Biomedical subjects

Anders Thörne

Publications and source records attributed to Anders Thörne.

12 recordsLinked to original sources

PubMed2006

The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects.

In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period (r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.

Adult↗

PubMed2005

Effectiveness of a new carrier-bound fibrin sealant versus argon beamer as haemostatic agent during liver resection: a randomised prospective trial.

BACKGROUND AND AIMS: A new carrier-bound fibrin sealant, TachoSil, is expected to be efficacious and safe as a haemostatic treatment in hepatic resection. DESIGN: A prospective, randomised, open and controlled multicentre trial with intraoperative as well as postoperative assessment of efficacy and a 1 month follow-up period. SETTING: Tertiary care centres. PATIENTS/METHODS: One hundred and twenty-one patients requiring secondary haemostasis during planned liver resection. Patients with coagulation disorders and patients with persistent major bleeding after primary haemostatic measures were excluded. INTERVENTION: Application of either carrier-bound fibrin sealant (n=59) or argon beamer (argon beam coagulator) (n=62) as secondary haemostatic treatment. MAIN OUTCOME MEASURE: Time to intraoperative haemostasis. RESULTS: There was a significant superiority of TachoSil over argon beamer with regard to time to haemostasis (3.9 min, median 3.0, range 3-20 min vs 6.3 min, median 4.0, range 3-39 min) (P=0.0007). Haemoglobin concentration of drainage fluid was significantly lower on day 2 after surgery in TachoSil patients (1.1 mmol/l) than in argon beamer patients (2.3 mmol/l) (P=0.012). Overall, the frequency and causality of adverse events did not differ between the two treatment groups. CONCLUSION: TachoSil is superior to argon beamer in obtaining effective and fast intraoperative haemostasis. The safety data show TachoSil to be tolerable and safe for haemostatic treatment in liver resection.

Drug Carriers↗

PubMed2005

Effect of carbon dioxide pneumoperitoneum on development of atelectasis during anesthesia, examined by spiral computed tomography.

BACKGROUND: Anesthesia per se results in atelectasis development in the dependent regions of the lungs. The effect of pneumoperitoneum on atelectasis formation is not known. The aim of the current study was to measure by spiral computed tomography the effect of carbon dioxide pneumoperitoneum for laparoscopic surgery on the development of atelectasis, overall lung volume, and regional tissue volumes of gas and tissue. METHODS: Seven patients (American Society of Anesthesiologists physical status I), scheduled to undergo laparoscopic cholecystectomy, were observed. After induction of anesthesia, the patients were mechanically ventilated and positioned supine on the computed tomography table. Tomography of the lungs (10 mm spiral) was performed before and 10 min after induction of carbon dioxide pneumoperitoneum at an intraabdominal pressure of 11-13 mmHg. The Student t test was used for statistical analysis. A P value less than 0.05 was considered significant. RESULTS: Induction of pneumoperitoneum increased the mean atelectasis volume in the dependent lung regions by 66% (range, 11-170%). The overall lung volume and gas as well as tissue volume significantly decreased. Relative to the total lung volume, lung tissue volume increased, while gas volume decreased significantly. Both upper and lower lobes reacted the same way. A cranial displacement of the diaphragm between 1 and 3 cm (mean, 1.9 cm) was registered. CONCLUSION: Pneumoperitoneum at an intraabdominal pressure level of 11-13 mmHg increased the volume of atelectasis. Because lung tissue volume increased in the lung, there may have been an opening of previously closed vessels, which could explain previously seen increase in arterial oxygenation after induction of pneumoperitoneum.

Adult↗

PubMed2004

Indium-111-labelled donor-lymphocyte infusion by way of hepatic artery and radio-frequency ablation against liver metastases of renal and colon carcinoma after allogeneic hematopoietic stem-cell transplantation.

BACKGROUND: In patients with metastatic solid cancer, antitumor effects occur after allogeneic stem-cell transplantation (SCT). However, this treatment is not as effective in the liver as against pulmonary and lymph-node metastases. To intensify the effect of donor-lymphocyte infusions (DLI) against liver metastases, intra-arterial (IA) cell injection by way of the hepatic artery (HA) can be used. METHODS: To trace infused cells, three patients with colorectal, three with renal, and one with breast carcinoma were treated with Indium-111 (111-In)-oxinate-labeled lymphocytes. Four patients received the DLI IA, all after radio-frequency ablation (RFA) of liver metastases. Three patients with other metastases received 111-In DLI intravenously (IV). One of them had RFA before SCT. RESULTS: Localization of the IA 111-In DLI activity on scintigrams homed to the liver. After IA injection, the liver to sternum ratio of radioactivity was higher compared with IV injection. Cells (CD3+, 19+, and 56+) of donor origin in biopsies of liver metastasis in two patients treated with IA injection increased to 80% to 100%. Two of four patients treated using the IA DLI showed stable size and number of liver metastases for 5 and 21 months, respectively. Both are alive 18 and 34 months after SCT. Two of three patients receiving DLI IV are doing well, with a stable metastatic disease or still without metastases 21 and 20 months after cell infusions (26 and 34 months after SCT), respectively. Three patients died because of progressive disease. CONCLUSION: When infused by way of the HA, 111-In-labeled lymphocytes home to the liver and its metastases. The liver metastasis infiltrating cells of donor origin increased. DLI by way of the HA combined with RFA may be used to treat liver metastases after SCT.

Adult↗

PubMed2004

The synthesis rate of albumin decreases during laparoscopic surgery.

In previous studies, a decline in total liver protein synthesis during elective laparoscopic surgery has been observed. However, when albumin synthesis was measured in parallel no apparent influence of the procedure was detected. The aim of the present study was to specifically investigate the effect of a laparoscopic procedure on albumin synthesis. Female (n = 9) patients scheduled for elective laparoscopic cholecystectomy as a consequence of cholecystolithiasis were investigated. The fractional synthesis rate (FSR) of albumin was investigated twice in each patient, before and during surgery (2-3 h apart), employing L-[2H5]phenylalanine and gas chromatography mass spectrometry. The FSR of albumin decreased from 7.3 +/- 1.2% per day before surgery to 6.2 +/- 1.4% per day during the procedure (P<0.01), whereas the corresponding absolute synthesis rates of albumin decreased from 114 +/- 24 to 86 +/- 16 mg kg(-1) day(-1), respectively (P<0.001). In conclusion, the synthesis rate of albumin decreased during a laparoscopic surgery procedure. However, the characteristics for this decrease differ from those previously observed for total liver protein synthesis.

Adult↗

PubMed2004

Age-dependent regulation of lipogenesis in human and rat adipocytes.

The regulation of adipocyte metabolism is of importance for adipose tissue growth and therefore also for the development of obesity. This study was designed to investigate the regulation of basal and insulin-induced lipogenesis, glucose transport, and glucose transporter protein expression in human and rat adipocytes from different age groups. The study included 21 infants, 21 children, nine adults, and 80 male weaned and 20 male adult Fischer rats. The lipogenesis experiments were performed under conditions at which glucose transport is rate limiting. Basal lipogenesis was approximately three times higher in infants and children than in adults, whereas insulin-induced lipogenesis was two times higher in infants than in children and adults. In rats, basal lipogenesis, insulin-induced lipogenesis, and insulin sensitivity were two times higher in weaned than in adult animals. Moreover, basal and insulin-induced glucose transport were two times higher in weaned than in adult rats. No differences were detected in GLUT1 or GLUT4 content between any of the age groups in human or in rat adipocytes. In conclusion, basal and insulin-stimulated lipogenesis are increased in adipocytes early in life. This may promote adipose tissue growth in early age. The data indicate that age-dependent variation in basal and insulin-stimulated lipogenesis is differently regulated.

Adipocytes↗

PubMed2003

Animal models for treatment of unresectable liver tumours: a histopathologic and ultra-structural study of cellular toxic changes after electrochemical treatment in rat and dog liver.

INTRODUCTION: Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. MATERIALS AND METHODS: 30 female Sprague-Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. RESULTS: The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose-response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. CONCLUSIONS: The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin.

Animals↗

PubMed2003

Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor.

Primary human hepatocytes were used to elucidate the effect of individual bile acids on bile acid formation in human liver. Hepatocytes were treated with free as well as glycine-conjugated bile acids. Bile acid formation and messenger RNA (mRNA) levels of key enzymes and the nuclear receptor short heterodimer partner (SHP) were measured after 24 hours. Glycochenodeoxycholic acid (GCDCA; 100 micromol/L) significantly decreased formation of cholic acid (CA) to 44% +/- 4% of controls and glycodeoxycholic acid (GDCA) decreased formation of CA to 67% +/- 11% of controls. Glycoursodeoxycholic acid (GUDCA; 100 micromol/L) had no effect. GDCA or glycocholic acid (GCA) had no significant effect on chenodeoxycholic acid (CDCA) synthesis. Free bile acids had a similar effect as glycine-conjugated bile acids. Addition of GCDCA, GDCA, and GCA (100 micromol/L) markedly decreased cholesterol 7alpha-hydroxylase (CYP7A1) mRNA levels to 2% +/- 1%, 2% +/- 1%, and 29% +/- 11% of controls, respectively, whereas GUDCA had no effect. Addition of GDCA and GCDCA (100 micromol/L) significantly decreased sterol 12alpha-hydroxylase (CYP8B1) mRNA levels to 48% +/- 5% and 61% +/- 4% of controls, respectively, whereas GCA and GUDCA had no effect. Addition of GCDCA and GDCA (100 micromol/L) significantly decreased sterol 27-hydroxylase (CYP27A1) mRNA levels to 59% +/- 3% and 60% +/- 7% of controls, respectively, whereas GUDCA and GCA had no significant effect. Addition of both GCDCA and GDCA markedly increased the mRNA levels of SHP to 298% +/- 43% and 273% +/- 30% of controls, respectively. In conclusion, glycine-conjugated and free bile acids suppress bile acid synthesis and mRNA levels of CYP7A1 in the order CDCA > DCA > CA > UDCA. mRNA levels of CYP8B1 and CYP27A1 are suppressed to a much lower degree than CYP7A1.

Adult↗

PubMed2002

Cellular toxicity induced by different pH levels on the R3230AC rat mammary tumour cell line. An in vitro model for investigation of the tumour destructive properties of electrochemical treatment of tumours.

INTRODUCTION: The aim of this study was to evaluate the cellular toxicity of different pH levels on the R3230AC mammary tumour cell line (clone-D) in vitro and to determine in what way the pH affects the tumour cells. The results could be used to interpret the cell damaging effects seen in electrochemical treatment of tumours (EChT), where pH alteration in tissue is the major event. METHODS: Tumour cells were treated with pH 3.5, 5, 7, 9, 10 and 11 for 10, 20 or 30 min, respectively, followed by studies with the viability assay 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyl tetrazolium bromide (methyltetrazolium (MTT)), morphological observation in phase contrast microscope (PCM) and light microscope, nucleotide analogue incorporation (BrdU; 5-Brdmo-2'-deoxyuridine), Caspase-3 activity measurement and detection of DNA fragmentation by an agarose gel electrophoresis. RESULTS: In the viability assay, it was found that different pH levels had cytotoxic effects; these effects were dependent on the pH value and on the time of exposure at a given pH. Morphologically, cells in pH 3.5 and 5 had shrunk, were rounded and had condensed chromatin, whereas prominent cell swelling and nuclear expansion were seen in the pH 9- and 10-treated cells. Gross cytolysis was found in pH 11. A BrdU incorporation assay indicated that proliferation rate is inhibited markedly both with decreasing and increasing pH. Significant Caspase-3 activity was found in pH 3.5 and 5 groups. Caspase-3 levels for the alkaline exposure were equal or below the normal control. DNA ladder formation, a characteristic of apoptosis, was only visualised in the treatment of pH 3.5 for 30 min. CONCLUSIONS: pH changes inhibit cell proliferation and decrease cell viability. The pathway of killing tumour cell in low pH probably has at least two directions: apoptosis and cell necrosis, whereas high pH results in only cell necrosis. The study suggests that low pH environment can induce apoptosis in unphysiological condition comparable with tissue pH at EChT. In addition, it seems that R3230AC mammary tumour cells are more tolerant to high pH than to acidic changes. This supports the theory that anodic EChT should be more efficient than cathodic.

Animals↗

PubMed2002

Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction.

The influence of obesity on the lipolytic capacity of isolated sc fat cells was studied prospectively in 13 women and 10 men, all obese, but otherwise healthy, before and 2 and 3 yr after weight reduction by bariatric surgery. Nonobese subjects (25 women and 17 men) without a family history of obesity served as the control group. Lipolytic capacity was determined after stimulation at different steps of the lipolytic cascade with noradrenaline, isoprenaline, forskolin, and (Bu)(2)AMP. Bariatric surgery was followed by a marked and similar reduction of body mass index and fat cell volume (approximately 40%) in both genders. Before weight loss, lipolytic capacity per cell was elevated in obese women and decreased to normal levels after weight reduction at 2 and 3 yr. However, lipolytic capacity per fat cell surface area was not changed in obese women. In obese men, lipolytic capacity per cell was almost the same as in lean men and was not influenced by weight reduction. Lipolytic capacity was related to fat cell size in women (P = 0.0008; r = 0.58), but not in men (P = 0.67; r = 0.086). The protein content of hormone-sensitive lipase, which determines lipolytic capacity, was significantly lower in obese men and women and increased slightly after weight reduction in men only. Thus, in women, but not in men, the adipocyte lipolytic capacity is influenced by obesity and weight reduction, probably due to changes in fat cell size. These gender differences are not related to the amount of hormone-sensitive lipase protein in adipocytes.

Abdomen↗

PubMed2002

A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance.

The etiology of polycystic ovary syndrome (PCOS) is unknown. However, PCOS has a strong resemblance to the insulin resistance (metabolic) syndrome, where an increased rate of visceral fat cell lipolysis is believed to play a pathophysiological role. We hypothesized that primary defects in visceral lipolysis might also exist in PCOS. Ten young, nonobese, and otherwise healthy PCOS women were compared with 13 matched control women. In vitro lipolysis regulation and stoichiometric properties of the final step in lipolysis activation, namely the protein kinase A (PKA)-hormone sensitive lipase (HSL) complex, were investigated in isolated visceral (i.e., omental) fat cells. Body fat distribution and circulating levels of insulin, glucose, and lipids were normal in PCOS women. However, in vivo insulin sensitivity was slightly decreased (P = 0.03). Catecholamine-induced adipocyte lipolysis was markedly (i.e., about twofold) increased in PCOS women due to changes at the postreceptor level, although there was no change in the antilipolytic properties of visceral fat cells. Western blot analyses of visceral adipose tissue showed twofold increased levels of the catalytic and the regulatory Ialpha components of PKA. In contrast, the regulatory RIIbeta component of PKA was almost 50% decreased in visceral adipose tissue in PCOS women. Recent studies on genetically modified mice have shown that a similar transition in the regulatory PKA units induces an increased lipolytic response to catecholamines. Further analysis showed that the level of HSL-short, an enzymatically inactive splice form of HSL, was decreased in PCOS (P < 0.01). The altered lipolysis in PCOS is different from that observed in visceral fat cells in the insulin resistance syndrome that occurs at the level of adrenergic receptors. We concluded that increased catecholamine-induced lipolysis in visceral fat cells may be due to unique alterations in the stoichiometric properties of the adipose PKA-HSL holoenzymes. This could be an early and possibly primary lipolysis defect in PCOS.

Adipocytes↗

PubMedDate not supplied

Fat oxidation and plasma removal capacity of an intravenous fat emulsion in elderly and young men.

OBJECTIVE: We explored metabolic and thermogenic responses to exogenous fat in relation to age as a basis for a rational design of parenteral nutrition in elderly patients. METHODS: Ten healthy elderly men (70-78 y of age, body mass index 21-27 kg/m(2)) and 10 healthy young men (19-45 y of age, body mass index 19-26 kg/m(2)) were studied with a hypertriglyceridemic clamp (primed infusion of a long-chain triacylglycerol emulsion to reach and stabilize at a triacylglycerol concentration of 4 mmol/L for 180 min). Continuous indirect calorimetry was carried out in the basal state and throughout the study period. RESULTS: The infusion rates required to maintain plasma triacylglycerol levels at 4 mmol/L were similar in elderly and young individuals (mean +/- SEM 0.201 +/- 0.027 versus 0.203 +/- 0.014 mmol/min, not significant). Plasma concentrations of free fatty acids and beta-OH-butyrate were higher in the elderly before the infusion and increased in a similar manner in both groups during infusion. Energy expenditure at baseline was higher in the young than in the elderly (79 +/- 2 versus 64 +/- 3 kcal/h; P < 0.001), although the respiratory quotient was similar in the two groups (0.80 +/- 0.01 versus 0.78 +/- 0.01, not significant). During lipid administration there was a similar increase in energy expenditure in the old and young individuals (+9.0 +/- 1.3% versus +6.0 +/- 1.8%, not significant). Lipid infusion resulted in similar increments in fat oxidation in the young and elderly (23.9 +/- 7.0% versus 15.1 +/- 4.9%, respectively, not significant). Plasma lipoprotein lipase activity was almost three times higher in the young than in the elderly subjects (0.23 +/- 0.02 versus 0.65 +/- 0.09 mU/mL, respectively, P < 0.001). During lipid infusion, a similar increment (four- to five-fold) in plasma lipoprotein lipase activity was noted in the two groups. CONCLUSIONS: Elderly healthy men have a similar capacity as young healthy men to clear and oxidize a high triacylglycerol load administered as a hypertriglyceridemic clamp.

3-Hydroxybutyric Acid↗