| 1. |
- Li Zweifel, Ulla, et al.
(author)
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God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 2: God miljöstatus och miljökvalitetsnormer
- 2012
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Reports (other academic/artistic)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att bestämma vad som kännetecknar god miljöstatus i respektive förvaltningsområde samt att ta fram miljökvalitetsnormer. God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för 11 temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. I Sverige har god miljöstatus formulerats för samtliga 29 kriterier som ska beaktas enligt direktivet. Dessa kvalitativa beskrivningar anger vad som kännetecknar god miljöstatus i Nordsjön och Östersjön. För att praktiskt bedöma om god miljöstatus har uppnåtts föreslås 37 nationella indikatorer. En uppsättning av indikatorer omfattar miljöns tillstånd och avspeglar ekosystemets komponenter i form av nyckelarter, samhällen, och livsmiljöer. En utgångspunkt vid val av indikatorer för miljöns tillstånd har varit koppling till de belastningar som i den inledande bedömningen av miljötillståndet i Nordsjön och Östersjön bedömts ha stor negativ påverkan på ekosystemet. En annan uppsättning indikatorer berör påverkan och belastning på miljön i form av tillförsel av näringsämnen och farliga ämnen, samt biologisk och fysisk störning av miljön. Tillsammans utgör indikatorerna ett verktyg för att följa utvecklingen av miljötillståndet och effekter av åtgärder i havsmiljön. Vid val av indikatorer har arbetet delvis utgått från existerande miljöövervakning och redan utvecklade indikatorer. Med denna utgångspunkt uppfylls en rad av havsmiljödirektivets krav, bland annat en god uppföljning av effekter av tillförsel av näringsämnen. Funktionella indikatorer, det vill säga indikatorer som utvärderats och för vilka god miljöstatus har definierats, saknas dock för tio av havsmiljödirektivets 29 kriterier. För uppföljning av biologisk mångfald saknas bland annat miljöövervakning och metoder för att bedöma livsmiljöers tillstånd. För att kunna bedöma fysiska skador på havsbotten saknas en övergripande sammanställning av information om aktiviteter som påverkar havsbottnar samt metodik för att bedöma effekterna. Det saknas också utvecklade indikatorer för det kriterium som berör uppföljning av storleks- och åldersstruktur hos fiskar. Brist på kunskap gör också att inga förslag på svenska indikatorer kan ges för effekter på levande organismer från marint avfall, undervattensbuller, och främmande arter samt att endast ett begränsat antal indikatorer tagits fram som speglar effekter av farliga ämnen. De indikatorer som fastställs i juli 2012 utgör således inte en slutlig lista för att följa upp havsmiljödirektivet. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där nästa steg är att anpassa miljöövervakningsprogrammen till uppföljning av miljötillståndet med valda indikatorer senast år 2014 samt att ta fram åtgärdsprogram till år 2015. God miljöstatus ska uppnås genom tillämpning av miljökvalitetsnormer det vill säga rättsligt bindande regler som avspeglar den lägsta godtagbara miljökvaliteten i Nordsjön och Östersjön. För att nå god miljöstatus har elva svenska miljökvalitetsnormer formulerats. Dessa miljökvalitetsnormer omfattar belastning i form av näringsämnen, farliga ämnen, främmande arter, uttag av arter, fysisk påverkan på havsbottnar och avfall i havsmiljön. Målsättningen har varit att utforma miljökvalitetsnormer som motsvarar alla de belastningar som i den inledande bedömningen har identifierats ha en stor påverkan på miljön.
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| 2. |
- Appelqvist, Hanna, et al.
(author)
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Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183
- 2012
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In: Annals of Clinical and Laboratory Science. - : Institute for Clinical Science. - 0091-7370 .- 1550-8080. ; 42:3, s. 231-242
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Journal article (peer-reviewed)abstract
- Bax-mediated permeabilization of the outer mitochondrial membrane and release of apoptogenic factors into the cytosol are key events that occur during apoptosis. Likewise, apoptosis is associated with permeabilization of the lysosomal membrane and release of lysosomal cathepsins into the cytosol. This report identifies proteolytically active cathepsin D as an important component of apoptotic signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome-mediated cell death is associated with degradation of Bax sequestering 14-3-3 proteins, cleavage of the Box activator Bid, and translocation of Box to mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be reproduced by enforced lysosomal membrane permeabilization, using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from purified mitochondria, indicating that the fragments generated are functionally active. Moreover, apoptosis was associated with cytosolic acidification, thereby providing a more favorable environment for the cathepsin D-mediated cleavage of Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated cytochrome c release by proteolytic activation of Bid.
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| 3. |
- Evilevitch, L., et al.
(author)
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Three-Day Enteral Exposure to a Red Kidney Bean Lectin Preparation Enhances the Pancreatic Response to CCK Stimulation in Suckling Pigs.
- 2005
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In: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 87:1, s. 20-25
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Journal article (peer-reviewed)abstract
- Background: A reason for the digestive problems that often occur around early weaning in piglets could be that the pancreas is not yet fully developed and the enzymes required for degradation of the solid food are not secreted in enough amounts. Objectives: The aim of the study was to investigate the possibility of inducing pancreas maturation with enhanced enzyme secretion. Methods: 10-day-old suckling pigs were gavage fed with a red kidney bean lectin preparation for 3 days, and the pancreatic response to intravenous infusion of CCK-33 was measured in the anaesthetized animals fitted with pancreatic duct catheters. Results: The pancreatic fluid secretion, protein output, and the trypsin and amylase outputs were significantly increased in response to CCK stimulation after the lectin treatment, as compared to those of the control littermates (p le 0.05). In addition, the plasma insulin basal levels and those observed during CCK-33 stimulation were lower in the lectin-treated piglets. Conclusion: The results suggested that the lectin treatment led to an increase in the capacity for pancreatic enzyme secretion in the suckling piglets. An enhanced pancreatic function might help to ameliorate the problems that may appear in modern pig production which are associated with weaning.
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| 4. |
- Fåk, Frida, et al.
(author)
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Age-related Effects of the Probiotic Bacterium Lactobacillus plantarum 299v on Gastrointestinal Function in Suckling Rats
- 2008
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In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 53:664-671, s. 664-671
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Journal article (peer-reviewed)abstract
- The effect of a probiotic bacterium on gut function was studied in neonatal animals by using a model with suckling rats. Lactobacillus plantarum 299v (Lp299v) or saline (controls) was fed (3.0 x 10(6) CFU/g b.wt per day) for one week to rats aged either 3, 7 or 14 days, after which bacterial colonization, gut growth, and functional parameters were analyzed. In rats fed with Lp299v from 3 to 10 days of age, an increase in ceacal lactobacilli was correlated with reduced intestinal macromolecular permeability and increased mucosal protein compared to age-matched controls. Pups treated from 7 to 14 days of age showed a decrease in pancreas weight and protein content, whereas pups treated from 14 to 21 days of age showed little effect of the Lp299v treatment. The results indicated that the bacterial exposure affected the gut function, where the effects were age-related and the youngest rats appeared most sensitive.
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| 5. |
- Kruszewska, Danuta, et al.
(author)
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Enteral crude red kidney bean (Phaseolus vulgaris) lectin--phytohemagglutinin--induces maturational changes in the enterocyte membrane proteins of suckling rats.
- 2003
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In: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 84:2, s. 152-158
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Journal article (peer-reviewed)abstract
- This study aimed to investigate the effect of enterally administered crude red kidney bean (Phaseolus vulgaris) lectin, PHA, on the expression of brush-border membrane vesicle (BBMV) proteins, in particular Na+/H+ exchangers (NHEs), in the small intestine of suckling rats. Gavage of PHA to 14-day-old rats for 3 days resulted in altered protein/glycoprotein patterns as analyzed by SDS-PAGE. Immunoblots demonstrated the appearance of two 71- and 27-kD protein bands indicative for NHE3 - one of the NHE isoforms - and PHA, respectively. PHA treatment also resulted in an augmented uptake of 22Na+ by the BBMV indicating an increase in NHE activity. Overall, the data suggests that enteral PHA exposure may induce maturational changes in enterocyte membrane proteins in young rats. In view of these findings, an investigation into the addition of PHA to infant formulas and weaning diets is warranted.
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| 6. |
- Lagerlöf, Ingemar, et al.
(author)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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In: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Journal article (peer-reviewed)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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| 7. |
- Linderoth, Ann, et al.
(author)
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Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the gastrointestinal tract of suckling rats
- 2006
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In: British Journal of Nutrition. - 1475-2662. ; 95:1, s. 105-115
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Journal article (peer-reviewed)abstract
- Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14 d old, were fed a single dose of PHA (0.05 mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3 d after treatment. Initially, at 1-24 h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3 d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut.
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| 8. |
- Linderoth, Ann, et al.
(author)
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Enterally but not parenterally administered Phaseolus vulgaris lectin induces growth and precocious maturation of the gut in suckling rats
- 2006
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In: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 89:1-3, s. 60-68
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Journal article (peer-reviewed)abstract
- Background: The lectin, phytohemagglutinin (PHA) has been shown to induce growth and functional maturation of the gastrointestinal (GI) tract in suckling rats. Objectives: To investigate the effect of the administration route, and whether enteral exposure to PHA was necessary to induce functional maturation. Methods: Fourteen-day-old rats were daily administered PHA via orogastric feeding (0.05 mg PHA/g BW) or via subcutaneous injection (0.05 or 0.005 mg PHA/g BW) for 3 days, while the controls received saline orogastrically. At 17 days of age, organ weight, intestinal and pancreatic function, and plasma corticosterone levels were analyzed. Moreover, 14-days old pups receiving a single dose of PHA, enterally or parenterally, were sacrificed after 12 h and examined for organ PHA binding using immunohistochemistry. Results: Enteral PHA exposure resulted in PHA binding in the epithelial lining of the small intestine, increased gastrointestinal growth, reduced intestinal macromolecular absorption, altered the disaccharidase expression towards an adult-like pattern, and increased the pancreatic protein and trypsin contents. In contrast, parenteral PHA exposure (high dose) resulted in PHA-binding in extra-intestinal organs, increased liver and spleen weight, and decreased thymus weight. Moreover, the intestinal maltase activity increased moderately, and the transfer of BSA to blood plasma was partially reduced. Both PHA treatments led to elevated plasma corticosterone levels. Conclusion: These results demonstrated that enteral exposure to PHA was necessary to induce the precocious maturation of the GI tract and the pancreas, while parenteral administration affects the extra-intestinal organs. Furthermore, the enteral effects were probably not mediated via a corticosteroid dependent pathway.
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| 9. |
- Linderoth, Ann, et al.
(author)
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Induced Growth and Maturation of the Gastrointestinal Tract After Phaseolus vulgaris Lectin Exposure in Suckling Rats
- 2005
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In: Journal of Pediatric Gastroenterology and Nutrition - Jpgn. - 1536-4801. ; 41:August, s. 195-203
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Journal article (peer-reviewed)abstract
- Objectives: In mammals, the postnatal development of the gastrointestinal tract is characterized by vast structural and functional changes. Using a suckling rat model, we investigated whether red kidney bean lectin, phytohemagglutinin (PHA), a potent gut mitogen in adult rats, can accelerate the growth and maturation of the gastrointestinal tract. Methods: At either 10 or 14 days of age, suckling rats were daily gavage fed with PHA (0.05 mg/g body weight) or saline for 3 days. At 1 or 3 days after this treatment, gastrointestinal organ growth, intestinal morphology, disaccharidase pattern, macromolecular absorption capacity, and pancreatic enzyme contents were studied. Results: After PHA exposure, increased small intestinal growth and number of crypt cells were observed, whereas the proportion of enterocytes with supranuclear vacuoles in the distal intestine was decreased. The macromolecular absorption of the markers bovine immunoglobulin (Ig)G and bovine serum albumin and plasma levels of maternal IgG decreased, and intestinal disaccharidases switched toward an adult-like pattern. The pancreas weight and pancreatic protein and trypsin contents increased. These changes were partly reversible when the PHA treatment began at 10 days of age, but they persisted when the treatment began at 14 days of age. Conclusions: PHA induced enhanced growth and precocious functional maturation of the gastrointestinal tract in suckling rats. The effects persisted if the PHA treatment started at 14 days of age, but not before, suggesting an age dependent mechanism. These findings may lead to a better understanding of gastrointestinal maturation and constitute a basis for the treatment of mammals having an immature gut.
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| 10. |
- Linderoth, Ann
(author)
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Induced Growth and Precocious Maturation of the Digestive System in Suckling Rats and Pigs after Exposure to Red Kidney Bean Lectin
- 2006
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Doctoral thesis (other academic/artistic)abstract
- The timing of the postnatal development of the gastrointestinal (GI) tract in mammals is influenced by dietary and hormonal factors. It was hypothesized that accelerated GI cell turnover during maturation would result in a precoucios conversion to more mature digestive functions. Thus, it was investigated if red kidney bean lectin, phytohaemagglutinin (PHA) - a potent gut mitogen in adult rats - could accelerate the growth and maturation of the digestive system in suckling rats and piglets. Suckling rats and piglets were dosed with PHA either via enteral or parenteral administration for up to three consecutive days prior to natural weaning. The binding of PHA to the GI tract and extra-intestinal organs, GI organ growth, intestinal morphology and proliferation, disaccharidase activity pattern, and macromolecular absorption capacity were studied, as well as the pancreatic enzyme contents. Changes in these parameters were considered to be markers for maturation or development towards an adult-like GI function. Furthermore, the plasma levels of corticosterone and insulin (rat), and cholecystokinin (pig), were investigated. It was concluded that preweaning enteral exposure to PHA in suckling rats accelerated growth and induced precocious functional maturation of the GI tract and the pancreas. Similar results were also achieved when a crude PHA preparation was fed to suckling piglets. PHA treatment induced irreversible changes of the gut resembling those occurring at natural weaning, such as a reduced macromolecular absorption (intestinal closure), altered disaccharidase expression towards an adult-like activity pattern, and enhanced pancreas function. The ability of PHA to induce GI functional maturation in rats was age-dependent. Also, a direct binding and interaction of PHA with the GI epithelium was found to be a prerequisite to induce functional maturation, since parenteral administration had little effect. Shortly after administration, the binding of PHA to the intestinal epithelium temporarily caused mucosal disarrangement and functional impediment of the GI tract, probably resulting in the release of hormones and inflammatory cytokines. During a later phase, this led to a stimulatory response of the GI tract, as seen by an increase in crypt cell proliferation, gut growth, and the emergence of more adult-like enterocytes. Taking into consideration the temporal differences between rats and piglets with respect to natural maturational events, it was suggested that PHA exerted gut maturing effects in piglets and probably also in other mammals. Thus, these findings might lead to a better understanding of the role of the diet in GI functional maturation.
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