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Biomedical subjects

Jonas Nygren

Publications and source records attributed to Jonas Nygren.

At least 19 recordsLinked to original sources
PubMed2006

Postoperative parenteral nutrition while proactively minimizing insulin resistance.

OBJECTIVE: We compared the metabolic effects of postoperative total parenteral nutrition (TPN) and hypocaloric glucose after treatment with oral carbohydrates preoperatively and epidural anesthesia to proactively minimize postoperative insulin resistance. METHODS: Thirteen patients undergoing colorectal resections were given oral carbohydrates preoperatively and epidural anesthesia and randomized to TPN or hypocaloric glucose during and after surgery. Insulin sensitivity (hyperinsulinemic clamp [0.8 mU x kg(-1) x min(-1)], normoglycemic clamps [4.5 mM]), and glucose kinetics (6,6(2)H2-D-glucose), were studied before and on postoperative day 3. Indirect calorimetry was performed and nitrogen excretion in urine was measured. Values are presented as mean +/- standard deviation. Analysis of variance, planned comparison, and Bonferroni's correction were used for statistical analysis. RESULTS: Three days after surgery insulin-stimulated whole-body glucose disposal decreased by 24 +/- 11% versus 28 +/- 23% in patients receiving TPN and hypocaloric glucose, respectively (P < 0.05 for both, not significant between groups). Endogenous glucose production during insulin stimulation was increased only in the glucose group after surgery (P < 0.05 versus before). After surgery, insulin-stimulated glucose oxidation was higher after treatment with TPN, whereas fat oxidation was lower (P < 0.05 for both versus glucose treatment). Fat oxidation increased in the glucose group at basal after surgery (P < 0.05 versus before). Nitrogen balance was less negative after treatment with TPN (P < 0.01). CONCLUSIONS: Treatment with TPN does not seem to improve postoperative peripheral insulin sensitivity in patients with minor insulin resistance after pretreatment with preoperative carbohydrates and perioperative epidural anesthesia. Hypocaloric nutrition results in changes in substrate utilization and nitrogen balance resembling starvation, whereas TPN attenuates these changes.

Aged↗
PubMed2006

Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle.

The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased VO2 max by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25-30%) in the concentration of malonyl-CoA were observed after training, 24-36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator-1alpha (PGC-1alpha), a regulator of transcription that has been linked to the mediation of MCD expression by PPARalpha, was also increased (3-fold). In studies also conducted 24-36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1alpha-mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.

AMP-Activated Protein Kinase Kinases↗
PubMed2006

The metabolic effects of fasting and surgery.

This review discusses the metabolic changes that occur during fasting, especially in relation to surgical stress. Currently available evidence on the relevance of different aspects of perioperative nutritional support are presented. Attenuation of surgical stress and insulin treatment in insulin-resistant patients after surgery and trauma have been shown to markedly affect stress metabolism as well as patient morbidity and mortality. Avoiding preoperative fasting has been shown to be related to a substantial reduction in postoperative stress and insulin resistance. Implementation of a standardized programme with a multimodal approach using evidence-based perioperative routines has been shown to further reduce surgical stress and to markedly enhance functional recovery also after major surgical procedures.

Evidence-Based Medicine↗
PubMed2006

Optimizing perioperative management of patients undergoing colorectal surgery: what is new?

PURPOSE OF REVIEW: This review highlights recent developments in individual perioperative interventions in colorectal surgery, and progress in so-called fast-track or enhanced-recovery programmes. RECENT FINDINGS: A new survey from five northern European countries has revealed that best clinical practice in perioperative care, based on previously published high-grade evidence, is only partially in use in daily clinical practice. Recently, a number of trials contrasting clinical results in enhanced-recovery protocols versus traditional care clearly show that such protocols indeed enhance recovery, although effects on morbidity are less obvious. Further evidence supporting preoperative oral carbohydrate treatment, avoidance of oral bowel preparation and wound drainage in elective colonic surgery and avoidance of intraoperative fluid excess has emerged. The oral opioid antagonist alvimopan has recently been shown to limit postoperative gastrointestinal paralysis. The role of laparoscopic surgery in the era of enhanced-recovery programmes is unclear. SUMMARY: There is strong evidence on how to enhance recovery after colorectal surgery, but many interventions are not utilized in daily practice. Further evidence has emerged supporting several perioperative treatments, and successful experiences of enhanced-recovery programmes have now been reported from several centres.

Aged↗
PubMed2006

Combined treatment with exercise training and acarbose improves metabolic control and cardiovascular risk factor profile in subjects with mild type 2 diabetes.

OBJECTIVE: The effect of exercise training and acarbose on glycemic control, insulin sensitivity, and phenotype was investigated in mild type 2 diabetes. RESEARCH DESIGN AND METHODS: Sixty-two men and women with type 2 diabetes were randomized to 12 weeks of structured exercise training with or without acarbose treatment or to acarbose alone. Glycemic control was determined by HbA(1c) (A1C), insulin sensitivity (M value) by euglycemic-hyperinsulinemic clamp, and regional fat distribution by computerized tomography and dual X-ray absorptiometry. Physical fitness was determined as maximal oxygen uptake (Vo(2max)). All investigations were performed before and after the intervention. RESULTS: Forty-eight subjects completed the study. Exercise improved M value by 92% (P = 0.017) and decreased total and truncal fat (P = 0.002, 0.001) and systolic blood pressure (P = 0.01) but had no significant effect on Vo(2max) or A1C level. The combination of exercise and acarbose significantly decreased fasting plasma glucose, A1C, lipids, and diastolic blood pressure and increased Vo(2max), whereas effects on M value and body composition were comparable with that of exercise alone. Acarbose alone had no significant effect on either M value or A1C but decreased systolic (P = 0.001) and diastolic blood pressure (P = 0.001) and fasting proinsulin level (P = 0.009). Multiple regression analysis showed that addition of acarbose to exercise improved glycemic control. CONCLUSIONS: In subjects with mild type 2 diabetes, exercise training improved insulin sensitivity but had no effect on glycemic control. The addition of acarbose to exercise, however, was associated with significant improvement of glycemic control and possibly cardiovascular risk factors.

Acarbose↗
PubMed2005

Nutritional support and oral intake after gastric resection in five northern European countries.

BACKGROUND: A comprehensive evidence base for perioperative care in upper gastrointestinal (GI) surgery is lacking. Little is known about the routines currently practiced in the absence of such evidence. We describe postoperative practice after gastric resections in five northern European countries. METHOD AND SETTING: Questionnaire survey in all major digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway. RESULTS: 76% of all centres (n = 200/263) responded. Routines varied extensively both nationally and between countries. No uniformity was traced although a conservative trend was noticeable in the use of nasogastric decompression tubes and 'nil-by-mouth' regimens. Nutritional support during the first 5 days is generally offered in Denmark, but not in Scotland. Drinking at will is generally allowed in Denmark and Norway by the first postoperative day. Eating at will is uniformly restricted. CONCLUSION: The paucity of evidence is reflected by the marked heterogeneity in practice. Large groups of patients may be treated suboptimally. Best perioperative care for these patients must be defined and documented. Especially, the role of early oral intake at will in upper GI surgery needs to be clarified by sufficiently powered trials.

Denmark↗
PubMed2005

A comparison in five European Centres of case mix, clinical management and outcomes following either conventional or fast-track perioperative care in colorectal surgery.

BACKGROUND & AIMS: This study reviewed the case mix, clinical management, and clinical outcomes of patients undergoing colorectal resection in five European centres performing different forms of conventional or 'fast-track' perioperative care. METHODS: The perioperative care programme and surgical practice in each centre was defined. Patient data were collected by case-note review on an internet-based audit system. Case mix was determined using ASA classification and the P-POSSUM scoring system. RESULTS: A total of 451 consecutive patients from units practicing either conventional (Sweden, n=109; UK, n=87; Netherlands, n=76, Norway, n=61) or fast-track surgery (Denmark, n=118), were studied between 1998 and 2001. Elements of perioperative practice varied widely both between units practicing 'traditional' care and the reference 'fast-track' unit (Denmark). Based on the P-POSSUM scores, the case mix was similar between centres. There were no differences in morbidity or 30-day mortality between the different centres. The median length of stay was 2 days in Denmark and 7-9 days in the other centres (P<0.05). The readmission rate was 22% in Denmark and 2-16% in the other centres (P<0.05). CONCLUSION: Compared with traditional care, fast-track perioperative care results in a reduced length of hospital stay but may be associated with a higher readmission rate. Morbidity and mortality appears to be similar with either approach. Prospective evaluation of the potential benefits of the fast-track approach in different European centres is merited.

Aged↗
PubMed2005

Functional and physiologic assessment of the colonic reservoir or side-to-end anastomosis after low anterior resection for rectal cancer: a two-year follow-up.

PURPOSE: Functional disturbances are common after anterior resection for rectal cancer. This study was designed to compare functional and physiologic outcome after low anterior resection and total mesorectal excision with a colonic J-pouch or a side-to-end anastomosis. METHODS: Functional and physiologic variables were analyzed in patients randomized to a J-pouch (n = 36) or side-to-end anastomosis (n = 35). Postoperative functional outcome was investigated with questionnaires. Anorectal manometry was performed preoperatively and at six months, one year, and two years postoperatively. RESULTS: There was no statistical difference in functional outcome between groups at two years. Maximum neorectal volume increased in both groups but was approximately 40 percent greater at two years in pouches compared with the side-to-end anastomosis. Anal sphincter pressures volumes were halved postoperatively and did not recover during follow-up of two years. Male gender, low anastomotic level, pelvic sepsis, and the postoperative decrease of sphincter pressures were independent factors for more incontinence symptoms. CONCLUSIONS: Colonic J-pouch and side-to-end anastomosis gives comparable functional results two years after low anterior resection. Neorectal volume had no detectable influence on function. There was a pronounced and sustained postoperative decrease in sphincter pressures.

Adult↗
PubMed2005

Effect of "preoperative" oral carbohydrate treatment on insulin action--a randomised cross-over unblinded study in healthy subjects.

BACKGROUND AND AIMS: Preoperative intake of a clear carbohydrate-rich drink reduces insulin resistance after surgery. In this study, we evaluated whether this could be related to increased insulin sensitivity at the onset of surgery. Furthermore, we aimed to establish the optimal dose-regimen. METHODS: Six healthy volunteers underwent hyperinsulinaemic (0.8 mU/kg/min), normoglycaemic (4.5 mmol/l) clamps and indirect calorimetry on four occasions in a crossover-randomised order; after overnight fasting (CC), after a single evening dose (800 ml) of the drink (LC), after a single morning dose (400 ml, CL) and after intake of the drink in the evening and in the morning before the clamp (LL). Data are presented as mean+/-SD. Statistical analysis was performed using the Student's t-test and ANOVA. RESULTS: Insulin sensitivity was higher in CL and LL (9.2+/-1.5 and 9.3+/-1.9 mg/kg/min, respectively) compared to CC and LC (6.1+/-1.6 and 6.6+/-1.9 mg/kg/min, P<0.01 vs. CL and LL). CONCLUSIONS: A carbohydrate-rich drink enhances insulin action 3 h later by approximately 50%. Enhanced insulin action to normal postprandial day-time level at the time of onset of anaesthesia or surgery is likely to, at least partly, explain the effects on postoperative insulin resistance.

Administration, Oral↗
PubMed2005

Oxidative DNA damage in cultured fibroblasts from patients with hereditary glutathione synthetase deficiency.

The SH compound glutathione (GSH) is involved in several fundamental functions in the cell, including protection against reactive oxygen species (ROS). Here, we studied the effect on oxidative DNA damage in cultured skin fibroblasts from patients with hereditary GSH synthetase deficiency. Our hypothesis was that GSH-deficient cells are more prone to DNA damage than control cells. Single cell gel electrophoresis (the comet assay) in combination with the formamidopyrimidine DNA glycosylase enzyme, which recognizes oxidative base modifications, was used on cultured fibroblasts from 11 patients with GSH synthetase deficiency and five control subjects. Contrary to this hypothesis, we found no significant difference in background levels of DNA damage between cells from patients and control subjects. To study the induction of oxidative DNA damage without simultaneous DNA repair, the cells were gamma-irradiated on ice and DNA single-strand breaks measured. The patient and control cells were equally sensitive to induction of single strand breaks by gamma-irradiation. Therefore, factors other than GSH protect DNA from oxidative damage. However, cells with a high background level of oxidative DNA damage were found to be more sensitive to ionizing radiation. This suggests that differences in background levels of oxidative DNA damage may depend on the cells' intrinsic protection against induction of oxidative damage.

Adolescent↗
PubMed2005

Metabolic perioperative management: novel concepts.

PURPOSE OF REVIEW: This review summarizes novel information regarding the role of metabolic control in the perioperative period. RECENT FINDINGS: Managing perioperative metabolism has recently been shown to be an important way to improve outcomes in surgical care. In particular, postoperative insulin resistance and hyperglycemia have been linked to many common complications. Recent studies have explored the toxicity of hyperglycemia and suggest a causal relation between insulin resistance and complications in the postoperative state. Controlling glucose concentrations with insulin has been shown to also improve protein balance and fat metabolism. In addition, insulin may affect other hormones including insulinlike growth factor-I during surgical stress. Lastly, recent data suggest that hyperglycemia plays an important role in aggravating the inflammatory response, in that overflow of substrates in the mitochondria causes the formation of excess free oxygen radicals and may also alter gene expression to enhance cytokine production. Although overcoming insulin resistance by insulin infusion is one way of combating hyperglycemia, prevention of its development can also be achieved by using epidural blockade to reduce the release of adrenal stress hormones and to control pain, by preoperative carbohydrates instead of overnight fasting, and by minimal invasive surgical techniques. SUMMARY: Minimizing the effects of insulin resistance has been shown to substantially improve outcome after surgical stress.

Diabetes Mellitus↗
PubMed2004

Genotoxicity of airborne particulate matter: the role of cell-particle interaction and of substances with adduct-forming and oxidizing capacity.

Exposure to particulate matter (PM) is associated with several health effects including lung cancer. However, the mechanisms of particle-induced carcinogenesis are not fully understood. The main aim of this study was to investigate the genotoxicity of PM in relation to particle-cell interactions and to study the effect of removal of DNA-damaging substances by extraction of PM with different solvents. Genotoxicity was analyzed by means of the comet assay after exposure of cultured human fibroblasts to urban dust particles (SRM 1649). It was found that PM induced DNA damage in a dose-dependent manner and that cells interacting with PM suffered more DNA single-strand breaks relative to other cells. The genotoxicity of PM was significantly reduced after extraction with dichloromethane (DCM), dimethyl sulfoxide (DMSO) and water, but not with acetone and hexane. However, the insoluble particle core still induced DNA single-strand breaks. The extracts were further investigated in cell-free systems. Analysis of aromatic DNA adducts with 32P-HPLC showed that the DMSO and DCM extracts contained most of the DNA-reactive polyaromatic compounds (PACs). Further, the formation of 8-oxo-2'-deoxyguanosine (8-oxodG) upon incubation of the extracts with 2'-deoxyguanosine (dG) showed that the water extract contained most of the oxidizing substances. Thus, the genotoxicity of PM was caused both by adduct-forming PACs and oxidizing substances as well as the insoluble particle-core. This study showed that all these factors together contribute to explaining the mechanisms of PM genotoxicity.

Air Pollutants↗
PubMed2004

Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks.

The protein kinase ataxia telangiectasia mutated (ATM) is activated when cells are exposed to ionizing radiation (IR). It has been assumed that ATM is specifically activated by the few induced DNA double strand breaks (DSBs), although little direct evidence for this assumption has been presented. DSBs constitute only a few percent of the IR-induced DNA damage, whereas the more frequent single strand DNA breaks (SSBs) and base damage account for over 98% of the overall DNA damage. It is therefore unclear whether DSBs are the only IR-induced DNA lesions that activate ATM. To test directly whether or not DSBs are responsible for ATM activation, we exposed cells to drugs and radiation that produce different numbers of DSBs and SSBs. We determined the resulting ATM activation by measuring the amount of phosphorylated Chk2 and the numbers of SSBs and DSBs in the same cells after short incubation periods. We found a strong correlation between the number of DSBs and ATM activation but no correlation with the number of SSBs. In fact, hydrogen peroxide, which, similar to IR, induces DNA damage through hydroxyl radicals but fails to induce DSBs, did not activate ATM. In contrast, we found that calicheamicin-induced strand breaks activated ATM more efficiently than IR and that ATM activation correlated with the relative DSB induction by these agents. Our data indicate that ATM is specifically activated by IR-induced DSBs, with little or no contribution from SSBs and other types of DNA damage. These findings have implications for how ATM might recognize DSBs in cells.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2004

DNA damage in bronchial epithelial and mesothelial cells with and without associated crocidolite asbestos fibers.

Mesothelioma is induced almost exclusively by exposure to asbestos fibers. We have investigated whether the induction of DNA damage in human bronchial epithelial BEAS 2B cells and human mesothelial MeT 5A cells by crocidolite asbestos (2 microg/cm2) requires the presence of asbestos fibers in the cells. DNA damage was measured microscopically by the Comet assay, and the presence of fibers in the same cells was assessed using bright-field illumination. After treatment times of 6-72 hr, damage levels were, on the average, two times higher in cells with fibers than in cells without fibers. It was further found that DNA damage decreased with time in BEAS 2B cells both with and without fibers. No decrease in damage with time was seen in MeT 5A cells, suggesting that these mesothelial cells repair the initial damage poorly, lack induction of protective systems, or constantly produce high levels of damaging species. Our results indicate that crocidolite-treated human mesothelial MeT 5A and bronchial epithelial BEAS 2B cells show an elevated level of DNA damage if they contain a fiber. In comparison with epithelial BEAS 2B cells, mesothelial MeT 5A cells have more DNA damage after the crocidolite treatment and the damage is more persistent.

Apoptosis↗
PubMed2004

Preoperative oral carbohydrate treatment attenuates endogenous glucose release 3 days after surgery.

BACKGROUND & AIMS: Postoperative metabolism is characterised by insulin resistance and a negative whole-body nitrogen balance. Preoperative carbohydrate treatment reduces insulin resistance in the first day after surgery. We hypothesised that preoperative oral carbohydrate treatment attenuates insulin resistance and improves whole-body nitrogen balance 3 days after surgery. METHODS: Fourteen patients undergoing total hip replacement were double-blindly randomised to preoperative oral carbohydrate treatment (12.5%, 800 + 400 ml, n = 8) or placebo (n = 6). Glucose kinetics (6,6-D2-glucose), substrate utilisation (indirect calorimetry) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured preoperatively and on the third day after surgery. Nitrogen losses were monitored for 3 days after surgery. Values are mean (SEM). Analysis of variance (ANOVA) statistics were used. RESULTS: Endogenous glucose release during insulin infusion increased after surgery in the placebo group. Preoperative carbohydrate treatment, as compared to placebo, significantly attenuated postoperative endogenous glucose release (0.69 (0.07) vs. 1.21 (0.13)mg kg(-1) x min(-1), P < 0.01), while whole-body glucose disposal and nitrogen balance were similar between groups. CONCLUSIONS: While insulin resistance in the first day after surgery has previously been characterised by reduced glucose disposal, enhanced endogenous glucose release was the main component of postoperative insulin resistance on the third postoperative day. Preoperative carbohydrate treatment attenuated endogenous glucose release on the third postoperative day.

Administration, Oral↗
PubMed2004

Insulin stimulated glucose disposal in peripheral tissues studied with microdialysis and stable isotope tracers.

BACKGROUND & AIMS: Methods to study glucose kinetics in vivo in specific tissues or tissue beds in humans are often not feasible due to invasiveness or costs of equipment needed. Here we investigate whether the loss (fractional extraction) of 2H7-glucose infused via a microdialysis catheter can be used to study glucose disposal in skeletal muscle and subcutaneous adipose tissue. METHODS AND RESULTS: A perfusion period of 2 h was needed to ensure an isotopic steady state in the microdialysis catheters in skeletal muscle and adipose tissue. In six healthy volunteers the fractional extraction increased during a hyperinsulinemic euglycemic clamp in both skeletal muscle and adipose tissue. Following 48 h of starvation in the same subjects, insulin was not able to increase the fractional extraction of 2H7-glucose from the microdialysis in comparison with a baseline measurement. CONCLUSIONS: In response to insulin infusion, the fractional extraction of 2H7-glucose from a microdialysis catheter increases in skeletal muscle and subcutaneous adipose tissue and this increase is blunted during insulin resistance induced by starvation. These results validate that the fractional extraction of a glucose tracers infused via microdialysis can be used as an index of glucose disposal in peripheral tissues or tissue beds.

Adipose Tissue↗
PubMed2004

Microdialysis methods for measuring human metabolism.

PURPOSE OF REVIEW: To discuss the advantages and limitations of the microdialysis technique as a diagnostic and research tool using recent findings on human metabolism. RECENT FINDINGS: Results from several studies have supported the potential of microdialysis as a diagnostic tool for metabolic monitoring in difficult accessible tissues (brain, liver, intestine). However, despite promising results, no clear diagnostic measures have yet emerged. Several studies combining microdialysis with stable isotope tracers have shown that this approach has great potential for studying human metabolism non-invasively in specific tissue beds in a more dynamic way. SUMMARY: Bearing in mind the limitations and assumptions, the microdialysis technique is a useful tool in investigations of human metabolism. Its main advantages are that it can be used safely with low-grade invasiveness in humans, and thereby allows continuous sampling over prolonged periods of time from specific tissues without taking any biopsies. At present, microdialysis would seem to be useful as a diagnostic tool when integrated in the total clinical, physiological and pharmacological evaluation. Within human metabolic research, microdialysis has been and will be a very useful technique.

Brain↗