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Biomedical subjects

Stig Bengmark

Publications and source records attributed to Stig Bengmark.

33 records · Page 2Linked to original sources

Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats.

BACKGROUND: Bacterial translocation is one important cause of nosocomial infections following major abdominal surgery. Oral administration of probiotics has been proposed to diminish bacterial translocation. MATERIAL AND METHODS: In total 68 rats were divided into seven groups: five of the groups received standard rat chow and were subjected to either sham-operation, 70% liver resection, colonic anastomosis, or a combination of 30 or 70% liver resection with synchronous colonic anastomosis, respectively. In two additional groups with synchronous operation, a combination of four different lactic acid bacteria and four fibers was administered two times daily pre- and postoperatively. Bacterial concentrations in cecum, mesenteric lymph nodes, liver, and spleen were analyzed and blood cultures were taken 48 h after operation. Furthermore, the following parameters were assessed: histological changes in the intestine, intestinal paracellular permeability (Ussing chamber), bursting pressure of the colonic anastomosis, and mitosis rate of the remnant liver. RESULTS: Bacterial translocation was observed in all rats, except in the sham group. Following liver resection, the highest bacterial concentrations were seen in liver and spleen, following colon anastomosis in the mesenteric lymph nodes. Bacterial translocation was increased in the animals with combined operation, in parallel to the extent of liver resection. In rats with colon anastomosis, bacterial concentration in the cecum was also higher than in the sham group. Application of probiotics significantly decreased bacterial concentration in the lymph nodes. In addition, animals with a high cecal concentration of lactobacilli had less translocation than the others. No histological changes were observed in the intestine. Paracellular permeability for ions, but not for the larger molecule lactulose, was increased in the colon in all groups with colon anastomosis. The bursting pressure of the colon anastomosis was not significantly different between the groups. Seventy percent liver resection led to a high rate of hepatocyte mitosis, whereas combination with colon anastomosis impaired the regeneration process. CONCLUSION: Synchronous liver resection and colon anastomosis led to increased bacterial translocation compared to the single operations in the rat model. It is possible to diminish this process by oral administration of probiotics. Bacterial overgrowth in the cecum and impaired hepatic regeneration, but not histological changes or alterations of paracellular permeability, are potential pathogenic mechanisms for translocation in this setting.

Administration, Oral↗

NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium.

Little is known about the defensive mechanisms induced in epithelial cells by pathogenic versus probiotic bacteria. The aim of our study was to compare probiotic bacterial strains such as Escherichia coli Nissle 1917 with nonprobiotic, pathogenic and nonpathogenic bacteria with respect to innate defense mechanisms in the intestinal mucosal cell. Here we report that E. coli strain Nissle 1917 and a variety of other probiotic bacteria, including lactobacilli--in contrast to more than 40 different E. coli strains tested--strongly induce the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) in Caco-2 intestinal epithelial cells in a time- and dose-dependent manner. Induction of hBD-2 through E. coli Nissle 1917 was further confirmed by activation of the hBD-2 promoter and detection of the hBD-2 peptide in the culture supernatants of E. coli Nissle 1917-treated Caco-2 cells. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for induction of hBD-2 through E. coli Nissle 1917. Treatment with the NF-kappaB inhibitor Helenalin, as well as with SP600125, a selective inhibitor of c-Jun N-terminal kinase, blocked hBD-2 induction by E. coli Nissle 1917 in Caco-2 cells. SB 202190, a specific p38 mitogen-activated protein kinase inhibitor, and PD 98059, a selective inhibitor of extracellular signal-regulated kinase 1/2, were ineffective. This report demonstrates that probiotic bacteria may stimulate the intestinal innate defense through the upregulation of inducible antimicrobial peptides such as hBD-2. The induction of hBD-2 may contribute to an enhanced mucosal barrier to the luminal bacteria.

Binding Sites↗

Bio-ecological control of perioperative and ITU morbidity.

BACKGROUND: Perioperative and intensive therapy unit (ITU) morbidity and mortality has remained unchanged during the past several decades, and this at an unacceptably high level. It is most likely, in the EU countries annually, that more than 1 million people suffer severe sepsis and some 300,000 die. Pharmaceutical attempts at prevention and treatment have, despite extensive efforts, hitherto failed to improve outcome more significantly. Much supports the fact that sepsis and its severe consequences are results of a malfunctioning innate immune system, impaired by both lifestyle and disease. A series of mostly simple measures to prevent further deterioration of the immune system, and to boost it, is recommended. Among the measures recommended are some modifications of surgical and postoperative management: restricted use of antibiotics, attempts made to maintain salivation and GI secretions, omission of prophylactic gastric decompression, postoperative drainage and preoperative bowel preparation, restricted use of stored blood, avoidance of overload with nutrients, uninterrupted enteral nutrition but also tight blood glucose control, supply of antioxidants, administration of prebiotic fibre and probiotic lactic acid bacteria. Nutritional control of postoperative morbidity includes use of so-called synbiotics, e.g. a combination of bioactive lactic acid bacteria (LAB) and bioactive plant fibres. RESULTS: Dramatic reduction in (in reality, almost abolishment of) septic morbidity is reported following supplementation of specific bioactive lactic bacteria in combination with prebiotic plant fibres, as tried in controlled studies in connection with extensive abdominal operations, liver transplantation and severe acute pancreatitis.

Critical Care↗

Use of some pre-, pro- and synbiotics in critically ill patients.

Maintenance of the gut environment is a key factor in determining outcome in the care of critically ill and postoperative patients. It is especially important to maintain both gastrointestinal secretions, full of anti-infectious and anti-inflammatory compounds, and the gut flora. Prebiotics, usually polysaccharides, exhibit strong bio-activity and the ingestion of prebiotics has been shown to reduce the rate of infection and restore health in sick and postoperative patients. Probiotics may have at least five functions, all of great importance to the sick patients: the reduction or elimination of potentially pathogenic micro-organisms of various kinds; the reduction or elimination of various toxins, mutagens, carcinogens, etc.; modulation of the innate and adaptive immune defence mechanisms; the promotion of apoptosis; and the release of numerous nutrient, antioxidant, growth, coagulation and other factors necessary for recovery. A combination of pre- and probiotics is referred to as 'synbiotics'. Our experience of synbiotic treatment in critically ill patients is limited, but cutting-edge results from studies of severe acute pancreatitis, chronic hepatitis and liver transplantation offer great hope for the future. This is especially important as pharmaceutical treatment, including the use of antibiotics, has largely failed, and the medical world is in much need of new treatment paradigms.

Critical Illness↗

Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis.

Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor alpha (TNF-alpha) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll-like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF-alpha in response to endotoxin and Gram-positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF-alpha, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF-alpha production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF-alpha levels, and in vitro TNF-alpha production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram-positive bacteria. Endotoxin, TNF-alpha, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up-regulated in cirrhosis and correlated significantly with serum TNF-alpha and sTNFR levels. In vitro TNF-alpha production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up-regulation of PBMC expression of TLR2. Serum TNF-alpha levels were further increased and in vitro TNF-alpha production further reduced in most patients. In conclusion, up-regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram-positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF-alpha and sTNFR levels in cirrhosis.

Administration, Oral↗

Lactobacilli attenuate bacteremia and endotoxemia associated with severe intra-abdominal infection.

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.

Abdominal Abscess↗

Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients.

BACKGROUND: Early enteral nutrition with solutions containing prebiotics (fiber) and probiotics (Lactobacillus) is suggested to reduce bacterial translocation and minimize the incidence of infections after liver transplantation. METHODS: In a prospective, randomized placebo-controlled trial consisting of 95 patients, we compared the incidence of postoperative infections and other complications after liver transplantation among three different groups, all supplied with early enteral nutrition: (a) standard formula plus selective bowel decontamination (SBD), (b) fiber-containing formula plus living Lactobacillus plantarum 299, and (c) fiber-containing formula plus heat-killed L plantarum 299. RESULTS: The groups were comparable regarding preoperative American Society of Anesthesiologists classification, Child-Pugh classification of cirrhosis, operative data, and degree of immunosuppression. The patients who received living lactobacilli plus fiber developed significantly fewer bacterial infections (13%) than the patients with SBD (48%). The incidence of infections was 34% in the group with inactivated lactobacilli and fiber. Cholangitis and pneumonia were the leading infections and enterococci the most commonly isolated bacteria. In the living Lactobacillus group, the mean duration of antibiotic therapy, the mean total hospital stay, and the stay on the intensive care unit were also shorter than in the groups with inactivated lactobacilli and fiber as well as with SBD. However, these differences did not reach statistical significance. CONCLUSIONS: Early enteral nutrition with fiber-containing solutions and living L plantarum 299 was well tolerated. It decreases markedly the rate of postoperative infections both in comparison with inactivated L plantarum 299 and significantly with SBD and a standard enteral nutrition formula. As it is a cheap and feasible alternative to SBD, further studies should evaluate whether this ecoimmunonutrition should be already started while patients are on the waiting list for transplantation.

Anti-Bacterial Agents↗

Enteral nutrition in HPB surgery: past and future.

Perioperative nutrition has, during the past century, been transformed from a tool to provide calorie and nitrogen support to a tool to boost the immune system and increase resistance to complications. Despite all the progress in medicine and surgery, perioperative morbidity, the rate of infections, thrombosis, and the development of serosal adhesions has remained the same as long as can be judged, or at least during the past 80 years. Most prone to develop complications are persons above the age of 65 and persons with depressed immunity. About 80% of the immune system is localized in the gastrointestinal tract, which offers great opportunities for modulation through enteral nutrition. As the stomach has a tendency to develop postoperative paralysis, tube feeding is often necessary. In 1918, Andresen demonstrated the advantages of enteral nutrition, which already started on the operating table. Mulholland and colleagues and Rhoads and co-workers demonstrated, during the 1940s, certain advantages of enteral tube feeding. Also, the works by Alexander, Fischer, and Ryan, and their co-workers supported the value of early enteral feeding, and suggested enteral feeding as an effective tool to boost the immune system. It was, however, works published in the early 1990s, by Moore and colleagues and by Kudsk and colleagues, which made surgeons more aware of the advantages of early enteral nutrition. Surgery in the hepatobiliary pancreatic field is known to have a high rate of complications. Uninterrupted perioperative nutrition, i.e., nutrition during the night before, during surgery, and immediately after, offers a strong tool to prevent complications. It is essential that the nutrition also provides food for the colon, e.g., fiber and healthy bacteria (probiotics) to ferment the fiber and boost the immune system.

Acute Disease↗

Probiotics in health and disease in the pediatric patient.

Probiotics are truly a timeless concept. Initially standard components of the human diet, potentially beneficial bacteria and yeast have been eliminated systematically through modern methods of preparing and preserving foods. Although the concept of probiotics is not new, the science of probiotics is in its infancy. Only recently have techniques been developed to identify, culture, and produce the probiotics that are suitable for medical use consistently. Furthermore, the potential uses for these organisms may extend far beyond what originally was thought. In no way should probiotics be thought of as a panacea for the diseases described earlier; however, when used appropriately, they represent a potentially beneficial adjunct to other proved therapies and have the added benefit of providing a stabilizing influence on the delicate balance between the ecosystem that consists of the human and its flora.

Child↗

Gut microbial ecology in critical illness: is there a role for prebiotics, probiotics, and synbiotics?

Approximately 70% of the immune system is localized in the gastrointestinal tract: its glands, mucosa, and mucosa-associated lymphoid system. The system influences health conditions because it produces large amounts of important gastrointestinal secretions as rich as breast milk in health-supporting and disease-preventing factors, and because of its rich gastrointestinal flora. The intestine normally contains 10 times more microbes than there are eukaryotic cells in the entire body. The optimal function of these microbes depends on the supply of food destined for the colonic bacteria (fermentable fibers, complex proteins, gastrointestinal secretions). The consideration of these functions influences outcome. Unfortunately, the conditions (supply of drugs-especially antibiotics, and reduced supply of food-especially fruits and vegetables) in the modern ICU are extremely poor both for optimal gastrointestinal secretion and for flora and need more attention. To improve treatment, a supply of new and effective flora (probiotics) and food for the flora (prebiotics) is needed, from which numerous health-supporting products (synbiotics) will be produced and absorbed at the level of the mucosa, mainly in the lower gastrointestinal tract.

Critical Care↗

Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery.

OBJECTIVE: Early enteral nutrition with fiber-containing solutions plus Lactobacillus may reduce bacterial translocation and minimize the incidence of infections after surgery. METHODS: In a prospective, randomized trial in three groups (n = 30/group) of patients after major abdominal surgery, we compared our previous regimen with parenteral nutrition or fiber-free enteral nutrition (group A) with enteral fiber-containing nutrition with living Lactobacillus (group B) and heat-killed Lactobacillus (group C). The main endpoint was the development of bacterial infection. Other analyzed parameters were the durations of antibiotic therapy and hospital stay, non-infectious complications, side effects of the nutrition, and onset of bowel movement. Routine parameters, nutritional parameters, and cellular immune status in the blood were measured preoperatively and on 1, 5, and 10 d postoperatively. RESULTS: The incidence of infections was significantly lower (P = 0.01) in groups B and C with enteral nutrition containing fibers (10% each) than in group A (30%). Patients in group B received antibiotics for a significantly shorter time (P = 0.04) than did the patients in groups A and C. The length of hospital stay and the incidence of non-infectious complications did not differ significantly. Fibers and lactobacilli were well tolerated. There were no general benefits of living Lactobacillus as opposed to heat-killed Lactobacillus in the entire study population, but benefits were observed in the patients with gastric and pancreas resections, although no statistical analysis was done due to their small numbers. CONCLUSIONS: Early enteral nutrition with fiber-containing solutions reduced the rate of postoperative infections in comparison with parenteral nutrition and fiber-free enteral formula. Addition of living Lactobacillus seemed to increase the benefits in patients with gastric and pancreatic resections.

Aged↗

Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases.

BACKGROUND: The world suffers a tsunami of chronic diseases, and a typhoon of acute illnesses, many of which are associated with the inappropriate or exaggerated activation of genes involved in inflammation. Finding therapeutic agents which can modulate the inflammatory reaction is the highest priority in medical research today. Drugs developed by the pharmaceutical industry have thus far been associated with toxicity and side effects, which is why natural substances are of increasing interest. METHODS: A literature search (PubMed) showed almost 1500 papers dealing with curcumin, most from recent years. All available abstracts were read. Approximately 300 full papers were reviewed. RESULTS: Curcumin, a component of turmeric, has been shown to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFkappaB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases. CONCLUSIONS: Turmeric, an approved food additive, or its component curcumin, has shown surprisingly beneficial effects in experimental studies of acute and chronic diseases characterized by an exaggerated inflammatory reaction. There is ample evidence to support its clinical use, both as a prevention and a treatment. Several natural substances have greater antioxidant effects than conventional vitamins, including various polyphenols, flavonoids and curcumenoids. Natural substances are worth further exploration both experimentally and clinically.

Acute Disease↗

Modulation by enteral nutrition of the acute phase response and immune functions.

To use nutrition in order to limit the negative consequences of physical and mental stress is not new. Recent advances in immunology and particularly in the understanding of the chemical language used to communicate both by eukarytic and prokarotic cells has made it easier to objectively evaluate effects of various immunomodulating efforts including the use of nutrients, vitamins and antioxidants in preventing or limiting the development of disease and its late consequences.

Acute-Phase Reaction↗