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Biomedical subjects

C Carlsson

Publications and source records attributed to C Carlsson.

At least 19 recordsLinked to original sources

Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells.

Pancreatic beta-cells have low activities of the antioxidant enzyme catalase. Nitric oxide interacts with the haem group of catalase inhibiting its activity. We have studied the activity of catalase in beta-cells under conditions mimicking prediabetes and in which nitric oxide is generated from cytokine treatment in vitro. We also studied whether there is regulation of catalase enzyme activity by nitric oxide at the protein or gene expression level. RINm5F insulin-producing cells, treated for 24 h with cytokines, showed increased medium nitrite production (17+/-2.2 vs 0.3+/-0.2 pmol/ micro g protein) and significantly decreased cellular catalase activity (42.4+/-4.5%) compared with control cells. A similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or human pancreatic islets of Langerhans. Catalase activity was also suppressed by the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta-NO) and this inhibition was reversible. The inhibition of catalase activity by cytokines in RINm5F cells was significantly reversed by the addition of the nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3-(aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be unchanged in cytokine- or Deta-NO-treated RINm5F cells, while mRNA expression was marginally increased. We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine- or nitric oxide-induced cell killing.

Amidines↗

Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells: possible physiological implications.

Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ovaries. We have previously cloned Pref-1 from neonatal rat islets stimulated by GH. The aim of the present study was to elucidate the biosynthesis and release of Pref-1/FA1 in beta-cells and to determine if Pref-1/FA1 is mediating the mitogenic effect of GH in insulin-producing cells. First we studied the biosynthesis and processing of Pref-1 to the soluble form, FA1, in pancreatic islets and insulinoma cells transfected with Pref-1 cDNA. We measured the release of FA1 by ELISA and the possible effect of FA1 in GH-stimulated beta-cell proliferation by incorporation of bromodeoxyuridine (BrdU) in insulin-positive islet cells. We found that Pref-1 was synthesized in normal islets and in RINm5F insulinoma cells and released into the medium in two forms, of which one corresponded to FA1. Both the expression of the mRNA for Pref-1 and the release of the soluble form(s) were stimulated by GH and prolactin (PRL). Whereas 2 h exposure to high glucose or 3-isobutyl-1-methylxanthine stimulated insulin release, only a small change was seen in FA1 release, suggesting that the FA1 is released by a different pathway than insulin. However, long-term exposure (48 h) to high glucose increased FA1 secretion, indicating that FA1 is regulated by glucose. Neither FA1 nor conditioned medium from GH-stimulated islets depleted for GH was able to increase beta-cell replication and overexpression of Pref-1 resulted in attenuated proliferation of the RINm5F cells. By immunocytochemistry of GH-stimulated islet cells no correlation between high Pref-1 expression and BrdU incorporation was observed and there was an inverse relationship between the levels of insulin and Pref-1. These results indicate that Pref-1/FA1 is not mediating the mitogenic effect of GH and PRL. Therefore the function of Pref-1 in the beta-cell remains unknown.

1-Methyl-3-isobutylxanthine↗

[Simulator training in medicine and health care. A new pedagogic model for good patient safety].

Advanced simulation within medicine and health care is a rapidly growing field. Simulator based training can be applied in minimal invasive surgery, in endoscopic procedures as well as in anaesthesia and critical care management. At Huddinge University Hospital a center for advanced simulation of both endoscopic surgery and anaesthesia/critical care management is currently being set up. The objective is to focus on improved medical and health care training and thus improving patient safety by reducing medical errors.

Anesthesiology↗

Contribution of suspended and sorbed groundwater bacteria to degradation of dissolved and sorbed aniline.

The influence of sorption on the mineralisation of 50 pg aniline l(-1) was examined in an aquifer material under batch conditions. The study was designed to distinguish the rates and extent of biodegradation of the sorbed and the dissolved trace organic and the contribution of sorbed and suspended bacteria to the degradation. Four different mathematical models were developed with different assumptions about the partitioning of aniline degradation and bacterial activity between the solid and the aqueous phases. The models were developed by combining an expression for logistic growth of the degrading population with Michaelis-Menten kinetics for the transformation of aniline. It was tested by a series of laboratory experiments conducted with 14C-labelled aniline, aseptically treated aquifer sand and filter-sterilised groundwater in different proportions and bacteria isolated from pristine groundwater. Model evaluation of the experimental data suggested that the fate of aniline was mainly controlled by suspended bacteria degrading both the dissolved and sorbed fractions. The degradation was slow, with a first-order degradation rate equal to 10(-6) h(-1).

Aniline Compounds↗

Voluntary associations for cancer patients in Sweden: supportive activities.

Our aim was to describe voluntary associations for patients with cancer in Sweden (n=108) and their activities, type and extent of member support, and the associations' collaboration with the health care system. A specially constructed questionnaire with structured and open questions was used for the investigation. The frequency of answers was 89%. The results show in the broadest sense that the associations have two missions. The direct patient-related mission concerns providing patients with support in the form of close proximity, approachability and through distribution of knowledge together with financial and practical support; the indirect patient-related mission deals with activities aimed at improving conditions for patients in general within the health care system and by influencing authorities as well as supporting family members and significant others and providing financing. The associations collaborate with the health care system, although they face difficulties in becoming 'sanctioned' and in establishing positive relationships with the health care community. The associations display a positive attitude towards their cause and the personal gratification that the voluntary work brings. In general, the findings indicate that the associations have a potential to help patients live and cope with their cancer disease.

Health Care Coalitions↗

7-Ethoxyresorufin O-deethylase induction in rainbow trout gill epithelium cultured on permeable supports: asymmetrical distribution of substrate metabolites.

The induction of 7-ethoxyresorufin O-deethylase (EROD) has been measured in cultured epithelia from rainbow trout gills. Epithelia incubated with water on the apical side and culture media at the basolateral side were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (betaNF), benzo[k]fluoranthene (B(k)F), and 3,3',4,4',5-pentachlorobiphenyl (PCB#126) from the water. EROD activity was measured as the formation of resorufin from 7-ethoxyresorufin over time in intact epithelia. The EC(50) values obtained after 24 h of exposure (mean+/-S.D.) were for TCDD (n=9) 4.1+/-3.2x10(-11) M, for betaNF (n=6) 1.6+/-3.8x10(-9) M, for B(k)F (n=4) 5.4+/-3.0x10(-9) M and for PCB#126 (n=4) 6.15+/-10.1x10(-9) M. When assaying for EROD activity, it was found that the resorufin concentrations differed between the apical and the basolateral compartments, indicating an asymmetrical distribution of the enzymatically formed resorufin molecules. Generally, the resorufin concentration was highest in the basolateral compartment, but there were differences between epithelia obtained from different fish individuals. Of a total of 13 preparations 10 had the highest resorufin concentration in the basolateral compartment, while in three preparations, the resorufin was uniformly distributed or slightly higher in the apical compartment. The reasons for this asymmetrical distribution of substrate metabolites are not known, and the addition of multidrug resistance inhibitors (verapamil and cyclosporin A) did not alter the asymmetrical pattern. The transepithelial electrical resistance (TER) was also measured to diagnose the tightness of the epithelia. The change from culture media to experimental water (containing TCDD, betaNF, or DMSO as control) in the apical compartment resulted in a large increase in TER, followed by a decline, measured after 24 h. The cytochrome P450 1A (CYP1A) inducers had no effect on the TER and were judged, therefore, not to affect the tightness of the epithelia.

Animals↗

Degradation of dissolved and sorbed 2,4-dichlorophenol in soil columns by suspended and sorbed bacteria.

The influence of sorption of bacteria, as well as 2,4-dichlorophenol (2,4-DCP), on the mineralization of 100 microg l(-1) of the organic compound was examined in an aquifer material under advective flow conditions (column displacement technique). The study was designed to distinguish the rates and extent of biodegradation of the sorbed and the dissolved trace organic and the contribution of sorbed and suspended bacteria to the degradation. The degradation of dissolved 2,4-DCP was significantly faster than the degradation of the same compound sorbed to the solids, and suspended bacteria degraded the dissolved compound at a higher rate than sorbed bacteria, also on a per cell basis. The suspended bacteria degraded 8-12% of the added dissolved 2.4-DCP, while sorbed bacteria made a smaller contribution by degrading about 5% of sorbed 2,4-DCP. No degradation was seen with sorbed 2,4-DCP and suspended bacteria, and a marginal contribution was made by sorbed bacteria on the degradation of dissolved 2,4-DCP (<0.4%).

Bacteria↗

A single-injection, multi-segmental paravertebral block-extension of somatosensory and sympathetic block in volunteers.

BACKGROUND: It is our experience that a deposition of an anesthetic solution in the ventral area of the paravertebral space near the parietal pleura and the sympathetic trunk produces extended unilateral block. Because sympathetic block effects in this extended paravertebral block are not reported yet, we undertook this singly blinded, controlled study on the sympathetic change in volunteers. METHODS: A total of 22 ml 1% lidocaine was injected at the T11 level into the ventral area of the right-sided paravertebral space in 16 volunteers. The distribution of analgesia, heart rate, blood pressure and body temperature (measured by 12 skin sensors) was monitored. On a later occasion the volunteers underwent a control injection of saline. RESULTS: Unilateral analgesia (with no contralateral element) was induced in every subject injected with lidocaine, contrasted with no block induction with saline. Loss of pin-prick sensation was observed within 10 min after injection and involved a mean of 12 (range 8-13) dermatomes. A sympathetic block was indicated by cutaneous temperature increase within at least 6 dermatomes. Increase of arterial blood pressure was obtained in all volunteers with no change in pulse rate. No side effects or complications occurred. Epidural spread of the local anesthetic was unlikely because of the absence of contralateral cutaneous analgesia and temperature increase. CONCLUSION: One-sided extended analgesia (sensory loss) follows the paravertebral injection of lidocaine. A large ipsilateral sympathetic block is observed without change in pulse rate and with no hypotension. These are all characteristics of an optimal regional block.

Adult↗

Effects of stretch or distention on phenylephrine-induced constriction of human coronary artery bypass grafts.

OBJECTIVE: To determine the effects of grafting saphenous veins into the arterial circulation and to compare the responsiveness of saphenous veins and mammary arteries to vasoconstrictors (phenylephrine or potassium) and a vasodilator (the calcium antagonist isradipine). DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins obtained from patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue chambers. The law of LaPlace for a cylinder was applied to determine tensions in vitro corresponding with arterial or venous tensions in vivo or distending pressures ex vivo. MEASUREMENTS AND MAIN RESULTS: Stretching saphenous vein rings from venous to arterial tensions reduced maximal phenylephrine-induced constriction but did not alter their dose response to phenylephrine, potassium, or isradipine. At arterial tensions, potassium, but not phenylephrine, was more potent in constricting mammary artery than saphenous vein; isradipine was more potent as a vasodilator of potassium-constricted mammary artery than saphenous vein. Maximal phenylephrine-induced or potassium-induced constriction was no different for either vessel at arterial tensions; however, prior distention of veins to tensions corresponding with pressures of 200 or 300 mmHg significantly (p < 0.01, Dunnett's test) reduced subsequent constriction. CONCLUSION: Phenylephrine may be more likely to constrict native internal mammary arteries than distended autogenous saphenous vein grafts in vivo because high-pressure distention of veins markedly inhibits their vasoreactivity.

Coronary Artery Bypass↗

Regulation of beta-cell mass by hormones and growth factors.

Substantial new information has accumulated on molecular mechanisms of pancreas development, regulation of beta-cell gene expression, and the role of growth factors in the differentiation, growth, and regeneration of beta-cells. The present review focuses on some recent studies on the mechanism of action of cytokines such as growth hormone (GH) and prolactin (PRL) in beta-cell proliferation and gene expression-in particular, the role of signal transducers and activators of transcription (STAT) proteins. The implication of the discovery of suppressors of cytokine signaling (SOCS) proteins for the interaction between stimulatory and inhibitory cytokines, including GH, PRL, leptin, and the proinflammatory cytokines interleukin-1 and interferon-gamma, in beta-cell survival is not yet clear. Recent studies indicate a role of cell adhesion molecules and the delta-like protein preadipocyte factor 1/fetal antigen 1 (Pref-1/FA-1) in cytokine-induced beta-cell growth and development. Surprisingly, glucagon-like peptide-1 (GLP-1) was recently found to stimulate not only insulin secretion but also beta-cell replication and differentiation, which may present a new perspective in treatment of type 2 diabetes. Together with the intriguing reports on positive effects of insulin on both beta-cell growth and function, a picture is emerging of an integrated network of signaling events acting in concert to control beta-cell mass adaptation to insulin demand.

Animals↗

Xenobiotic and steroid biotransformation activities in rainbow trout gill epithelial cells in culture.

The biotransformation of xenobiotics and steroids was investigated in cultured respiratory epithelial cells from rainbow trout (Oncorhynchus mykiss) gills. As a first approach, ethoxyresorufin-O-deethylase (EROD), chosen as a marker of CYP1A activity, was measured in monolayers of adherent cells. The induction of this enzyme was studied in cells exposed to beta-naphthoflavone (BNF) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in concentrations ranging from 10(-6) to 10(-12) M. After 24 h, TCDD showed a maximal induction at a concentration of 10(-9) M while BNF showed a maximal induction at a concentration of 10(-7) M. Concurrently, a variety of substrates involved in cytochrome P450-dependent metabolism as well as phase II reactions, namely ethoxycoumarin, aniline and testosterone were incubated with cultured gill cells for 2 or 8 h and with freshly isolated hepatocytes for comparison. Our results revealed a significant cytochrome P450-dependent activity in gill cells with ethoxycoumarin and aniline, but no hydroxylation was observed with testosterone as substrate. No trace of sulfate conjugate was detected. With 2.5 µM aniline as substrate, 2-hydroxyaniline accounted for 32.1% of the radioactivity after 2 h incubation whereas acetanilide amounted to 6.4%. Significant differences were found between gill cells and isolated hepatocytes in the capacity of these systems to conduct oxidative and conjugating metabolic pathways. Qualitatively, the main difference was observed for testosterone which is hydroxylated in position 6beta and 16beta and conjugated to glucuronic acid in liver cells, whereas reductive biotransformation giving rise to dihydrotestosterone and androstanediol and traces of androstenedione were observed in gill cells. Quantitatively, the biotransformation activity in gill epithelial cells, expressed as pmol/h per mg protein, was between 1.5 and 14% of the activity level observed in isolated hepatocytes, depending on the substrate.

Journal Article↗

Effects of oxytocin treatment in early life on body weight and corticosterone in adult offspring from ad libitum-fed and food-restricted rats.

The aims of this study were: (1) to assess the effects of maternal undernutrition during pregnancy on adult offspring with regard to growth, body composition and plasma levels of glucose, insulin and corticosterone, and (2) to investigate whether oxytocin treatment early in life could ameliorate the adverse effects of food restriction in utero. Pups from ad libitum-fed and food-restricted (60% of ad libitum intake during pregnancy) rats were injected subcutaneously once a day with oxytocin or saline on days 1-14 after birth. At adult age (62 days), male offspring from food-restricted dams had lower body weight, less adipose tissue, lower plasma glucose but higher corticosterone levels, compared to offspring from ad libitum-fed dams. However, oxytocin-treated food-restricted males had higher body weight, higher glucose and lower corticosterone levels compared to their saline-treated counterparts. In conclusion, oxytocin treatment early in life seems to ameliorate some of the adverse effects of food restriction in utero.

Aging↗

Engraftment and growth of transplanted pancreatic islets.

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.

Animals↗

Anatomical bases for paravertebral anesthetic block: fluid communication between the thoracic and lumbar paravertebral regions.

An injection of a local anesthetics in the paravertebral region produces an analgesic field on the same side of the body, a paravertebral block. One point in question about this block is whether the local anesthetic spreads from the thoracic to the lumbar level of the paravertebral region. The purpose of this study was to find how the anesthetic fluid traveled to the lumbar paravertebral region, if at all. Twelve cadavers were used in this study. 15 ml of crimson dye was injected into the paravertebral region at the 11th thoracic level. The viscerae were removed so that we could examine the dye spread. While the crimson dye spread in the endothoracic fascia posterior to the parietal pleura, it also spread downward in the fascia mostly along the splanchnic nerves. At the upper surface of the diaphragm the dye spread laterally in the fascia, and entered the abdominal cavity through the medial and lateral arcuate ligaments. In the abdominal cavity, the dye was found to have spread so widely in the transversalis fascia that the subcostal, iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous and femoral nerves were involved. We concluded that the dye in the thoracic paravertebral region can enter the abdominal cavity through the medial and lateral arcuate ligaments. This study explained possible fluid communication between the thoracic and lumbar paravertebral regions and confirmed our former clinical observations. The result is important for the future clinical application of paravertebral anesthesia.

Aged↗

The difference between delayed extubation and tracheostomy in post-operative sleep apnea after glossectomy or laryngectomy.

BACKGROUND: Patients with cancer of the tongue or larynx require glossectomies or laryngectomies and subsequent reconstruction. These procedures remove part of the patient's upper airway. In cancer of the tongue, the removed part of the airway is substituted by a flap of their skin. Post-operatively, it is possible that the patients have problems respiring comfortably. In addition to this, long surgical procedures may simply interfere with their circadian rhythm. To elucidate the possible change in their post-operative respiration, we monitored the patient's respiratory pattern with an apnea monitor. METHODS: We attached an apnea monitor to the patients and recorded their respiratory pattern and arterial oxygen saturation. The patients were monitored for a total of five days: three days prior to the operation, one day before the operation, the day of operation, two days after, and on the fourth day after the operation. The period of monitoring was from 8:00 p.m. to 6:00 a.m. the next morning. RESULTS: Sixteen patients completed this study. The patients whose tube was extubated after glossectomy showed frequent apnea, low mean oxygen saturation and low comfort score as compared to the patients with tracheostomy after laryngectomy. Because two failed cases of free skin flap were among the former, it is possible that the frequent apnea is a factor of failed free skin graft after glossectomy and laryngectomy. CONCLUSION: Further studies are required to improve the patient's respiration during their sleep after tracheal extubation in glossectomy.

Aged↗