kidney-related aspects of GH are increasing in number. Using in vitro and in vivo approaches, the present study attempted to provide answers to a number of unresolved or debated issues. In vitro, we detected both GH and type 1 IGF receptors (R) in a porcine renal epithelial cell line. The saturation and down regulation kinetics of the GH-R indicate that it has the properties of a classical GH-R. Furthermore, the simultaneous presence of GH-R and IGF-R on a phenotypically homogeneous cell line suggests the presence of GH-induced auto-/paracrine IGF-1 bioactivity in the kidney. Experiments with isolated proximal rabbit tubules incubated with physiological concentrations of 125I-GH demonstrated a time-and dose-dependent increase in unlabelled GH-displaceable cell-associated radioactivity, lending support to the concept of GH mediating its renal effects via proximal tubular GH-R. Short term administration of GH to rats and humans elicited electrolyte and water retention that may cause edema in adults. In the present study, long term administration of GH to rats caused only a minor increase in serum phosphate levels, with no changes observed in the renal electrolyte clearance. During the first 4 days of GH treatment in rats, no change in plasma renin activity was detected and we were thus unable to confirm the hypothesis that the renin-angiotensin system is responsible for the early phase of GH-associated fluid retention. Pharmacokinetically, when GH was administered to rats with functional disconnection of the kidneys as a model of renal insufficiency, the whole body clearance of GH decreased by ca. two thirds, and was reflected by an increase in the mean residence time and AUCplasma for GH. The plasma half-life, however, was not significantly affected, suggesting that the volume of distribution (Vd) had decreased for the GH administered to the renally compromised animals. A renal contribution to the Vd was visualized as intense radioactive staining in the kidney region on whole body autoradiographs (WBA) of rats dosed with 125I-labelled hGH. The liver region was also intensely stained. Kidney-associated radioactivity was found to be related not only to glomerular filtration, but also to peritubular uptake, since the renal clearance of free GH was found to exceed the GFR.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗