Effects of Synbiotic2000™ Forte on the Intestinal Motility and Interstitial Cells of Cajal in TBI Mouse Model.

The main objective of this study was to investigate the effects of Synbiotic2000™ Forte on the intestinal motility and interstitial cells of Cajal (ICC) in traumatic brain injury (TBI) mouse model. Kunming mice were randomly divided into sham operation group (S group), enteral nutrition group with TBI (E group), and Synbiotic2000™ Forte group with TBI (P group). The contractile activity of the intestinal smooth muscle, densities and ultrastructure of the ICC, kit protein concentration, weight, and defecation of mice were monitored and analyzed. TBI markedly suppressed contractile activity of the intestinal smooth muscle (P < 0.01), which led to a reduction of defecation (P < 0.01) and weight (P < 0.01). However, application of Synbiotic2000™ Forte significantly improved contractile activity of the small intestine (P < 0.01), which may be related to protective effects to the interstitial cells of Cajal, smooth muscle cells, and enteric neurons. TBI impaired ICC networks and densities (P < 0.01), events that were protected by the application of Synbiotic2000™ Forte. Synbiotic2000™ Forte may attenuate TBI-mediated inhibition of the kit protein pathway. Synbiotic2000™ Forte may improve intestinal motility and protect the ICC in the TBI mouse. These findings provide a novel support for the application of Synbiotic2000™ Forte in intestinal motility disturbance after TBI.

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.

Gut microbiota, immune development and function.

The microbiota of Westerners is significantly reduced in comparison to rural individuals living a similar lifestyle to our Paleolithic forefathers but also to that of other free-living primates such as the chimpanzee. The great majority of ingredients in the industrially produced foods consumed in the West are absorbed in the upper part of small intestine and thus of limited benefit to the microbiota. Lack of proper nutrition for microbiota is a major factor under-pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation, and the production and leakage of endotoxins through the various tissue barriers. Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced intake of fruit and vegetables, are key factors behind the commonly observed elevated inflammation and the endemic of obesity and chronic diseases, factors which are also likely to be detrimental to microbiota. As a consequence of this lifestyle and the associated eating habits, most barriers, including the gut, the airways, the skin, the oral cavity, the vagina, the placenta, the blood-brain barrier, etc., are increasingly permeable. Attempts to recondition these barriers through the use of so called 'probiotics', normally applied to the gut, are rarely successful, and sometimes fail, as they are usually applied as adjunctive treatments, e.g. in parallel with heavy pharmaceutical treatment, not rarely consisting in antibiotics and chemotherapy. It is increasingly observed that the majority of pharmaceutical drugs, even those believed to have minimal adverse effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely affect immune development and functions and are most likely also deleterious to microbiota. Equally, it appears that probiotic treatment is not compatible with pharmacological treatments. Eco-biological treatments, with plant-derived substances, or phytochemicals, e.g. curcumin and resveratrol, and pre-, pro- and syn-biotics offers similar effects as use of biologicals, although milder but also free from adverse effects. Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases. Pharmaceutical treatment has, thus far, failed to inhibit the tsunami of endemic diseases spreading around the world, and no new tools are in sight. Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, seem to be the only alternatives with the potential to control the present escalating crisis. The present review focuses on human studies, especially those of clinical relevance.

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.

Integrative medicine and human health - the role of pre-, pro- and synbiotics.

Western lifestyle is associated with a sustained low grade increase in inflammation -increased levels of endotoxin in the body and increased activation of Toll-like receptors and neutrophils, which leads to impaired immunity and reduced resistance to disease, changes which might explain the epidemic of chronic diseases spreading around the globe. The immune system cannot function properly without access to bacteria and raw plants, rich not only in bacteria but also in plant fibre, antioxidants, healthy fats and numerous other nutrients. Modern food technology with plant breeding, separation, condensation of food ingredients, heating, freezing, drying, irradiation, microwaving, are effective tool to counteract optimal immune function, and suspected to be a leading cause of so called Western diseases. Supply of pre-, pro-, and synbiotics have sometimes proved to be effective tools to counteract, especially acute diseases, but have often failed, especially in chronic diseases. Thousands of factors contribute to unhealth and numerous alterations in life style and food habits are often needed, in order to prevent and cure "treatment-resistant" chronic diseases. Such alterations include avoiding processed foods rich in pro-inflammatory molecules, but also a focus on consuming substantial amounts of foods with documented anti-inflammatory effects, often raw and fresh green vegetables and tubers such as turmeric/curcumin.

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection.

The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.

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.

Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research.

Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. There is a growing interest in probiotics within the scientific community, with consumers, and in the food industry. The interactions between the gut and intestinal microbiota and between resident and transient microbiota define a new arena in physiology, an understanding of which would shed light on the "cross-talk" between humans and microbes. The different beneficial effects of specific probiotic strains may be translated into different health claims. However, there is a need for comprehensive and harmonized guidelines on the assessment of the characteristics and efficacy of probiotics and of foods containing them. An international expert group of ILSI has evaluated the published evidence of the functionality of different probiotics in 4 areas of (human) application: 1) metabolism, 2) chronic intestinal inflammatory and functional disorders, 3) infections, and 4) allergy. Based on the existing evidence, concrete examples of demonstration of benefits and gaps are listed, and guidelines and recommendations are defined that should help design the next generation of probiotic studies.

Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome.

Ulcerative colitis and Crohn's disease, the 2 distinct idiopathic pathologies of inflammatory bowel diseases, are spontaneously relapsing, immunologically mediated disorders of the gastrointestinal tract. Selected probiotics strains have been proven to be clinically effective in maintaining remission in patients with ulcerative colitis. None of the probiotics thus far tested has been shown to be effective in induction of remission or in maintenance of remission in patients with Crohn's disease. The multispecies probiotics mixture of 8 strains seems effective in the maintenance of remission in pouchitis. Irritable bowel syndrome is a functional bowel disorder manifested by chronic, recurring abdominal pain or discomfort associated with disturbed bowel habit in the absence of structural abnormalities likely to account for these symptoms. Recently conducted appropriately powered studies with different (combinations of) probiotics show positive results on reduction of symptoms, although a considerable placebo effect is also found. Mechanistic studies aimed at pathophysiological mechanisms of inflammatory bowel diseases can identify new targets for probiotic bacteria.

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.

Pro- and synbiotics to control inflammation and infection in patients with multiple injuries.

BACKGROUND: A recent randomized clinical trial of our group disclosed considerable reduction of the infective sequelae after administration of a synbiotic formula, namely Synbiotic 2000FORTE, in patients with multiple injuries, the latter being a preparation of four probiotics. The mechanism of action of synbiotics was studied. METHODS: A total of 72 patients with severe multiple injuries were allocated to a 15-day administration of either placebo or the synbiotic formula. The association of bloodstream infections, ventilator-associated pneumonia (VAP), serum levels of C-reactive protein (CRP), and endotoxins (LPS) were studied. RESULTS: Sepsis in the field of bacteremia occurred in 13 patients treated with placebo (36.1%) compared with 5 patients treated with Synbiotic 2000FORTE (13.9%, p = 0.028 between groups). The time to progression to primary bacteremia was longer among patients treated with Synbiotic 2000FORTE compared with placebo (p = 0.0237 between groups). Twelve (33.3%) and five (13.9%) placebo-treated and probiotic-treated patients, respectively, developed ventilator-associated pneumonia with Acinetobacter baumannii as a bacterial cause (p = 0.047 between groups). Treatment with synbiotics was accompanied by reduction of white blood cell counts and LPS and CRP levels in either patients who did or did not develop sepsis. CONCLUSIONS: Synbiotics contained in the studied formula decrease significantly the risk for sepsis by bloodstream infections and the occurrence of VAP by A. baumannii. The mechanisms of action might involve direct immunomodulatory effect, prevention of bacterial translocation, or most likely a combination of both.

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.

Bio-ecological control of chronic liver disease and encephalopathy.

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and in one study also evidence of clinical improvement.