Obesity, the deadly quartet and the contribution of the neglected daily organ rest - a new dimension of un-health and its prevention.

The "deadly quartet": excessive weight, hypertension, impaired glucose homeostasis, and atherogenic dyslipidemia constitute a greater threat to health than the added effects of smoking and alcohol abuse. It is strongly associated with unrestricted consumption of processed, refined foods. Recent observations from experience in South East Asia shows that the interval between lifestyle changes and associated change in disease pattern is shorter than earlier believed. Recent experience from obesity studies in Africa demonstrates not only dramatic changes in health but also large social consequences from being overweight. Obesity is not only a result of overeating - dozens of other factors are known to contribute. Our palaeolithic forefathers and those living a similar lifestyle today are reported to rarely have diseases and to live a long life. One such group is the Hunzas, living in Northern Pakistan, are reported to live on a daily 1,800-calorie 99% plant-based diet, consisting in 73% of mostly unrefined/unprocessed carbohydrates, 17% fat and 10% protein. They, and most likely also our forefathers, do/did most likely only eat twice a day, at noon and early evening. Calorie-restriction (CR) and also fasting was early recommended and has been so during thousands of years - early Greek medicine and giants such as Hippocrates, Galenus and later also Paracelsus prescribed restrictions in eating and fasting. So did Middle Age physicians and other nutrition experts such as Louis Cornado. Today it is again practiced around the World. Overeating and heavy postprandial metabolism is a great burden to the body causing elevated levels in blood of endotoxin, increased inflammatory and oxidative stress, release of tumor necrosis factor-α, and other pro-inflammatory cytokines, increases in numbers of and activating of leukocytes, a reaction that is potentiated by the presence of large-chain fatty acids and sugars. Various metabolic, uremic, microbiota-derived and environmental poisons accumulate in large amounts in the adipose tissues. High levels of poisons in the adipose tissues decreases the turnover of fats in order to protect other organs. The content in adipose of POPs - altogether 17 dioxins/furans and 18 polychlorinated biphenyl congeners, has been reported to be 2-3 times higher in obese compared to lean persons. Daily fasting consisting in 16 to 18 hours of avoidance of calorie intake offers an interesting alternative. An attractive policy is to abstain from eating between 18:00 in the evening and 10:00 or 12:00 AM, a plan, which I personally have practiced during many years.

Nutrition of the critically ill — a 21st-century perspective.

Health care-induced diseases constitute a fast-increasing problem. Just one type of these health care-associated infections (HCAI) constitutes the fourth leading cause of death in Western countries. About 25 million individuals worldwide are estimated each year to undergo major surgery, of which approximately 3 million will never return home from the hospital. Furthermore, the quality of life is reported to be significantly impaired for the rest of the lives of those who, during their hospital stay, suffered life-threatening infections/sepsis. Severe infections are strongly associated with a high degree of systemic inflammation in the body, and intimately associated with significantly reduced and malfunctioning GI microbiota, a condition called dysbiosis. Deranged composition and function of the gastrointestinal microbiota, occurring from the mouth to the anus, has been found to cause impaired ability to maintain intact mucosal membrane functions and prevent leakage of toxins - bacterial endotoxins, as well as whole bacteria or debris of bacteria, the DNA of which are commonly found in most cells of the body, often in adipocytes of obese individuals or in arteriosclerotic plaques. Foods rich in proteotoxins such as gluten, casein and zein, and proteins, have been observed to have endotoxin-like effects that can contribute to dysbiosis. About 75% of the food in the Western diet is of limited or no benefit to the microbiota in the lower gut. Most of it, comprised specifically of refined carbohydrates, is already absorbed in the upper part of the GI tract, and what eventually reaches the large intestine is of limited value, as it contains only small amounts of the minerals, vitamins and other nutrients necessary for maintenance of the microbiota. The consequence is that the microbiota of modern humans is greatly reduced, both in terms of numbers and diversity when compared to the diets of our paleolithic forebears and the individuals living a rural lifestyle today. It is the artificial treatment provided in modern medical care - unfortunately often the only alternative provided - which constitute the main contributors to a poor outcome. These treatments include artificial ventilation, artificial nutrition, hygienic measures, use of skin-penetrating devices, tubes and catheters, frequent use of pharmaceuticals; they are all known to severely impair the microbiomes in various locations of the body, which, to a large extent, are ultimately responsible for a poor outcome. Attempts to reconstitute a normal microbiome by supply of probiotics have often failed as they are almost always undertaken as a complement to - and not as an alternative to - existing treatment schemes, especially those based on antibiotics, but also other pharmaceuticals.

Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection.

BACKGROUND: Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. METHODS: This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10(10) each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. RESULTS: Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. CONCLUSIONS: Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. TRIAL REGISTRATION: Clinical Trials.gov: NCT00688311.

Pro- and synbiotics to prevent sepsis in major surgery and severe emergencies.

Septic morbidity associated with advanced surgical and medical treatments is unacceptably high, and so is the incidence of complications occurring in connection with acute emergencies such as severe trauma and severe acute pancreatitis. Only considering the US, it will annually affect approximately (app) 300 million (mill) of a population of almost one million inhabitants and cause the death of more than 200,000 patients, making sepsis the tenth most common cause of death in the US. Two major factors affect this, the lifestyle-associated increased weakness of the immune defense systems, but more than this the artificial environment associated with modern treatments such as mechanical ventilation, use of tubes, drains, intravascular lines, artificial nutrition and extensive use of synthetic chemical drugs, methods all known to reduce or eliminate the human microbiota and impair immune functions and increase systemic inflammation. Attempts to recondition the gut by the supply of microorganisms have sometimes shown remarkably good results, but too often failed. Many factors contribute to the lack of success: unsuitable choice of probiotic species, too low dose, but most importantly, this bio-ecological treatment has never been given the opportunity to be tried as an alternative treatment. Instead it has most often been applied as complementary to all the other treatments mentioned above, including antibiotic treatment. The supplemented lactic acid bacteria have most often been killed already before they have reached their targeted organs.

Nutrition of the critically ill - emphasis on liver and pancreas.

About 25 million individuals undergo high risk surgery each year. Of these about 3 million will never return home from hospital, and the quality of life for many of those who return is often significantly impaired. Furthermore, many of those who manage to leave hospital have undergone severe life-threatening complications, mostly infections/sepsis. The development is strongly associated with the level of systemic inflammation in the body, which again is entirely a result of malfunctioning GI microbiota, a condition called dysbiosis, with deranged composition and function of the gastrointestinal microbiota from the mouth to the anus and impaired ability to maintain intact mucosal membrane functions and prevent leakage of toxins-bacterial endotoxins and whole or debris of bacteria, but also foods containing proteotoxins gluten, casein and zein and heat-induced molecules such as advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). Markedly lower total anaerobic bacterial counts, particularly of the beneficial Bifidobacterium and Lactobacillus and higher counts of total facultative anaerobes such as Staphylococcus and Pseudomonas are often observed when analyzing the colonic microbiota. In addition Gram-negative facultative anaerobes are commonly identified microbial organisms in mesenteric lymph nodes and at serosal "scrapings" at laparotomy in patients suffering what is called "Systemic inflammation response system" (SIRS). Clearly the outcome is influenced by preexisting conditions in those undergoing surgery, but not to the extent as one could expect. Several studies have for example been unable to find significant influence of pre-existing obesity. The outcome seems much more to be related to the life-style of the individual and her/his "maintenance" of the microbiota e.g., size and diversity of microbiota, normal microbiota, eubiosis, being highly preventive. About 75% of the food Westerners consume does not benefit microbiota in the lower gut. Most of it, refined carbohydrates, is already absorbed in the upper part of the GI tract, and of what reaches the large intestine is of limited value containing less minerals, less vitamins and other nutrients important for maintenance of the microbiota. The consequence is that the microbiota of modern man has a much reduced size and diversity in comparison to what our Palelithic forefathers had, and individuals living a rural life have today. It is the artificial treatment provided by modern care, unfortunately often the only alternative, which belongs to the main contributor to poor outcome, among them; artificial ventilation, artificial nutrition, hygienic measures, use of skin penetrating devices, tubes and catheters, frequent use of pharmaceuticals, all known to significantly impair the total microbiome of the body and dramatically contribute to poor outcome. Attempts to reconstitute a normal microbiome have often failed as they have always been undertaken as a complement to and not an alternative to existing treatment schemes, especially treatments with antibiotics. Modern nutrition formulas are clearly too artificial as they are based on mixture of a variety of chemicals, which alone or together induce inflammation. Alternative formulas, based on regular food ingredients, especially rich in raw fresh greens, vegetables and fruits and with them healthy bacteria are suggested to be developed and tried.

Nutrigenomics therapy of hepatisis C virus induced-hepatosteatosis.

Nutrigenomics is a relatively new branch of nutrition science, which aim is to study the impact of the foods we eat on the function of our genes. Hepatosteatosis is strongly associated with hepatitis C virus infection, which is known to increase the risk of the disease progression and reduce the likelihood of responding to anti- virus treatment. It is well documented that hepatitis C virus can directly alter host cell lipid metabolism through nuclear transcription factors. To date, only a limited number of studies have been on the effect of human foods on the nuclear transcription factors of hepatitis C virus -induced hepatosteatosis.Three nutrients, selected among 46 different nutrients: beta-carotene, vitamin D2, and linoleic acid were found in a cell culture system to inhibit hepatitis C virus RNA replication. In addition, polyunsaturated fatty acids (PUFAs) especially arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) have been demonstrated to inhibit hepatitis C virus RNA replication. These PUFAs, in particular the highly unsaturated n-3 fatty acids change the gene expression of PPARa and SREBP, suppress the expression of mRNAs encoding key metabolic enzymes and hereby suppress hepatic lipogenesis and triglyceride synthesis, as well as secretion and accumulation in tissues. A recent prospective clinical trial of 1,084 chronic hepatitis C patients compared to 2,326 healthy subjects suggests that chronic hepatitis C patients may benefit from strict dietary instructions.Increasing evidence suggest that some crucial nuclear transcription factors related to hepatitis C virus -associated hepatosteatosis and hepatitis C virus RNA itself can be controlled by specific anti- hepatitis C virus nutrition. It seems important that these findings are taken into account and specific nutritional supplements developed to be used in combination with interferon as adjunctive therapy with the aim to improve both the early as well as the sustained virological response.

The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD).

Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease.

Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats.

BACKGROUND: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections. MATERIAL AND METHODS: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state. RESULTS: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group. CONCLUSION: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Inhibitory effect of curcumin on early liver regeneration following partial hepatectomy in rats.

BACKGROUND: Curcumin (Cur) is a nontoxic, hepatoprotective antioxidant. Recent investigations have demonstrated a protective effect of curcumin pretreatment during cold ischemia of hepatocytes, but its impact on liver regeneration per se has not been investigated so far. MATERIAL AND METHODS: Male Sprague-Dawley rats (n = 6 per group) underwent sham operation, 70% partial hepatectomy (PH), or PH with curcumin application (100 mg per kg bodyweight per day) starting 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver regeneration was analyzed by measurement of relative liver weight, mitotic-index, bromo-deoxy-uridine (BrdU)-incorporation and Ki-67 expression. RESULTS: The relative liver weight 24 h after surgery was similar in the PH groups with and without curcumin treatment. Also, a comparably high number of Ki-67 positive proliferating hepatocytes was detected in both groups. In contrast, the mitotic index in the untreated PH group (83 +/- 20 mitosis/2000 hepatocytes) was significantly higher than in the curcumin treated group (21 +/- 6). The BrdU labeling index was slightly higher in the curcumin treated group with PH (24% +/- 5%) than in the untreated group (16% +/- 2%). The hepatocyte density as marker of cellular hypertrophy was significantly lower in the curcumin group (474 +/- 23) than in the untreated group (609 +/- 22). CONCLUSIONS: Curcumin inhibits cell cycle progression during normal liver regeneration in rats, predominantly at the level of the G2/M transition point. However, the total liver mass and function was not significantly altered. Nevertheless, application of curcumin in conditions of high physiological cell proliferation should be performed with caution.

Advanced glycation and lipoxidation end products--amplifiers of inflammation: the role of food.

BACKGROUND: High levels of glycated and lipoxidated proteins and peptides in the body are repeatedly associated with chronic diseases. These molecules are strongly associated with activation of a specific receptor called RAGE and a long-lasting exaggerated level of inflammation in the body. METHODS: PubMed reports over 5000 papers plus >13,500 articles about the related HbA(1c), most of them published in the past 5 years. Most of the available abstracts have been read and approximately 800 full papers have been studied. RESULTS: RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation end products, known since 1992, functions as a master switch, induces sustained activation of nuclear factor kappaB (NFkappaB), suppresses a series of endogenous autoregulatory functions, and converts long-lasting proinflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and is strongly associated with a series of diseases from allergy and Alzheimers to rheumatoid arthritis and urogenital disorders. Heat treatment, irradiation, and ionization of foods increase the content of dysfunctioning molecules. CONCLUSIONS: More than half of the studies are performed in diabetes and chronic renal diseases; there are few studies in other diseases. Most of our knowledge is based on animal studies and in vitro studies. These effects are worth further exploration both experimentally and clinically. An avoidance of foods rich in deranged proteins and peptides, and the consumption of antioxidants, especially polyphenols, seem to counteract such a development.

Probiotics potentiate IL-6 production in IL-1beta-treated Caco-2 cells through a heat shock-dependent mechanism.

IL-6 may exert anti-inflammatory and protective effects in intestinal mucosa and enterocytes. The influence of probiotics on mucosal and enterocyte IL-6 production is not known. We tested the hypothesis that the probiotic bacteria Lactobacillus paracasei and Lactobacillus plantarum regulate IL-6 production in intestinal epithelial cells. Cultured Caco-2 cells were treated with 1 ng/ml of IL-1beta in the absence or presence of different concentrations of L. paracasei or L. plantarum followed by measurement of IL-6 production. The role of heat shock response was examined by determining the expression of heat shock protein 70 (hsp70) and hsp27, by downregulating their expression with small interfering RNA (siRNA), or by treating cells with quercetin. Treatment of the Caco-2 cells with IL-1beta resulted in increased IL-6 production, confirming previous reports from this laboratory. Probiotics alone did not influence IL-6 production, but the addition of probitoics to IL-1beta-treated cells resulted in a substantial augmentation of IL-6 production. Treatment of the Caco-2 cells with live L. paracasei increased cellular levels of hsp70 and hsp27 and the potentiating effect on IL-6 production was inhibited by quercetin and by hsp70 or hsp27 siRNA. Results suggest that probiotics may enhance IL-6 production in enterocytes subjected to an inflammatory stimulus and that this effect may, at least in part, be heat shock dependent.

Effect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial.

OBJECTIVE: Patients undergoing pancreas resection carry several risk factors for nosocomial bacterial infections. Pre- and probiotics (synbiotics) are potentially useful for prevention of these infections. SUMMARY BACKGROUND DATA: First trials in patients following major abdominal surgery including liver transplantation using one Lactobacillus (LAB) and one fiber showed significant reduction of infection rates and reduced length of antibiotic therapy compared with a control group. The present study was designed to analyze whether a combination of different LAB and fibers would further improve outcome. METHODS: A prospective randomized monocentric double-blind trial was undertaken in 80 patients following pylorus-preserving pancreatoduodenectomy (PPPD). All patients received enteral nutrition immediately postoperatively. One group (A) received a composition of 4 LAB and 4 fibers, and another group (B) received placebo (fibers only) starting the day before surgery and continuing for 8 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, noninfectious complications, and side effects were recorded. RESULTS: The incidence of postoperative bacterial infections was significantly lower with LAB and fibers (12.5%) than with fibers only (40%). In addition, the duration of antibiotic therapy was significantly shorter in the latter group. Fibers and LAB were well tolerated. CONCLUSION: Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates and antibiotic therapy following PPPD.

Pretreatment with pro- and synbiotics reduces peritonitis-induced acute lung injury in rats.

BACKGROUND: To study whether enteral pretreatment with a synbiotic composition of lactic acid bacteria and bioactive fibers can reduce peritonitis-induced lung neutrophil infiltration and tissue injury in rats. MATERIALS AND METHODS: Rats were divided into five groups, and subjected to induction of peritonitis-induced lung injury using a cecal ligation and puncture model (CLP). All animals were pretreated for 3 weeks prior the CLP by daily gavage with either (1) a synbiotic composition (10(10) CFU of Pediococcus pentosaceus 5-33:3, 10(10) CFU of Leuconostoc mesenteroides 77:1, 10(10) CFU of L. paracasei subspecies paracasei, 10(10) CFU of L. plantarum 2362 plus fermentable fibers), (2) fermentable fibers alone, (3) nonfermentable fibers, (4) a probiotic composition (10(10) CFU of P. pentosaceus 5-33:3, 10(10) CFU of L. mesenteroides 77:1, 10(10) CFU of L. paracasei subsp. paracasei, 10(10) CFU of L. plantarum 2,362), or (5) a heat-killed probiotic composition. All animals were killed 24 hours after CLP and lung tissue samples were studied for degree of neutrophil infiltration and levels of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta. In addition the lung wet-to-dry tissue weight ratio, the myeloperoxidase activity, and malondialdehyde content were also assessed. RESULTS: No mortality was encountered in any of the groups. Histologic signs of lung injury (number of neutrophils and TNF-alpha, IL-1beta staining) were observed in all groups except the synbiotic and probiotic treated groups. Myeloperoxidase activity and malondialdehyde content were significantly lower in the two lactobacillus- pretreated groups, with no difference between them. Heavy infiltration of lung tissue with neutrophils was observed only in fiber-treated (302.20 +/- 7.92) and placebo-treated (266.90 +/- 8.92) animals. This was totally abolished in the synbiotic-treated group (34.40 +/- 2.49). Lung edema (wet-to-dry lung weight ratio) was significantly reduced in the synbiotic-treated group (4.92 +/- 0.13 vs. 5.07 +/- 0.08 and 5.39 +/- 0.10, respectively). CONCLUSION: Three weeks of preoperative enteral administration of a synbiotic composition reduced peritonitis-induced acute lung injury in rats in a CLP model.

Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease.

Complications of Crohn's disease (CD) lead to surgery in about 70-90% of patients. The majority of patients suffer from relapse of the disease. Colonic bacteria are essential to the development of CD. Therefore, a rationale exists in trying to prevent relapse by manipulation of gut microflora. This is feasible by treatment with probiotics or antibiotics. Synbiotic 2000 is a cocktail containing 4 probiotic species and 4 prebiotics. It is rational to pursue that it could be effective in preventing postoperative disease. We sought to check weather treatment with Synbiotic 2000 could prevent postoperative recurrence in patients with CD. This was a prospective multicenter, randomized study. Patients were randomized to active treatment or placebo in a 2:1 ratio. Follow-up consisted of endoscopic, clinical, and laboratory parameters. Thirty patients were enrolled. No differences were found between the 2 treatment groups regarding gender, age at diagnosis, age at surgery, weight, smoking status, type of disease, length of the resected segment, or medical treatment prior to surgery. No difference in either endoscopic or clinical relapse rate was found between patients treated with once daily dose of Synbiotic 2000 or placebo. In our small study, Synbiotic 2000 had no effect on postoperative recurrence of patients with CD. Larger studies in patients with the inflammatory type of CD undergoing surgery, using higher doses of probiotics cocktail might prove effective.

Comparative study of the intestinal mucus barrier in normal and inflamed colon.

AIM: To study the role of mucus in the spatial separation of intestinal bacteria from mucosa. PATIENTS AND METHODS: Mucus barrier characteristics were evaluated using histological material obtained by biopsy from purged colon, colon prepared with enema and material from untreated appendices fixed with non-aqueous Carnoy solution. Bacteria were evaluated using fluorescence in situ hybridization, with bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue stain. Biopsies from controls (n = 20), patients with self-limiting colitis (SLC; n = 20), ulcerative colitis (n = 20) and 60 randomly selected appendices were investigated. RESULTS: The mucosal surface beneath the mucus layer was free of bacteria in > or =80% of the normal appendices and biopsies from controls. The thickness of the mucus layer and its spread decreased with increasing severity of the inflammation; the epithelial surface showed bacterial adherence, epithelial tissue defects and deep mucosal infiltration with bacteria and leucocytes. Bacteria and leucocytes were found within mucus in all biopsy specimens from patients with ulcerative colitis, SLC, and acute appendicitis. The concentration of bacteria within mucus was inversely correlated to the numbers of leucocytes. CONCLUSIONS: The large bowel mucus layer effectively prevents contact between the highly concentrated luminal bacteria and the epithelial cells in all parts of the normal colon. Colonic inflammation is always accompanied by breaks in the mucus barrier. Although the inflammatory response gradually reduces the number of bacteria in mucus and faeces, the inflammation itself is not capable of preventing bacterial migration, adherence to and invasion of the mucosa.

Aggressive management of surgical emergencies.

Increasing evidence suggests that two factors significantly influence outcome in a surgical emergency - premorbid health and the degree of inflammation during the first 24 h following trauma. Repeat observations suggest that the depth of post-trauma immunoparalysis reflects the height of early inflammatory response. Administration to surgical emergencies, as was routine in the past, of larger amounts of fluid and electrolytes, fat, sugar and nutrients seems counterproductive as it increases immune dysfunction, impairs resistance to disease and, in fact, increases morbidity. Instead, strong efforts should be made to limit the obvious superinflammation, which occurs during the first 24 h after trauma and, thereby, reduce the subsequent immunoparalysis. Several approaches show efficacy in limiting early superinflammation such as strict control of blood glucose, avoidance of stored blood when possible, supply of antioxidants, live lactic acid bacteria and plant fibres. This review focuses mainly on use of live lactic acid bacteria and plant fibres, often called synbiotics. Encouraging experience is reported from clinical trials in liver transplantation, severe pancreatitis and extensive trauma. Immediate control of inflammation by enteral nutrition and supply of antioxidants, lactic acid bacteria and fibres is facilitated by feeding tubes, introduced as early as possible on arrival at the hospital.

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.

Impact of nutrition on ageing and disease.

PURPOSE OF REVIEW: The globe is suffering a tsunami of chronic diseases, affecting especially the elderly and those with a dysfunctioning immune system. The fundamental principles of optimal health and optimal ageing are abstaining from smoking, modest alcohol consumption, regular physical exercise and a diet rich in fish and plants and low in condensed calories, sugar and dairy products. RECENT FINDINGS: Dietary supply and production of advanced glycation end products leads to the accumulation of these products in the tissues and is strongly associated with ageing of the vascular endothelium, nervous system, eyes and other vital organs. Telomeres, which are not involved in DNA repair, remain unrepaired and loose with time. A decline in innate and acquired immunity is seen with increasing age and maintenance of low basal immune activity (degree of inflammation) seems important for health and longevity: 'people who are predisposed to weak inflammatory activity may live longer'. SUMMARY: Supplementation with vitamins has little effect on ageing/prevention of chronic diseases, but antiinflammatory molecules like polyphenols are more effective, especially when combined with reduced intake of calorie-condensed foods. The effect of probiotics on ageing needs further exploration. The effects of caloric restriction, proven effective in other species to control aging and prolong lifespan, have not been fully explored in humans.

Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation--a randomized, double-blind trial.

Bacterial infections frequently occur early after liver transplantation. We recently reported significant progress with a synbiotic composition, consisting of one lactic acid bacteria (LAB) and one fiber, which reduced the infection rate from 48% (with selective bowel decontamination) to 13%. Now, our aim is to study if a combination of different LAB and fibers would further improve outcome. A prospective randomized double-blind trial was undertaken in 66 liver transplant recipients. All patients received enteral nutrition immediately post-operatively. Comparison was made between one group (A) receiving a composition of four LAB and four fibers and another group (B) receiving the fibers only. The treatment started the day before surgery and continued for 14 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, non-infectious complications and side effects of enteral nutrition were recorded. The incidence of post-operative bacterial infections was significantly reduced; being 48% with only fibers and 3% with LAB and fibers. In addition, the duration of antibiotic therapy was significantly shorter in the latter group. In both groups, mainly mild or moderate infections occurred. Fibers and LAB were well tolerated. Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates following liver transplantation. Treatment with only fibers led to a low incidence of severe infections.