Bengt Jeppsson - Academia.edu (original) (raw)

Papers by Bengt Jeppsson

Digestive Diseases and Sciences, Sep 29, 2006

Purpose: Ischaemia/reperfusion (I/R) of the colon is an inflammatory condition leading to tissue ... more Purpose: Ischaemia/reperfusion (I/R) of the colon is an inflammatory condition leading to tissue injury where reactive oxygen species play a central role. Rose hip is rich in biologically active polyphenols with antioxidative properties, which may be important in prevention of lipid peroxidation. L. plantarum DSM 9843 possesses enzymatic activity towards polyphenols. The objective of this study was to define the effect of oral administration of L. plantarum and rose hip in I/R injury. Results: Administration of rose hip and L. plantarum significantly decreased MDA levels in caecum tissue and Enterobacteriaceae counts in caecum stool. A positive correlation between MDA levels and Enterobacteriaceae counts was found. Conclusions: The results support a synergistic/additive role of rose hip and L. plantarum in reducing lipid peroxidation. Therefore rose hip and L. plantarum may be used as a pretreatment to tissue injuries, e.g. colonic surgery, organ transplantation and vascular surgery.

BMC Gastroenterology, 2022

Background Oral administration of health-promoting bacteria is increasingly used in clinical prac... more Background Oral administration of health-promoting bacteria is increasingly used in clinical practise. These bacteria have anti-inflammatory characteristics and modulate the immune system without major reported side effects. The mechanisms of action are not yet fully defined. Our aim was to study systemic effects of probiotics by measurements of leukocytes as well as local effects on rectal mucosal biopsies after adding a standardized inflammatory stimulus in vitro. Methods Fourteen healthy subjects were randomized to receive 1010 colony forming units/day orally of the probiotic strain Lactiplantibacillus plantarum 299 (Lp299), n = 7, or Bifidobacterium infantis CURE21 (CURE21), n = 7, for six weeks. Rectal biopsies were taken before and after ingestion of either probiotic strain product, for stimulation in vitro with tumour necrosis factor alpha (TNF-α) at 10 and 100 ng/ml respectively up to 8 h. Blood tests were sampled before and after treatment. Lactate dehydrogenase (LDH) confi...

International Journal of Food Sciences and Nutrition, 2021

The number of elderlies is increasing but prevalence of malnutrition has been reported. The aim o... more The number of elderlies is increasing but prevalence of malnutrition has been reported. The aim of the study was to determine the significance of short-term nutritional deficiencies in mice. Immune status was assessed through flow cytometry of leucocytes in Peyer's patches (PP) and mesenteric lymph nodes (MLN), and intestinal microbiota was evaluated by terminal restriction fragment length polymorphism (T-RFLP). C57BL/6NCrl mice fed standard diet (StD) or experimental diet high in fat, and low in carbohydrates, protein, fibre, vitamins, and minerals (ExpD) for 2 or 4 weeks. ExpDanimals gained less weight, increased liver lipids, and developed splenomegaly. Diet affected regulatory T-cells, gut homing receptors and TLR2 and TLR4 in PP and MLN and the microbiota was influenced. Partial least squares models on flow cytometry-and T-RFLP data demonstrated correlations between microbial communities and immune phenotyping. Our model shows similarities to malnourished elderly and interactions between intestinal bacteria and the immune system.

British Journal of Cancer, 1980

HPB Surgery, 1996

To evaluate the tolerance of the cirrhotic liver to extended warm ischaemia, 47 patients with cir... more To evaluate the tolerance of the cirrhotic liver to extended warm ischaemia, 47 patients with cirrhosis who underwent liver,resection over a 4-year period were studied retrospectively. Three groups of patients were identified. In group 1 (14 patients) liver resection was performed under conditions of portal triad occlusion ranging from 50 to 75 (mean 57.1) min. Group 2 (12 patients) was treated with portal occlusion for a period ranging from 30 to 42 (mean 33.1) min. Group 3 comprised 21 patients who underwent hepatectomy using conventional techniques. Mean blood loss was significantly reduced by portal triad occlusion (819 ml in group 1,523 ml in group 2) compared with the conventional techniques (1652 ml in group 3) (P<0.05, group 1 versus group 3; P<0.01, group 2 versus group 3). Hospital death occurred in three of the 21 patients in group 3 but in no patient who underwent portal triad occlusion. The morbidity rate was lower in the two occlusion groups (four of 26 patients)...

HPB Surgery, 1995

HPB INTERNATIONAL 203 surgery group. The procedure-related complications (28% and 32%, respective... more HPB INTERNATIONAL 203 surgery group. The procedure-related complications (28% and 32%, respectively) and 30 day mortality (8% and 20%) were similar. Although the initial hospital stay was significantly shorter in the stented group (18 vs 24 days), this difference was not maintained when readmissions for obstructed endoprostheses and duodenal obstruction were also considered. Another study by Dowsett et al. included 127 patients with unresectable malignancy obstructing the distalbile duct2. Sixty-five patients were treated via endoscopic stenting and 62 had surgical palliation. Successful biliary drainage was achieved in 94% of patients, with the 30 day mortality being 6% after

British Journal of Cancer, 1997

Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and c... more Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 nonadenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100% of the carcinomas, in 100% of the adenomas and in 37.5% of the non-adenomatous polyps, i.e. all ten lesions with a normal karyotype were histologically diagnosed as hyperplastic polyps. Although adenomas and carcinomas shared several karyotypic features, two chromosome aberrations, der(8;17)(q10;q10) and-14, were found in carcinomas but not in adenomas, indicating that they might be specifically associated with carcinoma development in the large bowel mucosa. The karyotypic similarity seen between the malignant and benign tumours in the same patient, and also sometimes among non-malignant polyps in the same case, indicates that these microscopically distinct lesions may be part of a single neoplastic clonal expansion.

Background. Systemic administration of antibiotics or selective decontamination is frequently use... more Background. Systemic administration of antibiotics or selective decontamination is frequently used in the prophylaxis and treatment of infections originating from the gastrointestinal flora. In this study, we wanted to compare the protective effect of enteral administration of lactobacilli to gentamicin against severe intra-abdominal infection. Methods. Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP). Rats were pretreated with saline, Lactobacillus R2LC, and gentamicin. Bacterial growth and endotoxin levels in the blood, reticuloendothelial system (RES)-function, and intestinal transit were determined up to 24 hours after CLP. Results. CLP-provoked bacteremia was significantly reduced by 48% and 55% in lactobacilli-and gentamicin-treated rats, respectively. Notably, CLP-induced endotoxemia was abolished at 12 hours, and reduced by 47% at 24 hours, in rats pretreated with lactobacilli. Gentamicin reduced endotoxin levels provoked by CLP by 86% at 12 hours, but had no effect at 24 hours. Lactobacilli had no effect on the clearance of Escherichia coli (E coli) from the blood, whereas intestinal transit was increased in lactobacilli-treated animals, suggesting that the beneficial effect of Lactobacillus R2LC is not related to an increase of phagocytic capacity but may rather be partly attributable to an enhanced intestinal motility. Conclusion. Enteral administration of Lactobacillus R2LC attenuates bacteremia and endotoxemia associated with intra-abdominal infection in rats. (Surgery 2003;134:467-73.

Nutrition, 1996

Acute liver failure is accompanied by a high rate of bacterial and septic complications. Arginine... more Acute liver failure is accompanied by a high rate of bacterial and septic complications. Arginine has a potent effect on the immune system and modulates bacterial clearance in septic models. We studied the effect of oral arginine supplementation on the extent of liver injury and the associated bacterial translocation in an acute liver injury model in rats. Sprague-Dawley rats were divided into normal, liver injury, and arginine-supplemented groups. In the arginine group, 2% arginine was supplemented daily through a nasogastric tube for 8 d. Acute liver injury was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body wt). Samples were collected 24 h after the liver injury. In the argininesupplemented group, alkaline phosphatase, bilirubin, and aspartate aminotransferase were reduced significantly compared with the acute liver injury control group. The results of bacterial translocation in the arginine-supplemented group showed a significantly reduced number of translocated bacteria to the liver and mesenteric lymph nodes than occurred in the acute liver injury group. The histological study of the liver in the arginine-supplemented group showed scattered areas of hepatocellular necrosis and inflammatory cell infiltration, and in the acute liver injury group there were more and widespread hepatocellular necrosis and inflammatory cell infiltration. Oral supplementation of arginine in an acute liver injury model improves significantly the state of the liver injury and reduces bacterial translocation to the liver and mesenteric lymph nodes. Nutrition 1996; 12:529-533

Journal of Innate Immunity, 2012

Streptococcal toxic shock syndrome is frequently caused by Streptococcus pyogenes of the M1 serot... more Streptococcal toxic shock syndrome is frequently caused by Streptococcus pyogenes of the M1 serotype. The aim of this study was to determine the role of Ras-homologous (Rho)-kinase signaling in M1 protein-provoked lung damage. Male C57BL/6 mice received the Rho-kinase-specific inhibitor Y-27632 before administration of M1 protein. Edema, neutrophil accumulation and CXC chemokines were quantified in the lung 4 h after M1 protein challenge. Flow cytometry was used to determine Mac-1 expression. Quantitative RT-PCR was used to determine gene expression of CXC chemokine mRNA in alveolar macrophages. M1 protein increased neutrophil accumulation, edema and CXC chemokine formation in the lung as well as enhanced Mac-1 expression on neutrophils. Inhibition of Rho-kinase signaling significantly reduced M1 protein-provoked neutrophil accumulation and edema formation in the lung. M1 protein-triggered pulmonary production of CXC chemokine and gene expression of CXC chemokines in alveolar macrop...

Inflammation Research, 2012

Objective P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in ... more Objective P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage. Methods Male C57BL/6 mice were treated with a control antibody or an anti-PSGL-1 antibody prior to cecal ligation and puncture (CLP). Leukocyte-endothelium interactions and microvascular hemodynamics were studied in pulmonary arterioles, capillaries and venules 4 h after CLP. Results Immunoneutralization of PSGL-1 decreased CLP-induced leukocyte rolling in pulmonary arterioles and venules significantly. Inhibition of PSGL-1 had no effect on leukocyte adhesion in venules, whereas the number of adherent leukocytes in lung arterioles and the number of trapped leukocytes in capillaries were markedly decreased. Moreover, immunoneutralization of PSGL-1 improved microvascular perfusion in the lung of septic animals. Conclusions Taken together, these results document that PSGL-1 mediates leukocyte rolling in arterioles and venules. However, inhibition of PSGL-1 only decreases leukocyte adhesion in arterioles, suggesting that leukocyte rolling is not a prerequisite for pulmonary venular adhesion of leukocytes in sepsis. In addition, our data show that capillary trapping of leukocytes is dependent on PSGL-1 function. Keywords Adhesion Á Inflammation Á Leukocyte Á Lung Á Rolling and selectins J. Roller and Y. Wang contributed equally.

Infection and Immunity, 2013

T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present... more T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present study, we hypothesized that Rho kinase signaling might regulate induction of T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were treated with the specific Rho kinase inhibitor Y-27632 (5 mg/kg of body weight) prior to cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation, and percentage of regulatory T cells (CD4 + CD25 + Foxp3 + ) were determined by flow cytometry. Formation of gamma interferon (IFN-γ) and interleukin 4 (IL-4) in the spleen and plasma levels of HMBG1, IL-17, and IL-6 were quantified by use of enzyme-linked immunosorbent assay (ELISA). It was found that CLP evoked apoptosis and decreased proliferation in splenic CD4 T cells. Inhibition of Rho kinase activity decreased apoptosis and enhanced proliferation of CD4 T cells in septic animals. In addition, CLP-evoked induction of regulatory T cells in the spleen was abolished by Rho kinase i...

Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2010

Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study... more Leukocytes mediate hepatocellular injury in obstructive cholestasis. The aim of the present study was to define the role of P-selectin glycoprotein ligand-1 (PSGL-1) in cholestasis-induced leukocyte recruitment and liver damage.

The British journal of nutrition, 2011

The aim of the present study was to assess the long-term effects of a high-energy-dense diet, sup... more The aim of the present study was to assess the long-term effects of a high-energy-dense diet, supplemented with Lactobacillus plantarum (Lp) or Escherichia coli (Ec), on weight gain, fattening and the gut microbiota in rats. Since the mother's dietary habits can influence offspring physiology, dietary regimens started with the dams at pregnancy and throughout lactation and continued with the offspring for 6 months. The weight gain of group Lp was lower than that of groups C (control) and Ec (P = 0·086). More retroperitoneal adipose tissue (P = 0·030) and higher plasma leptin (P = 0·035) were observed in group Ec compared with group Lp. The viable count of Enterobacteriaceae was higher in group Ec than in group Lp (P = 0·019), and when all animals were compared, Enterobacteriaceae correlated positively with body weight (r 0·428, P = 0·029). Bacterial diversity was lower in group Ec than in groups C (P ≤ 0·05) and Lp (P ≤ 0·05). Firmicutes, Bacteroidetes and Verrucomicrobia domin...

Gastroenterology, 2000

Leukocyte-endothelium interactions are dependent on a coordinated expression and function of spec... more Leukocyte-endothelium interactions are dependent on a coordinated expression and function of specific adhesion molecules. The objective of the present study was to examine the role of selectin function and leukocyte rolling in tumor necrosis factor-α (TNF-α)-induced leukocyte adhesion and extravasation in venules in vivo. For this purpose, we used intravital microscopy in the mouse cremaster muscle stimulated for 2-3 h with TNF-α intrascrotally. Pretreatment with fucoidan, which inhibits P-and L-selectin, and a P-selectin monoclonal antibody (RB40.34) abolished TNF-α-stimulated leukocyte rolling. This great reduction in rolling caused a marked attenuation of firm adhesion and extravascular accumulation of leukocytes. When fucoidan and RB40.34 were administrated after stimulation with TNF-α, it was found that leukocyte rolling was greatly reduced whereas the number of firmly adherent leukocytes was completely unchanged, suggesting that the inhibitory effect of blocking P-selectin function on firm leukocyte adhesion and recruitment was due to the reduction in leukocyte rolling along the endothelium. Moreover, pretreatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) and a platelet-activating factor (PAF)-receptor antagonist had no effect of TNF-α-induced leukocyte rolling and adhesion, indicating that molecules other than ICAM-1 and PAF mediate firm adhesion and recruitment of leukocytes in TNF-α-activated tissues. Taken together, our data demonstrate that P-selectin function plays an important role in TNF-α-induced inflammatory cell recruitment by mediating leukocyte rolling as a precondition for cytokine-provoked firm adhesion and transmigration in vivo. These findings, thus, suggest that inhibition of P-selectin may be a central target for pharmacological intervention in inflammatory diseases.

Carcinogenesis, 2005

It is well documented that prolonged inflammatory conditions, particularly those relating to the ... more It is well documented that prolonged inflammatory conditions, particularly those relating to the colon, have been shown to induce cancer. We have previously demonstrated that the pro-inflammatory mediator leukotriene D 4 (LTD 4) induces survival and proliferation in intestinal cells and that its receptor, CysLT 1 , is upregulated in human colon cancer tissue. Here we demonstrate, for the first time that in both Int 407 (a non-transformed human intestinal epithelial cell line) and Caco-2 cells (a human colorectal carcinoma cell line), cytosolic phospholipase A 2 a (cPLA 2 a) is activated and translocates to the nucleus upon LTD 4 stimulation via a calcium-dependent mechanism that involves activation of protein kinase C (PKC), and the mitogenactivated protein kinases ERK1/2 and p38. We also show with a cPLA 2 a promoter luciferase assay, that LTD 4 induces an increase in the transcriptional activity of cPLA 2 a via activation of cPLA 2 a and the transcription factor NFkB. Interestingly we demonstrate here that both the basal and the LTD 4-induced cPLA 2 a activity is elevated $3-fold in Caco-2 colon cancer cells compared with Int 407 cells. The difference in basal activity was confirmed in human colon tumor samples by the finding of a similar increase in cPLA 2 a activity when compared with normal colon tissue. A functional role of the increased cPLA 2 a activity in tumor cells was revealed by our findings that inhibition of this enzyme reduced both basal and LTD 4induced proliferation, the effects being most pronounced in Caco-2 tumor cells. The present data reveal that cPLA 2 a, an important intracellular signal activated by inflammatory mediators, is an important regulator of colon tumor growth.

British Journal of Pharmacology, 2009

Background and purpose: Neutrophil‐mediated lung injury is an insidious feature in sepsis althou... more Background and purpose: Neutrophil‐mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P‐selectin glycoprotein‐ligand‐1 (PSGL‐1) in sepsis‐induced neutrophil recruitment and tissue injury in the lung.Experimental approach: Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL‐1 and P‐selectin as well as a platelet‐depleting antibody directed against GP1bα.Key results: CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration and increased levels of CXC chemokines in the lung. Immunoneutralization of PSGL‐1 or P‐selectin reduced CLP‐induced neutrophil recruitment in the bronchoalveolar space by more than 56% and lun...

Pharmacology & Toxicology, 1987

Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) an... more Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes P-hexosaminidase (P-NAG) and P-glucuronidase (P-GLU) increased significantly after 24 hrs, while the level of P-GLU returned to normal after 48 hrs, but the activity of P-NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of P-NAG, but did not influence the histological changes.

Research in Experimental Medicine, 1987

In rats with a portacaval shunt (PCS), the effect on the serotonin metabolism in the brain after ... more In rats with a portacaval shunt (PCS), the effect on the serotonin metabolism in the brain after oral administration of blood, a mixed amino acid solution (Vamin 14; KabiVitrum, Sweden) or a 10% glucose solution was studied. One week after PCS, the animals were fed with a gastric tube for 8 h and thereafter tested for behavioral abnormalities before decapitation at 12 h. The concentration of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed chromatographically (HPLC technique with electrochemical detection) in different regions of the brain. Estimation of synthetic rates of 5-hydroxyindoles was facilitated by aromatic aminoacid decarboxylase inhibition (m-hydroxybenzylhydrazine; NSD 1015). The brain concentrations of 5-HTP, 5-HT, and 5-HIAA were increased in all shunted rats as compared with sham-operated animals. Whether animals received blood, glucose, or aminoacid solution made no differences in the brain concentrations of 5-HTP and 5-HT. Concentrations of 5-HIAA were lower in those animals receiving blood as compared with the other shunted groups. No reproducible differences in the behavior of the animals were observed. These results suggest that massive blood administration 1 week after PCS in rats has no influence on the rate of brain indole synthesis. While alterations in serotonin metabolism may play a role in some forms of encephalopathy, this study implies that the behavioral and neurologic disorders which follow gastrointestinal tract hemorrhage in patients with liver failure may have other etiologies.

World Journal of Surgery, 1987

The metabolism of monoamines in the brain of rats in fulminant hepatic failure was studied after ... more The metabolism of monoamines in the brain of rats in fulminant hepatic failure was studied after administration of branched chain amino acids (BCAA). Male Sprague-Dawley rats were exposed to a total hepatectomy or a sham operation and infused intravenously for 5 hours with a 10% glucose solution alone or 10% glucose + 0.24 mol/l BCAA (0.08 mol/l of each valine, leucine, and isoleucine). Thirty minutes before decapitation, a decarboxylase inhibitor (NSD 1015| blocking the conversion of 5-hydroxytryphtophan (5-HTP) to 5-hydroxytryptamine (5-HT), and dihydroxyphenylalanine (DOPA) to dopamine (DA), was injected intraperitoneally. The concentrations of 5-HTP, 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed by high-performance liquid chromatography, DOPA, DA, and norepinephrine (NE) by a radio-enzymatic method in 8 different regions of the brain and spinal cord. The concentrations of 5-HTP were increased in the brains of hepatectomized rats, indicating an increased synthesis rate of the indoleamines. After administration of BCAA to hepatectomized rats, the synthesis rate was decreased to normal or, in some brain regions, even to subnormal values. The brain and spinal cord concentrations of DOPA and DA were unchanged in hepatectomized rats compared to sham-operated animals, indicating an unchanged turnover of the catecholamines. The levels of NE in the diencephalon and in the spinal cord were decreased after hepatectomy. The level of consciousness was not influenced by the BCAA infusions. It is concluded that BCAA infusion may normalize brain indoleamine synthesis in hepatectomized rats, whereas the catecholamine synthesis and the level of consciousness are unaffected by the BCAA administration.