| 1. |
- Jideus, Lena, et al.
(författare)
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Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation
- 2001
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Ingår i: Annals of Thoracic Surgery. - 0003-4975 .- 1552-6259. ; 72:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Background. To evaluate whether thoracic epidural anesthesia (TEA) can reduce the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG).Methods. Forty-one patients undergoing CABG were treated with TEA intraoperatively and postoperatively. Another 80 patients served as the control group. The sympathetic and parasympathetic activities were evaluated by analysis of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively and postoperatively.Results. Postoperative AF occurred in 31.7% of the TEA-treated patients and in 36.3% of the untreated patients (p = 0.77). TEA significantly suppressed sympathetic activity, as indicated by a less pronounced increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients compared to untreated patients. The HRV variable expressing sympathetic activity was significantly lower and the postoperative increase in heart rate was significantly less in the TEA group than in the control group after surgery (p = 0.01, p < 0.001). Among patients developing AF, the maximal number of supraventricular premature beats per minute increased significantly in untreated patients postoperatively but remained unchanged in TEA-treated patients (p = 0.004 versus p = 0.86).Conclusions. TEA has no effect on the incidence of postoperative sustained AF, despite a significant reduction in sympathetic activity.
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| 2. |
- Rhodin, Annica, 1949-
(författare)
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Long-term Effects of Opioids in the Treatment of Chronic Pain : Investigation of Problems and Hazards on Clinical, Biochemical, Cellular and Genetic Levels
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain. The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response. Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation. The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels. The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone. Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.
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| 3. |
- Ahlsson, Fredrik, 1967-, et al.
(författare)
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Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size
- 2013
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 168:1, s. 26-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.STUDY DESIGN:Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.RESULTS:Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.CONCLUSION:The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.
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| 4. |
- Ahlsson, Fredrik, et al.
(författare)
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Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies
- 2010
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 74:4, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Methods: Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed.Results: Median (range) glucose production rate was 805 (653-1,337) mumol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) mumol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Conclusion: Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.
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| 5. |
- Alderman, J. McKee, et al.
(författare)
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Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice
- 2009
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 44:1-2, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Pit1 null (Snell dwarf) and Proph1 null (Ames dwarf) mutant mice lack GH, PRL and TSH. Snell and Ames dwarf mice also exhibit reduced IGF-I, resistance to cancer and a longer lifespan than control mice. Endogenous glucose production during fasting is reduced in Snell dwarf mice compared to fasting control mice. In view of cancer cell dependence on glucose for energy, low endogenous glucose production may provide Snell dwarf mice with resistance to cancer. We investigated whether endogenous glucose production is lower in Snell dwarf mice during feeding. Inhibition of endogenous glucose production by glucose injection was enhanced in 12 to 14 month-old female Snell dwarf mice. Thus, we hypothesize that lower endogenous glucose production during feeding and fasting reduces cancer cell glucose utilization providing Snell dwarf mice with resistance to cancer. The elevation of circulating adiponectin, a hormone produced by adipose tissue, may contribute to the suppression of endogenous glucose production in 12 to 14 month-old Snell dwarf mice. We compared the incidence of cancer at time of death between old Snell dwarf and control mice. Only 18% of old Snell dwarf mice had malignant lesions at the time of death compared to 82% of control mice. The median ages at death for old Snell dwarf and control mice were 33 and 26 months, respectively. By contrast, previous studies showed a high incidence of cancer in old Ames dwarf mice at the time of death. Hence, resistance to cancer in old Snell dwarf mice may be mediated by neuroendocrine factors that reduce glucose utilization besides elevated adiponectin, reduced IGF-I and a lack of GH, PRL and TSH, seen in both Snell and Ames dwarf mice. Proteomics analysis of pituitary secretions from Snell dwarf mice confirmed the absence of GH and PRL, the secretion of ACTH and elevated secretion of Chromogranin B and Secretogranin II. Radioimmune assays confirmed that circulating Chromogranin B and Secretogranin II were elevated in 12 to 14 month-old Snell dwarf mice. In summary, our results in Snell dwarf mice suggest that the pituitary gland and adipose tissue are part of a neuroendocrine loop that lowers the risk of cancer during aging by reducing the availability of glucose.
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| 6. |
- Amcoff, Karin, 1975-, et al.
(författare)
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Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - Oxon, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 52:3, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.
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| 7. |
- Benyamin, Beben, et al.
(författare)
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Identification of novel loci affecting circulating chromogranins and related peptides
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:1, s. 233-242
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Tidskriftsartikel (refereegranskat)abstract
- Chromogranins are pro-hormone secretory proteins released from neuroendocrine cells, with effects on control of blood pressure. We conducted a genome-wide association study for plasma catestatin, the catecholamine release inhibitory peptide derived from chromogranin A (CHGA), and other CHGA- or chromogranin B (CHGB)-related peptides, in 545 US and 1252 Australian subjects. This identified loci on chromosomes 4q35 and 5q34 affecting catestatin concentration (P = 3.40 × 10(-30) for rs4253311 and 1.85 × 10(-19) for rs2731672, respectively). Genes in these regions include the proteolytic enzymes kallikrein (KLKB1) and Factor XII (F12). In chromaffin cells, CHGA and KLKB1 proteins co-localized in catecholamine storage granules. In vitro, kallikrein cleaved recombinant human CHGA to catestatin, verified by mass spectrometry. The peptide identified from this digestion (CHGA360-373) selectively inhibited nicotinic cholinergic stimulated catecholamine release from chromaffin cells. A proteolytic cascade involving kallikrein and Factor XII cleaves chromogranins to active compounds both in vivo and in vitro.
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| 8. |
- Branth, Stefan, et al.
(författare)
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Development of abdominal fat and incipient metabolic syndrome in young healthy men exposed to long-term stress
- 2007
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 17:6, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: The sympathetic nervous system may be involved in the pathophysiology of insulin resistance and metabolic cardiovascular syndrome in young men. The aim was to study the effects of long-term stress on different features of the metabolic syndrome (MES) in formerly non-obese healthy young males during 5 months of defined conditions. METHODS AND RESULTS: Sixteen healthy male sailors (mean age 36.5 (SD)+/-7 years) participating in a sailing race around the world were recruited for the study. Investigations were done before the start and at stop overs after finishing laps 1, 2 and 4 (1, 2(1/2) and 5 months, respectively). Anthropometric and blood pressure data as well as biochemical data associated with MES were substantiated. Food intake and exercise were chartered and largely controlled. A mean weight loss of 4.5+/-2 kg (P<0.005), comprising both fat and lean body mass, was recorded during the first lap. Subsequently after 5 months, a weight gain, mainly consisting of 1.2+/-1.1 kg body fat (P<0.05), took place, concomitantly with a protein mass drop of 0.6+/-1.1 kg (P<0.05). The body fat gain accumulated on the abdominal region. Elevated blood levels of HbA1c, insulin and the triglycerides/high-density lipoprotein ratio were also observed during the race. Likewise heart rate and systolic blood pressure increased slightly but to a statistically significant extent. CONCLUSIONS: Non-obese healthy young men exposed to long-term stress developed abdominal obesity and signs of a metabolic syndrome in embryo, also emphasized by biochemical and blood pressure alterations. It is suggested that long-term and sustained stress activation might be an additional risk factor for the development of MES, even after control of dietary and exercise habits.
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| 9. |
- Branth, Stefan, 1959-
(författare)
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Energy Metabolic Stress Syndrome : Impact of Physical Activity of Different Intensity and Duration
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- All living cell functions require an ongoing supply of energy derived from carbohydrates, lipids and proteins with their own pathways of breakdown. All of them end up in the oxidation of reduced coenzymes, yielding chemically-bound energy in the form of adenosine triphosphate (ATP). One broad definition of energy would be the capability to do work and, therefore, the more work that has to be done, the more energy is needed, which may under extreme conditions put the cell into a state of energy metabolic stress. This complex of problems has been examined in the present thesis, where individuals representing different degrees of training status, have been subjected to various types of stressful work-loads as regards intensity and duration. Meanwhile, the energy turnover has been monitored on different levels as whole body (organism)-, single organ/tissue-, cellular and molecular levels. Combined methodologies have been developed and utilized to examine carefully and in some detail energy expenditure and biochemical variables with study subjects under long-term, (outfield) physically and mentally stressful conditions.When the individuals were in a well-controlled energy balance, a diet rich in saturated fatty acids did not elicit any major metabolic stress signs concerning serum lipoproteins and/or insulin/glucose homeostasis during the test period including high volume and low intensity energy turn over. Only a slight decrease in the Apo-B / Apo-A1 ratio was observed, despite a period of totally sedentary life style among the participants. Mental stress combined with a varying energy balance during off-shore sailing races was shown to cause such an energy metabolic stress situation that development of abdominal obesity and signs of a metabolic syndrome in embryo affected the participants who were young, non-obese men and despite their fairly healthy lifestyle concerning the diet they were on and their physical activity habits. Even well-trained young individuals of both sexes, subjected to exhaustive endurance (high intensity exercise session), developed signs of insulin resistance with a deteriorated intracellular glucose availability leading to a supposed ion pump failure and a disturbed osmoregulation on a cellular level. Hence, they presented themselves as having acquired an energy metabolic stress like condition.In conclusion, an energy metabolic stress syndrome has been described, basically due to impaired fuelling of ion pumps with a cluster of signs and symptoms on single organ/tissue-, cellular and molecular levels manifested by muscular intracellular swelling, tendency towards erythrocyte shrinkage as a consequence of a relative insulin resistance concomitant with ion distribution disturbances (Gardos effect), oxidative stress and osmoregulatory taurine leakage.
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| 10. |
- Branth, Stefan, et al.
(författare)
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Metabolic stress-like condition can be induced by prolonged strenuous exercise in athletes
- 2009
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 114:1, s. 12-25
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have examined energy metabolism during prolonged, strenuous exercise. We wanted therefore to investigate energy metabolic consequences of a prolonged period of continuous strenuous work with very high energy expenditure. Twelve endurance-trained athletes (6 males and 6 females) were recruited. They performed a 7-h bike race on high work-load intensity. Physiological, biochemical, endocrinological, and anthropometric muscular compartment variables were monitored before, during, and after the race. The energy expenditure was high, being 5557 kcal. Work-load intensity (% of VO2 peak) was higher in females (77.7%) than in men (69.9%). Muscular glycogen utilization was pronounced, especially in type I fibres (>90%). Additionally, muscular triglyceride lipolysis was considerably accelerated. Plasma glucose levels were increased concomitantly with an unchanged serum insulin concentration which might reflect an insulin resistance state in addition to proteolytic glyconeogenesis. Increased reactive oxygen species (malondialdehyde (MDA)) were additional signs of metabolic stress. MDA levels correlated with glycogen utilization rate. A relative deficiency of energy substrate on a cellular level was indicated by increased intracellular water of the leg muscle concomitantly with increased extracellular levels of the osmoregulatory amino acid taurine. A kindred nature of a presumed insulin-resistant state with less intracellular availability of glucose for erythrocytes was also indicated by the findings of decreased MCV together with increased MCHC (haemoconcentration) after the race. This strenuous energy-demanding work created a metabolic stress-like condition including signs of insulin resistance and deteriorated intracellular glucose availability leading to compromised fuelling of ion pumps, culminating in a disturbed cellular osmoregulation indicated by taurine efflux and cellular swelling. © 2009 Informa UK Ltd All rights reserved.
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