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  • 251. Wanjura, Viktor
    et al.
    Lundstrom, Patrik
    Osterberg, Johanna
    Rasmussen, Ib
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sandblom, Gabriel
    Gastrointestinal Quality-of-Life After Cholecystectomy: Indication Predicts Gastrointestinal Symptoms and Abdominal Pain2014In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 12, p. 3075-3081Article in journal (Refereed)
    Abstract [en]

    Despite the fact that cholecystectomy is a common surgical procedure, the impact on long-term gastrointestinal quality of life is not fully known. All surgical procedures for gallstone disease performed at Mora County Hospital, Sweden, between 2 January 2002 and 2 January 2005, were registered on a standard database form. In 2007, all patients under the age of 80 years at follow-up were requested to fill in a form containing the Gastrointestinal Quality-of-Life Index (GIQLI) questionnaire and a number of additional questions. The outcome was analysed with respect to age, gender, smoking, surgical technique, and original indication for cholecystectomy. A total of 627 patients (447 women, 180 men) underwent cholecystectomy, including laparoscopic cholecystectomy (N = 524), laparoscopic cholecystectomy converted to open cholecystectomy (N = 43), and open cholecystectomy (N = 60). The mean time between cholecystectomy and follow-up with the questionnaire was 49 months. The participation rate was 79 %. Using multivariate analysis in the form of generalised linear modelling, the original indication for cholecystectomy in combination with gender (p = 0.0042) was found to predict the GIQLI score. Female gender in combination with biliary colic as indication for cholecystectomy correlated with low GIQLI scores. Female gender also correlated with a higher risk for pain in the right upper abdominal quadrant after cholecystectomy (p = 0.028). We found the original indication for cholecystectomy, together with gender, to predict gastrointestinal symptoms and abdominal pain after cholecystectomy. Careful evaluation of symptoms is important before planning elective cholecystectomy.

  • 252.
    Webb, Dominic-Luc
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Bariatric surgery - time to replace with GLP-1?2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 635-640Article, review/survey (Refereed)
    Abstract [en]

    Obesity with a body mass index (BMI) over 30kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass. Consistent with outcomes of this surgery, GLP-1 suppresses appetite and reduces food intake. This implies that GLP-1 has the potential to achieve a similar therapeutic outcome as gastric bypass. GLP-1 analogs, which are used for the treatment of type 2 diabetes mellitus, also lead to significant weight loss. Altered hormonal profiles after gastric bypass therefore indicate a logical connection between gut peptide hormone levels, weight loss and glucose homeostasis. Furthermore, combinations of GLP-1 with other gut hormones such as peptide YY (PYY) and cholecystokinin (CCK) may be able to reinforce GLP-1 driven reduction in appetite and food intake. Pharmacological intenvention in obesity by use of GLP-1 analogs (exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, taspoglutide) and inhibitors of dipeptidyl peptidase-IV (DPP-IV) degradation that inactivate GLP-1 (sitagliptin, vildagliptin), leading to reduced appetite and weight with positive effects on metabolic control, are realistically achievable. This may be regarded as a low-risk therapeutic alternative to surgery for reducing obesity-related risk factors in the obese with lower BMIs.

  • 253.
    Wegler, Christine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. AstraZeneca R&D, Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, S-43150 Molndal, Sweden..
    Gaugaz, Fabienne Z.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Andersson, Tommy B.
    AstraZeneca R&D, Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, S-43150 Molndal, Sweden..
    Wisniewsk, Jacek R.
    Max Planck Inst Biochem, Dept Prote & Signal Transduct, Biochem Prote Grp, D-82152 Martinsried, Germany..
    Busch, Diana
    Univ Med Greifswald, Dept Clin Pharmacol, Ctr Drug Absorpt & Transport, D-17489 Greifswald, Germany..
    Gröer, Christian
    Univ Med Greifswald, Dept Clin Pharmacol, Ctr Drug Absorpt & Transport, D-17489 Greifswald, Germany..
    Oswald, Stefan
    Univ Med Greifswald, Dept Clin Pharmacol, Ctr Drug Absorpt & Transport, D-17489 Greifswald, Germany..
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Weiss, Frederik
    Univ Tubingen, NMI Nat & Med Sci Inst, D-72770 Reutlingen, Germany..
    Hammer, Helen S.
    Univ Tubingen, NMI Nat & Med Sci Inst, D-72770 Reutlingen, Germany..
    Joos, Thomas O.
    Univ Tubingen, NMI Nat & Med Sci Inst, D-72770 Reutlingen, Germany..
    Poetz, Oliver
    Univ Tubingen, NMI Nat & Med Sci Inst, D-72770 Reutlingen, Germany..
    Achour, Brahim
    Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester M13 9PL, Lancs, England..
    Rostami-Hodjegan, Amin
    Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester M13 9PL, Lancs, England..
    van de Steeg, Evita
    TNO, Netherlands Org Appl Sci Res, NL-3700 AJ Zeist, Netherlands..
    Wortelboer, Heleen M.
    TNO, Netherlands Org Appl Sci Res, NL-3700 AJ Zeist, Netherlands..
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes2017In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 14, no 9, p. 3142-3151Article in journal (Refereed)
    Abstract [en]

    Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically relevant drug transporters and metabolizing enzymes in human liver. Mean protein concentrations were in general quantified to similar levels by methods using whole tissue lysates. Methods using subcellular membrane fractionation gave incomplete enrichment of the proteins. When the enriched proteins were adjusted to levels in whole tissue lysates, they were on average 4 fold lower than those quantified directly in whole tissue lysates. The differences in protein levels were propagated into differences in predictions of hepatic clearance. In conclusion, caution is needed when comparing and applying quantitative proteomics data obtained with different methods, especially since membrane fractionation is common practice for protein quantification used in drug clearance predictions.

  • 254.
    Wegler, Christine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University.
    Matsson, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Krogstad, Veronica
    Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo.
    Urdzik, Jozef
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Christensen, Hege
    Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo.
    Andersson, Tommy B
    DMPK, Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bridging differences in CYP activity between donor-matched human liver microsomes and hepatocytesManuscript (preprint) (Other academic)
  • 255.
    Weiss, Frederik
    et al.
    Univ Tubingen, NMI Nat & Med Sci Inst, Markwiesenstr 55, D-72770 Reutlingen, Germany;SIGNATOPE GmbH, Reutlingen, Germany.
    Hammer, Helen S.
    Univ Tubingen, NMI Nat & Med Sci Inst, Markwiesenstr 55, D-72770 Reutlingen, Germany;SIGNATOPE GmbH, Reutlingen, Germany.
    Klein, Kathrin
    Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany;Univ Tubingen, Dept Clin Pharmacol, Tubingen, Germany.
    Planatscher, Hannes
    Univ Tubingen, NMI Nat & Med Sci Inst, Markwiesenstr 55, D-72770 Reutlingen, Germany;SIGNATOPE GmbH, Reutlingen, Germany.
    Zanger, Ulrich M.
    Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany;Univ Tubingen, Dept Clin Pharmacol, Tubingen, Germany.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wegler, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, Molndal, Sweden.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Joos, Thomas O.
    Univ Tubingen, NMI Nat & Med Sci Inst, Markwiesenstr 55, D-72770 Reutlingen, Germany;SIGNATOPE GmbH, Reutlingen, Germany.
    Poetz, Oliver
    Univ Tubingen, NMI Nat & Med Sci Inst, Markwiesenstr 55, D-72770 Reutlingen, Germany;SIGNATOPE GmbH, Reutlingen, Germany.
    Direct Quantification of Cytochromes P450 and Drug Transporters-A Rapid, Targeted Mass Spectrometry-Based Immunoassay Panel for Tissues and Cell Culture Lysates2018In: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 46, no 4, p. 387-396Article in journal (Refereed)
    Abstract [en]

    The quantification of drug metabolizing enzymes and transporters has recently been revolutionized on the basis of targeted proteomic approaches. Isotope-labeled peptides are used as standards for the quantification of the corresponding proteins in enzymatically fragmented samples. However, hurdles in these approaches are low throughput and tedious sample prefractionation steps prior to mass spectrometry (MS) readout. We have developed an assay platform using sensitive and selective immunoprecipitation coupled with mass spectrometric readout allowing the quantification of proteins directly from whole cell lysates using less than 20,000 cells per analysis. Peptide group-specific antibodies (triple X proteomics antibodies) enable the enrichment of proteotypic peptides sharing a common terminus. These antibodies were employed to establish a MS-based immunoassay panel for the quantification of 14 cytochrome P450 (P450) enzymes and nine transporters. We analyzed the P450 enzyme and transporter levels in genotyped liver tissue homogenates and microsomes, and in samples from a time course induction experiment in human hepatocytes addressing different induction pathways. For the analysis of P450 enzymes and transporters only a minute amount of sample is required and no prefractionation is necessary, thus the assay platform bears the potential to bridge cell culture model experiments and results from whole organ tissue studies.

  • 256.
    Westin, Linn
    et al.
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Wollert, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ljungdahl, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sandblom, Gabriel
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Gunnarsson, Ulf
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Dahlstrand, Ursula
    Karolinska Inst, CLINTEC, Stockholm, Sweden..
    Less Pain 1 Year After Total Extra-peritoneal Repair Compared With Lichtenstein Using Local Anesthesia Data From a Randomized Controlled Clinical Trial2016In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 263, no 2, p. 240-243Article in journal (Refereed)
    Abstract [en]

    Objective:The aim was to compare long-term postoperative pain after inguinal hernia surgery using 2 techniques that have shown favorable long-term outcome in previous randomized studies: Lichtenstein using local anesthesia (LLA) and endoscopic total extra-peritoneal repair (TEP) under general anesthesia.Background:Patients often experience pain after inguinal hernia surgery. These 2 methods in their optimal state have not yet been sufficiently compared.Methods:A randomized controlled trial was conducted to detect any difference in long-term postoperative inguinal pain. Altogether 384 patients were randomized and operated using either TEP under general anesthesia (n=193) or LLA (n=191). One year postoperatively, patients were examined by an independent surgeon and requested to complete the Inguinal Pain Questionnaire (IPQ), a validated questionnaire for the assessment of postoperative inguinal pain.Results:Three hundred seventy-five (97.7%) patients completed follow-up at 1 year. In the TEP group, 39 (20.7%) patients experienced pain, compared with 62 (33.2%) patients in the LLA group (P=0.007). Severe pain was reported by 4 patients in the TEP group and 6 patients in the LLA group (2.1% and 3.2%, respectively, P=0.543). Pain in the operated groin limited the ability to exercise for 5 TEP patients and 14 LLA patients (2.7% and 7.5%, respectively, P=0.034).Conclusions:Patients operated with TEP experienced less long-term postoperative pain and less limitation in their ability to exercise than those operated with LLA. The present data justify recommending TEP as the procedure of choice in the surgical treatment of primary inguinal hernia.

  • 257.
    Westling, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bjurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustavsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Silicone-adjustable gastric banding: disappointing results1998In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 8, no 4, p. 467-474Article in journal (Refereed)
    Abstract [en]

    Background:

    Silicone-adjustable Gastric banding (SAGB) has been popularized as a minimally invasive, completely reversible surgical treatment for morbid obesity. We report here out 3-year experience of SAGB with special reference to complications and side-effects.

    Methods:

    There were 90 patients in total, of whom 72 were women. Median age was 42 (range, 20-68) years and median body mass index (BMI) was 43 (range, 34-57) kg/m2. Laparoscopy was attempted to position the band in 63 cases but had to be converted to laparotomy in 16 (25%). Twenty-seven patients were laparotomized. We used the Swedish band (AB Obtech) throughout the series. In addition to regular clinic visits, patients were followed-up with upper gastrointestinal series 6 months postoperatively and gastroscopy after 2 years or earlier when symptomatic.

    Results:

    Median BMI decreased to 32 kg/m2 after 12 months and to 31 kg/m2 after 24 months. With a median follow-up time of 35 months (range, 22-48), 32 patients (35%) have been re-operated usually with removal of the balloon system and conversion into a Roux-en-Y gastric bypass. The most common reasons for re-operation were band erosion (n = 10) and erosive esophagitis (n = 14). Additional indications for re-operation included pouch dilatation, invagination of distal gastric wall through the band, leakage from the balloon, patient dissatisfaction, and severe allergic reaction. When questioned 2 years postoperatively more than half of the patients reported vomiting, heartburn and regurgitation but 78% still pronounced themselves satisfied with the operation. Esophagitis was found in 56% of the patients at gastroscopy after 2 years.

    Conclusion:

    SAGB could be positioned with laparoscopy in 75% of the cases but the incidence of complications and side-effects postoperatively has been high.

  • 258.
    Westling, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gustavsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Laparoscopic vs open Roux-en-Y gastric bypass: a prospective randomized trial2001In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 11, no 3, p. 284-292Article in journal (Refereed)
    Abstract [en]

    Background:

    The feasibility of laparoscopic Roux-en-Y gastric bypass (Lap-RYGBP) for morbid obesity is well documented. In a prospective randomized trial, we compared laparoscopic and open surgery.

    Methods:

    51 patients (48 females, mean (± SD) age 36 ± 9 years and BMI 42 ± 4 kg/m2) were randomly allocated to either laparoscopy (n=30) or open surgery (n=21). All patients were followed for a minimum of 1 year.

    Results:

    In the laparoscopy group, 7 patients (23%) were converted to open surgery due to various procedural difficulties. In an analysis, with the converted patients excluded, the morphine doses used postoperatively were significantly (p< 0.005) lower in the laparoscopic group compared to the open group. Likewise, postoperative hospital stay was shorter (4 vs 6 days, p<0.025). Six patients in the laparoscopy group had to be re-operated due to Roux-limb obstruction in the mesocolic tunnel within 5 weeks. The weight loss expressed in decrease in mean BMI units after year was 14 and 13 after 1 ± 3 ± 3 laparoscopy and open surgery,respectively (not significant).

    Conclusions:

    Both laparoscopic and open RYGBP are effective and well received surgical procedures in morbid obesity. Reduced postoperative pain, shorter hospital stay and shorter sick-leave are obvious benefits of laparoscopy but conversions and/or reoperations in 1/4 of the patients indicate that Lap-RYGBP at present must be considered an investigational procedure.

  • 259.
    Westling, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Öhrvall, Màrgàretà
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustavsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Roux-en-Y gastric bypass after previous unsuccessful gastric restrictive surgery2002In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 6, no 2, p. 206-211Article in journal (Refereed)
    Abstract [en]

    In the treatment of morbid obesity, simple gastric restrictive methods such as silicone adjustable gastric banding, vertical banded gastroplasty, and nonadjustable gastric banding often fail to control weight in the long run or give rise to intolerable side effects. Here we review our results from conversion of such failures to Roux-en-Y gastric bypass. The study comprised 44 patients (median age 42 years, range 24 to 60 years) who underwent revision surgery in 1996 and 1997. Body mass index at revision was 35 kg/m2 (range 21 to 49 kg/m2). Previous bariatric procedures included silicone adjustable gastric banding (n = 26), vertical banded gastroplasty (n = 13), and gastric banding (n = 5). The most common reasons for conversion after silicone adjustable gastric banding and nonadjustable gastric banding were band erosion (n = 12) and esophagitis (n = 11). Staple line disruption (n = 12) with subsequent weight loss failure was the primary cause after vertical banded gastroplasty. There were no postoperative deaths or anastomotic leaks. One patient underwent reexploration because of an infected hematoma. Reflux symptoms and vomiting resolved promptly. At global assessment 2 years later, 70% of the patients were very satisfied. Median body mass index had decreased to 28 kg/m2 (range 18 to 42 kg/m2). No patient was lost to follow-up. As reported previously, failure after vertical gastric banding can be treated by conversion to Roux-en-Y gastric bypass with good results. In this study we found that failure after silicone adjustable gastric banding can be treated successfully with Roux-en-Y gastric bypass as well.

  • 260.
    Wiemerslage, Lyle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A resting-state fMRI study of obese females between pre- and postprandial states before and after bariatric surgery.2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 45, no 3, p. 333-341Article in journal (Refereed)
    Abstract [en]

    Past studies utilizing resting-state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal-weight controls. However, to what extent bariatric surgery-induced weight loss alters resting-state brain activity in obese humans is less well-studied. Thus, we measured the fractional amplitude of low-frequency fluctuations (fALFF) from eyes-closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m(2) ) in both a pre- and post-prandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting-state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus, and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal, and pre- and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting-state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet. 

  • 261. Willmer, Mikaela
    et al.
    Berglind, Daniel
    Thorell, Anders
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Uddén, Joanna
    Raoof, Mustafa
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Tynelius, Per
    Ghaderi, Ata
    Näslund, Erik
    Rasmussen, Finn
    Changes in BMI and Psychosocial Functioning in Partners of Women Who Undergo Gastric Bypass Surgery for Obesity2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 2, p. 319-324Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There is very little research exploring the effects of Roux-en-Y gastric bypass surgery (RYGB) on the patient's partner. The aim of the present study was to investigate longitudinally whether male partners of female RYGB patients were affected in terms of BMI, sleep quality, body dissatisfaction, depression, and anxiety.

    METHODS:

    Thirty-seven women, with partners who were willing to participate, were recruited from RYGB waiting lists at five Swedish hospitals. Data collection took place during two home visits, 3 months before and 9 months after RYGB surgery. Anthropometrical data were documented, and both women and men completed the Hospital Anxiety and Depression Scale (HADS) and the Karolinska Sleep Questionnaire (KSQ). The men also completed the Male Body Dissatisfaction Scale (MBDS).

    RESULTS:

    The men's BMI changes between the two time points that were analysed using general estimating equation (GEE) regression. Their BMI decreased significantly (β = -0.9, p = 0.004). The change was more pronounced in the 26 men who had a baseline BMI of ≥25 (β = -1.4, p < 0.001). Fixed-effects regression showed a statistically significant association between the men's weight loss and that of the women (β = 0.3, p = 0.004). There were no significant changes in the men's HADS, KSQ, or MBDS scores.

    CONCLUSIONS:

    Overweight/obese male partners of RYGB patients also lose weight during the first 9 months post-operatively. However, symptoms of body dissatisfaction, anxiety, and depression remain unchanged, as does self-reported sleep quality.

  • 262.
    Wisniewski, Jacek R.
    et al.
    Max Planck Inst Biochem, Biochem Prote Grp, Dept Prote & Signal Transduct, Klopferspitz 18, D-82152 Martinsried, Germany..
    Vildhede, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    In-depth quantitative analysis and comparison of the human hepatocyte and hepatoma cell line HepG2 proteomes2016In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 136, p. 234-247Article in journal (Refereed)
    Abstract [en]

    Hepatocytes play a pivotal role in human homeostasis. They are essential in regulation of glucose and lipid levels in blood and play a central role in metabolism of amino acids, lipids, drugs and xenobiotic-compounds. In addition, hepatocytes produce a major portion of proteins circulating in the blood. Hepatocytes were isolated from liver tissue obtained from surgical resections. Proteins were extracted and processed using filter aided sample preparation protocol and were analyzed by LC-MS/MS using high accuracy mass spectrometry. Proteins were quantified by the 'Total Protein Approach' and 'Proteomic Ruler'. We report a comprehensive proteomic analysis of purified human hepatocytes and the human hepatoma cell line HepG2. The complete dataset comprises 9400 proteins and provides a comprehensive and quantitative depiction of the proteomes of hepatocytes and HepG2 cells at the protein titer and copy number dimensions. We describe basic cell organization and in detail energy metabolism pathways and metabolite transport. We provide quantitative insights into protein synthesis and drug and xenobiotics catabolism. Our data delineate differences between the native human hepatocytes and HepG2 cells by providing for the first time quantitative data at protein concentrations and copy numbers. 

  • 263.
    Yamamoto, S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wilczek, H. E.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Groth, C-G.
    Ericzon, Bo-Göran
    Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20-Year Follow-up at a Single Center2010In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 10, no 3, p. 602-611Article in journal (Refereed)
    Abstract [en]

    The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty-four grafts were from donors after cardiac death (DCD) and 16 grafts from heart-beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first-time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post-LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow-up biopsies were performed 18-20 years post-LTx (n = 10) and 6 years post-LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20-year follow-up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool.

  • 264.
    Ölander, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Wisniewski, Jacek
    Max Planck Inst Biochem, Dept Prote & Signal Transduct, Martinsried, Germany..
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    To attach or not to attach: factors behind variable adhesion properties of cryopreserved human hepatocytes2016In: Drug metabolism reviews (Softcover ed.), ISSN 0360-2532, E-ISSN 1097-9883, Vol. 48, p. 103-103Article in journal (Other academic)
  • 265.
    Ölander, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Wiśniewski, Jacek R.
    Max Planck Inst Biochem, Biochem Prote Grp, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany.
    Flörkemeier, Inken
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Handin, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Urdzik, Jozef
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A simple approach for restoration of differentiation and function in cryopreserved human hepatocytes2019In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 93, no 3, p. 819-829Article in journal (Refereed)
    Abstract [en]

    Primary human hepatocytes are used in all facets of liver research, from in vitro studies of xenobiotic disposition and toxicity to the clinical management of liver failure. Unfortunately, cellular stress during isolation and cryopreservation causes a highly unpredictable loss of the ability to attach and form cell-matrix and cell-cell interactions. Reasoning that this problem could be mitigated at the post-thawing stage, we applied label-free quantitative global proteomics to analyze differences between attached and non-attached fractions of cryopreserved human hepatocyte batches. Hepatocytes that were unable to attach to a collagen matrix showed many signs of cellular stress, including a glycolytic phenotype and activation of the heat shock response, ultimately leading to apoptosis activation. Further analysis of the activated stress pathways revealed an increase in early apoptosis immediately post-thawing, which suggested the possibility of stress reversal. Therefore, we transiently treated the cells with compounds aimed at decreasing cellular stress via different mechanisms. Brief exposure to the pan-caspase apoptosis inhibitor Z-VAD-FMK restored attachment ability and promoted a differentiated morphology, as well as formation of 3D spheroids. Further, Z-VAD-FMK treatment restored metabolic and transport functions, with maintained sensitivity to hepatotoxic insults. Altogether, this study shows that differentiation and function of suboptimal human hepatocytes can be restored after cryopreservation, thus markedly increasing the availability of these precious cells.

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