Absorption Of Endotoxin Research Articles

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.

Surgical Parameters Related to Excessive Intrarenal Pressure during Minimally Invasive Percutaneous Nephrolithotomy in the Supine Position: A Prospective Observational Clinical Study.

Objective Excessive intrarenal pressure (IRP) during surgery for renal stones is related to postoperative complications due to systemic absorption of bacteria and endotoxins. This study is aimed at evaluating factors that induce excessive IRP in minimally invasive percutaneous lithotripsy (mini-PCNL) in the supine position. Methods 27 patients underwent mini-PCNL for intrarenal stones under supine position and were analyzed in this study. The IRP changes were measured at the phases of “baseline,” “table tilting,” “upper-pole navigation,” “stone fragmentation,” and “vacuum cleaning effect.” The relationship between the mean IRP and cumulative time of IRP ≥ 30 cmH2O was analyzed by according to the surgical parameters. Multiple regression analysis showed the effect of the surgical parameters on postoperative fever-related IRP elevation. Results Mean age was 59.3 ± 14.6 years. The mean stone burden was 24.6 ± 8.1 mm3. IRP was higher than baseline (31.6 ± 12.1) during upper-pole navigation (60.0 ± 22.9, p = 0.003) and stone fragmentation (46.2 ± 9.9, p < 0.001). The subgroup's IRP baseline < 20 cmH2O significantly increased during the upper-pole navigation. Changes in IRP at each stage were affected by baseline IRP (p < 0.001), operation methods (p = 0.021), number of calyces with stones (p = 0.034), and laser energy of Joules (p = 0.041) and frequency (p = 0.038). Conclusion In supine mini-PCNL, the IRP was higher during laser fragmentation and upper-pole navigation. The table tilting procedure can be helpful in selected patients. The vacuum cleaner effect did not affect IRP.

A cell‐based approach to quantifying endotoxin in human plasma samples

Poor dietary choices are thought to contribute to the risk of developing a variety of chronic diseases, in part, through promoting a state of low‐grade inflammation. For example, there are multiple research reports indicating that high‐fat meals promote a transient post‐prandial inflammatory state. Several investigators have hypothesized that high fat meals promote the absorption of microbial endotoxin across the gut wall and that once in the circulation this promotes inflammation through the activation of TLR4 signaling pathway on circulating innate immune cells (e.g., monocytes). Direct assessment of endotoxin in human blood samples is problematic. Reliance on the limulus amebocyte lysate (LAL) test for quantifying endotoxin in a protein‐rich matrix, such as human plasma, requires that samples be heated prior to the analyses. Recovery of endotoxin spiked into plasma samples prior to heating is remarkably low, typically less than 1%. This phenomena, commonly referred to as neutralization, raises grave doubts about the suitability of the LAL test for quantifying endotoxin in the human circulation. Many researchers have long recognized the need for a more robust and accurate method for quantifying low levels of endotoxin in human circulation. In 1995, a cell‐based bioassay approach referred to as monocyte activation test (MAT) was developed and marketed as an alternative to LAL test. Unfortunately, the MAT requires that blood samples are processed within a few hours of collection, which greatly limits the utility of this alternative approach. We have developed and tested a cell‐based bioassay (CBA) for quantifying endotoxin in human plasma following storage at −80°C by using THP‐1 cells (i.e., a human monocytic cell line) stably‐transfected with a luciferase reporter driven by multiple NF‐kB promoters. Our CBA provides reliable and reproducible quantitation of endotoxin in unheated human plasma samples with a limit of detection approaching 0.05 endotoxin units (EU)/mL of plasma. Sensitivity and precision of our CBA compares well with the performance of a recently released commercial cell line (InvivoGen). In conclusion, both of these CBAs appear to provide the research community with a reliable alternative to the LAL test for quantifying endotoxin in human plasma.Support or Funding InformationThis research was supported in part by Grant Number P50AT006273 from the National Center for Complementary and Integrative Health (NCCIH), the Office of Dietary Supplements(ODS), and the National Cancer Institute (NCI). Additional funding was provided by the Food‐for‐the‐21st Century Program ‐Nutrition Cluster, which is part of the College of Agriculture, Food and Natural Resources at the University of Missouri ‐ Columbia. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NCCIH, ODS, NCI, or the National Institutes of Health.

Safety and efficacy of self-assembling bubble carriers stabilized with sodium dodecyl sulfate for oral delivery of therapeutic proteins

Sodium dodecyl sulfate (SDS) is generally regarded as a potent permeability enhancer in oral formulations; however, one concern related to the use of any permeation enhancer is its possible absorption of unwanted toxins during the period of epithelial permeability enhancement. In this work, the safety and efficacy of an SDS-containing bubble carrier system that is developed from an orally administered enteric-coated capsule are evaluated. The bubble carriers comprise diethylene triamine pentaacetic acid (DTPA) dianhydride, sodium bicarbonate (SBC), SDS, and insulin. Upon exposure to the intestinal fluid, DTPA dianhydride hydrolyzes to yield acids, and SBC rapidly reacts with these acids to generate CO2, producing bubble carriers, each containing a self-assembling water film. The hydrophilic insulin is entrapped in the self-assembled water film, which is stabilized by SDS. The SDS in the bubble carrier system can act as a dissolution enhancer in the dispersion of insulin molecules, as a surfactant that stabilizes the bubble carriers, as a protease inhibitor that protects the protein drug, and as a permeation enhancer that augments its oral bioavailability. Hence, a significant increase in the plasma insulin level and an excellent blood glucose-lowering response in diabetic rats are effectively achieved. Moreover, the enhancement of epithelial permeation by this SDS-containing formulation does not promote the absorption of intestinal endotoxins. The above facts indicate that the bubble carrier system that is stabilized by SDS can be used as a safe and potent carrier in the oral delivery of therapeutic proteins.

Yeast Culture and Vitamin E Supplementation Alleviates Heat Stress in Dairy Goats.

This study was conducted to determine and compare the effects of yeast yeast culture (YC) and vitamin E (VE) supplementation on endotoxin absorption and antioxidant status in lactating dairy goats suffering from heat stress (HS). Three first lactation Saanen dairy goats (body weight 30±1.5 kg) were surgically fitted with indwelling catheters in the portal vein, mesenteric vein and carotid artery, and were randomly assigned to a 3×3 Latin square design. Dietary treatments were the basal diet, and the basal diet supplemented with either 100 IU VE or 30 g YC. Goats were kept in temperature and humidity-controlled room at 35°C from 8:00 to 20:00 and at 24°C from 20:00 till the next morning at 8:00. The relative humidity was kept at 55%. HS increased dairy goats’ rectum temperature and respiration frequency (p<0.01). HS reduced plasma flux rate of milk goats (p<0.01), but the plasma flux rate increased when the animal was under the conditions of the thermo-neutral period (p<0.01). The VE supplementation lowered dairy goats’ rectum temperature during thermo-neutral period (p<0.01). Meanwhile, no significant differences were observed between the control and YC treatment in rectum temperature and respiration frequency (p>0.05). Dietary supplementation of VE and YC reduced heat stressed dairy goats’ endotoxin concentration of the carotid artery and portal vein (p<0.01). However, the endotoxin concentration of the YC treatment was higher than that of the VE treatment (p<0.01). Both VE and YC supplementation decreased heat stressed dairy goats’ absorption of endotoxin in portal vein (p<0.01). The endotoxin absorption of YC treatment was higher than the VE treatment (p<0.01). The addition of VE and YC decreased dairy goats’ superoxide dismutase (SOD) concentration during HS and the whole experiment period (p<0.01). The addition of VE lowered SOD concentration during thermo-neutral period (p<0.01). Likewise, the addition of VE and YC lowered dairy goats’ malonaldehyde (MDA) concentration during HS and the whole experimental period, and the MDA concentration in the VE treatment was lower than the YC treatment (p<0.05). The addition of VE decreased MDA concentration during thermo-neutral period. On the contrast, the addition of VE increased dairy goats total antioxidant potential (TAP) concentration during HS, thermo-neutral and the whole experimental period (p<0.01). The addition of YC increased TAP concentration only during HS period (p<0.01). It is concluded that both VE and YC are useful in alleviating HS of dairy goats by weakening endotoxin absorption and promoting antioxidant capacity. Compared with YC, VE is much more powerful in easing dairy goats HS.

Gut Inflammation in Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis-Contrasting Pattern of Liver-gut Cross Talk

Gut Inflammation in Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis-Contrasting Pattern of Liver-gut Cross Talk

015 PROGNOSTIC SIGNIFICANCE OF PLASMA CONCENTRATIONS OF PROCALCITONIN IN PATIENTS WITH SUSPECTED HEART FAILURE

Background Heart failure is associated with an increase in plasma concentrations of markers of inflammation and fibrosis. Some have hypothesised that this may reflect absorption of endotoxins from gut bacteria or bacterial translocation into the gut wall. This might provoke an increase in markers of infection, such as procalcitonin (PCT). Methods Patients with suspected heart failure referred from the local community to a specialist clinic were invited to participate. Consenting patients underwent a systematic evaluation including prior medical history, medications, symptoms, signs, electro- and echocardiograms, standard haematology and biochemistry profiles and measurement of PCT and amino-terminal pro-brain natriuretic peptide (NT-proBNP). Results Of 1891 patients enrolled, the median age was 72 years (IQR 64–78), 669 were women, 807 had left ventricular systolic dysfunction (LVSD), 400 had no major echocardiographic abnormalities other than LVSD, 192 had no major echo abnormality but an NT-proBNP >400 ng/l (of whom 65 had atrial fibrillation and 15 had eGFR Conclusions PCT is similarly elevated in all heart failure phenotypes studied and adds prognostic information to standard variables. Whether it is just a marker of risk or sits on an important pathway driving the progression of heart failure awaits further study.

Intestinal alkaline phosphatase prevents metabolic syndrome in mice

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.

Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins

Recently, we reported a pH-responsive nanoparticle (NP) system shelled with chitosan (CS), which could effectively increase the oral absorption of insulin and produce a hypoglycemic effect, presumably due to the CS-mediated tight junction (TJ) opening. It has been often questioned whether CS can also enhance the absorption of endotoxins present in the small intestine. To address this concern, we studied the effect of CS NPs on the absorption of lipopolysaccharide (LPS), the most commonly found toxin in the gastrointestinal tract. To follow their biodistribution by the single-photon emission computed tomography/computed tomography, LPS and insulin were labeled with 99mTc-pertechnetate ( 99mTc-LPS) and 123iodine ( 123I-insulin), respectively. The 99mTc-LPS was ingested 1 h prior to the administration of the 123I-insulin-loaded NPs to mimic the physiological conditions. The confocal and TEM micrographs show that the orally administered CS NPs were able to adhere and infiltrate through the mucus layer, approach the epithelial cells and mediate to open their TJs. The radioactivity associated with LPS was mainly restricted to the gastrointestinal tract, whereas 123I-insulin started to appear in the urinary bladder at 3 h post administration. This observation indicates that the insulin-loaded in CS NPs can traverse across the intestinal epithelium and enter the systemic circulation, whereas LPS was unable to do so, probably because of the charge repulsion between the anionic LPS in the form of micelles and the negatively charged mucus layer. Our in vivo toxicity study further confirms that the enhancement of paracellular permeation by CS NPs did not promote the absorption of LPS. These results suggest that CS NPs can be used as a safe carrier for oral delivery of protein drugs.

Effect of heat stress on endotoxin flux across mesenteric-drained and portal-drained viscera of dairy goat

This study was designed to evaluate the effect of heat stress on endotoxin flux across mesenteric-drained and portal-drained viscera of dairy goats. Three Saanen first lactation dairy goats were surgically fitted with indwelling catheters in the portal vein, the mesenteric vein and carotid, and were kept in thermal-neutral and then heat stress environment, for examining the effect of heat stress on endotoxin absorption and redox status. Average net absorption of endotoxin (EU/h) across mesenteric-drained viscera (MDV) and portal-drained viscera (PDV) during the whole period of heat stress increased by 279.05% and 227.92% in relation to thermo-neutral period. Plasma concentration of glutathione peroxidase (GSH-Px) and catalase (CAT) in mesenteric and portal vein, and that of superoxide dismutase (SOD) in mesenteric vein, increased significantly during heat stress. Main conclusions were: (i) net absorption of endotoxin in portal vein is mainly from non-mesenteric tissues both in heat stress and in thermo-neutral condition; (ii) heat stress may lead to the significant decrease in plasma SOD, GSH-Px, CAT flux across PDV and MDV, and the significant increase in endotoxin flux across PDV and MDV; and (iii) the increase in gastrointestinal permeability in dairy goats during heat stress may not be induced by the increase in oxidative stress.

Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation

Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation

Low-grade inflammation is a risk factor for the onset of atherosclerosis. Little is known about the involvement of endotoxin absorption from the gut during the digestion of lipids. In the present study, we first investigated in humans the impact of a mixed meal containing dispersed lipids on postprandial endotoxemia and inflammation. We then investigated the effect of (i) oil emulsification in vivo in rats and (ii) fatty acid amounts in vitro using Caco-2 cells on postprandial endotoxemia. In humans, postprandial endotoxemia increased early after the meal. Moreover, we evidenced that the endotoxin receptor sCD14 increased during digestion and that chylomicrons could contribute to absorbed endotoxin transport. This could explain the significant peak of inflammatory cytokine IL-6 that we observed 2 h after the mixed meal. Interestingly, in rats, the emulsion led to both higher endotoxemia and hypertriglyceridemia than oil and compared to a control saline load. In vitro, incubation of Caco-2 cells with increasing fatty acid concentrations enhanced epithelial absorption of endotoxin. To our knowledge, this is the first study evidencing in healthy humans that, following a mixed meal containing lipids, increased endotoxemia is associated with raised sCD14 and a peak of IL-6. On a repeated basis, this may thus be a triggering cascade for the onset of atherosclerosis. In this respect, optimizing both dietary fat amount and structure could be a possible strategy to limit such low-grade endotoxemia and inflammation by the control of postprandial lipemia.

Effect rhubarb retention enema for renal dysfunction after traumatic brain injury treatment

Objective Observation of rhubarb retention enema for renal dysfunction after traumatic brain injury treatment.Methods Randomly after 60 cases of traumatic brain injury patients with renal dysfunction were divided into 2 groups: treatment group (rhubarb retention enema group, 32 cases)! Control group (Western non-dialysis method of treatment group , 28 cases).Through different treatment on the Evaluation of group 2 patients.Results Rhubarb retention enema group therapy seven days later, according to the standard to determine efficacy of the two experimental group was significantly more effective than the control group(P < 0.05).Conclusions Rhubarb retention enema for renal dysfunction after traumatic brain injury have positive efect, they not only can reduce the blood BUN Cr content, improve clinical symptoms and reduce mortality. But also has its own Tongfu reduce the absorption of endotoxin, is a simple, effective the exact method of treatment. Key words: Traumatic brain injury; Renal dysfunction; Retention enema; Rhubarb

Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis

The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml range, activating p38 MAP kinase and releasing serotonin (5-HT) and thromboxane. The objectives of this study were firstly to determine whether endotoxin and platelet activation could be measured in the plasma of horses in the developmental phase of laminitis induced with oligofructose. Secondly, the time course of events involving platelet activation and platelet-derived vasoactive mediator production was investigated. Laminitis was induced in six Standardbred horses by the administration of 10 g/kg bwt of oligofructose. Plasma samples were obtained every 4 h, and platelet pellets were obtained by centrifugation. LPS was measured using a kinetic limulus amebocyte lysate assay, and platelet activation was assessed by Western blotting for the phosphorylated form of p38 MAP kinase. Plasma 5-HT was assayed by HPLC with electrochemical detection and thromboxane B 2 was measured by radioimmunoassay. Clinical signs of laminitis and histopathologic changes were observed in lamellar sections from five of the six horses. Onset of lameness was between 20 and 30 h after the administration of oligofructose. LPS increased above the limit of detection (0.6 pg/ml) to reach a peak of 2.4 ± 1.0 pg/ml at 8 h. TNFα was also detectable in the plasma from 12 to 24 h. There was a time-dependent increase in platelet p38 MAPK phosphorylation, which peaked at approximately 12 h (3.8 ± 1.3 fold increase); plasma 5-HT and thromboxane increased steadily after this time (2.9 ± 0.6 and 11.3 ± 5.0 fold increases, respectively). These data indicate that small quantities of endotoxin may move into the circulation from the large intestine after the sharp decrease in pH that occurs as a result of carbohydrate fermentation. Correlating these findings with in vitro studies suggests that LPS may primarily activate platelets, leading indirectly to the activation of leukocytes. Therefore, endotoxin may contribute in the initiation of the early inflammatory changes observed in experimental models of acute laminitis.

Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine

Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated.

Long-term ethanol feeding enhances susceptibility of the liver to orally administered lipopolysaccharides in rats.

Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. However, it is still unclear how long-term ethanol feeding affects absorption of endotoxin from the intestine and susceptibility of the liver to gut-derived endotoxin. The object of this study was to determine the effect of long-term ethanol feeding on hepatic susceptibility to orally administered endotoxin. Male Wistar rats that weighed approximately 150 g were pair-fed with an ethanol-containing liquid diet or a control diet for 35 days. In some experiments, 0, 10, or 20 mg/kg of lipopolysaccharides (LPS) was added to the liquid diet for 7 days beginning on day 29. On day 36, the animals were killed for blood biochemistry and histologic examination of the liver. We also determined plasma endotoxin levels after 20 mg/kg of LPS administration using a gastric tube. In another set of experiments, we determined intestinal permeability using FD4 (fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4000 D). With 10 mg/kg of LPS, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were significantly increased in the ethanol-fed rats but not in controls. After 20 mg/kg of LPS administration, more substantial increases in serum ALT and ALP levels were observed in ethanol-fed rats as compared with control diet-fed rats. Plasma endotoxin levels in long-term ethanol-fed rats were higher than those in control rats after intragastric administration of high-dose endotoxin (20 mg/kg). Furthermore, intestinal permeability to FD4 was increased by long-term ethanol administration. Long-term ethanol feeding increases intestinal permeability to and absorption of endotoxin, which can sequentially enhance hepatic susceptibility to orally administered endotoxin. This model has potential as a subclinical experimental model for the study of alcoholic liver disease.

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?†‡§

Increased gastrointestinal permeability has been demonstrated in several liver diseases. It may facilitate the absorption of gut-derived endotoxin-stimulating Kupffer cells to release proinflammatory cytokines or other potentially hepatotoxic compounds. We examined gastrointestinal permeability, plasma levels of anti-lipopolysacharides (anti-LPS), and four proinflammatory cytokines in 20 patients with intrahepatic cholestasis of pregnancy (ICP) compared with 22 normal pregnant and 29 non-pregnant women. Urinary excretion of sucrose and the urinary lactulose/mannitol (L/M) ratio after a standard oral load were used to assess gastrointestinal permeability. Anti-LPS (IgA, IgM, and IgG) were measured in peripheral blood by Human EndoCAb test kit; TNF-alpha, IL-1beta, IL-6, and IL-10 by Quantikine HS human immunoassays. Sucrose urinary excretion was similar in the three groups, indicating normal gastric permeability. The urinary L/M ratio was significantly higher in ICP than in the other groups [median (interquartile range): 0.018% (0.011-0.023) in ICP, 0.012% (0.009-0.016) in normal pregnancies, and 0.009% (0.008-0.012) in non-pregnant women, P < .01]. No significant differences were found in anti-LPS or cytokines plasma levels except slightly higher levels of IL-6 in ICP patients than in non-pregnant women (P < .05). Four of five women with abnormal urinary L/M ratio during ICP continued to show abnormalities in tests up to 2 years after delivery. In conclusion, an increased intestinal permeability was detected in ICP patients during and after pregnancy. A "leaky gut" may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxin and the enterohepatic circulation of cholestatic metabolites of sex hormones and bile salts.

Bacterial translocation: impact of probiotics

There is a considerable amount of data in humans showing that patients who cannot take in nutrients enterally have more organ failure in the intensive care unit, a less favourable prognosis, and a higher frequency of septicaemia, in particular involving bacterial species from the intestinal tract. However, there is little evidence that this is connected with translocation of bacterial species in humans. Animal data more uniformly imply the existence of such a connection. The main focus of this review is to describe different ways to alter the luminal milieu to decrease bacterial translocation. It is possible to reduce absorption of endotoxin by administration of bile salts in obstructive jaundice. Increasing the oral intake of glutamine will reduce bacterial translocation in rats with radiation-induced gut injury. The bacterial microflora plays a very important role in maintaining the normal intestinal ecological environment and supplying preferred fuels to the in testinal wall, consequently supporting the intestinal barrier. Disruption of the balance of intestinal bacterial microflora may increase the incidence of bacterial translocation by modifying intestinal barrier function. Bacterial species such as enteric Gram-negatives and Gram-positive cocci are more prone to translocation, whereas lactobacilli seem to have a protective effect. Administration of live lactobacilli either orally or by enema will reduce translocation. The mechanisms underlying the decreased translocation are not obvious. One effect may be mediated via an action on the intestinal wall and its permeability. Recently, the results of three randomized studies on the use of L. plantarum in patients with pancreatitis, undergoing liver transplantation or upper gastrointestinal surgery have been published, which all indicate a potential role for lactobacilli in translocation. In conclusion, by altering the luminal content of bacteria it seems possible to reduce the inci d ence of secondary infections. The influence of the luminal milieu on bacterial translocation is not fully understood. There is convincing evidence from experimental studies, but only circumstantial evidence from clinical studies. Keywords: Bacterial translocation; barrier function; lactobacilli; probiotics.

Bacterial translocation: impact of probiotics

There is a considerable amount of data in humans showing that patients who cannot take in nutrients enterally have more organ failure in the intensive care unit, a less favourable prognosis, and a higher frequency of septicaemia, in particular involving bacterial species from the intestinal tract. However, there is little evidence that this is connected with translocation of bacterial species in humans. Animal data more uniformly imply the existence of such a connection. The main focus of this review is to describe different ways to alter the luminal milieu to decrease bacterial translocation. It is possible to reduce absorption of endotoxin by administration of bile salts in obstructive jaundice. Increasing the oral intake of glutamine will reduce bacterial translocation in rats with radiation-induced gut injury. The bacterial microflora plays a very important role in maintaining the normal intestinal ecological environment and supplying preferred fuels to the in testinal wall, consequently supporting the intestinal barrier. Disruption of the balance of intestinal bacterial microflora may increase the incidence of bacterial translocation by modifying intestinal barrier function. Bacterial species such as enteric Gram-negatives and Gram-positive cocci are more prone to translocation, whereas lactobacilli seem to have a protective effect. Administration of live lactobacilli either orally or by enema will reduce translocation. The mechanisms underlying the decreased translocation are not obvious. One effect may be mediated via an action on the intestinal wall and its permeability. Recently, the results of three randomized studies on the use of L. plantarum in patients with pancreatitis, undergoing liver transplantation or upper gastrointestinal surgery have been published, which all indicate a potential role for lactobacilli in translocation. In conclusion, by altering the luminal content of bacteria it seems possible to reduce the inci d ence of secondary infections. The influence of the luminal milieu on bacterial translocation is not fully understood. There is convincing evidence from experimental studies, but only circumstantial evidence from clinical studies. Keywords: Bacterial translocation; barrier function; lactobacilli; probiotics.

A retrospective analysis of hepatic injury in horses with proximal enteritis (1984-2002).

The purpose of this study was to test the hypothesis that horses with proximal enteritis (PE) are predisposed to hepatic injury. We also determined whether the presence of liver injury in horses with PE was associated with other clinicopathologic abnormalities or affected outcome. The medical records of all horses admitted for evaluation of colic and gastric reflux between 1984 and 2002 were reviewed. Horses were considered to have PE if the diagnosis was made at surgery or postmortem examination or if they had clinical findings consistent with PE. Horses with a small intestinal strangulating obstruction (SISO) were used as the control group. Historic and clinicopathologic data were collected for each horse. The data were analyzed by descriptive statistics, parametric and nonparametric analyses, and logistic regression. Horses with PE had significantly higher serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities than horses with SISO (P < .05). Horses with PE were 12.1 times more likely to have high GGT activities than were horses with SISO. Horses with PE had an increased risk of at least 1 hepatic enzyme being increased if a high anion gap or large volume of reflux was present. Our conclusion is that horses with PE are more likely to have hepatic injury than horses with SISO. The mechanism of hepatic injury may involve ascending infection from the common bile duct, absorption of endotoxin or inflammatory mediators from the portal circulation, or hepatic hypoxia resulting from systemic inflammation and endotoxemic shock.