OBJECTIVETo observe the efficacy of electroacupuncture on sepsis and explore its mechanism.

METHODSFifty cases were randomized into an observation group (26 cases) and a control group (24 cases). The therapeutic programs of anti-infection, anti-shock, respiratory support and nutritional support were provided, but the drugs that might affect gastrointestinal motility were not prescribed in two groups. In the observation group, on the basic treatment as above, electroacupuncture was applied to Zusanli (ST 36), Tianshu (ST 25), Shangjuxu (ST 37), Xiajuxu (ST 39). The excretion ratio of lactulose to mannitol (L/M) in urine and serum D-lactic acid level were detected before and after treatment, as well as the time of target feeding of the patients in two groups. The efficacy was compared between two groups.

RESULTSAfter treatment for 3 days, L/M was (0.083 +/- 0.020) and serum D-lactic acid was (0.155 +/- 0.196) mmol/L in the observation group, which were apparently reduced as compared with (0.123 +/- 0.034) and (0.193 +/- 0.377) mmol/L in the control group respectively (both P < 0.05). The time of target feeding was (93.69 +/- 27.58) h in the observation group, which was shortened apparently than (118.17 +/- 40.28) h in the control group (P < 0.05). The total effective rate was 80.8% (21/26) in the observation group, which was better than 54.2% (13/24) in the control group (P < 0.05).

CONCLUSIONConventional treatment combined with electroacupuncture can improve intestinal permeability in sepsis patients, recover intestinal function as quickly as possible to achieve target feeding.

Acupuncture Points ; Aged ; Aged, 80 and over ; Electroacupuncture ; Female ; Humans ; Intestines ; metabolism ; Lactulose ; metabolism ; Male ; Mannitol ; metabolism ; Middle Aged ; Permeability ; Sepsis ; metabolism ; therapy

OBJECTIVETo investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats.

METHODSBT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary (99m)Tc-diethylenetriamine pentaacetatic acid ((99m)Tc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of (51)Cr in the intestine.

RESULTSBT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose.

CONCLUSIONSOur study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

Animals ; Bacterial Translocation ; drug effects ; Endotoxins ; analysis ; Gastrointestinal Agents ; pharmacology ; Intestines ; metabolism ; microbiology ; Lactulose ; pharmacology ; Liver Cirrhosis, Experimental ; metabolism ; microbiology ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDLeakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.

METHODSHealthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured.

RESULTSIntestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05).

CONCLUSIONRhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.

Animals ; Claudin-5 ; metabolism ; Intestinal Mucosa ; drug effects ; metabolism ; Lactulose ; metabolism ; Male ; Mannitol ; metabolism ; Occludin ; metabolism ; Plant Extracts ; chemistry ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Sepsis ; drug therapy ; metabolism ; Zonula Occludens-1 Protein ; metabolism

PURPOSE: D-lactate, optical isomer of L-lactate is not a human metabolite. Once the D-lactate enters the human body, it is mainly metabolized in liver. The metabolism of D-lactate can be changed in patients with decompensated liver cirrhosis with the exposure of antibiotics and the frequent trial of lactulose, if neccessory. The aim of this study is to analyze blood D-lactate level in cirrhotic patients and it's relationship with the degree of hepatic insufficiency and acid-base imbalance. METHODS: Plasma L-lactate and D-lactate levels were measured in 40 cirrhotic patients classified by Child-Pugh system with L-LDH and D-LDH with comparison of their changes before and after the use of antibiotics and lactulose(n=14). Also, acid-base disorders were analyzed in 35 cirrhotic patients, and plasma L, D-lactate levels were determined in each acid-base disorder. RESULTS: Plasma D-lactate level was not significantly elevated in cirrhotic patients compared to the control group(2.34+/-.48 mmol/L vs. 1.63+/-.26 mmol/ L, p=NS), but some patients(n=4, 10%) revealed abnormally elevated D-lactate level. The plasma L, D- lactate levels were not different in subgroups classified by Child-Pugh system as well as by underlying causes of liver cirrhosis, and plasma D-lactate level was not sugnificnatly different before and after the exposure of antibiotics and lactulose. Plasma D-lactate level was significantly increased in 3 patients with respiratory alkalosis and metabolic acidosis(12+/-.98 mmol/L) compared to others(p<0.05). CONCLUSION: These results suggest that, regardless of its decompensated degree and exposure to drugs, a subset of patients with liver cirrhosis can develop elevation of D-lactate in blood, particularly when metabolic acidosis is accompanied.
Acid-Base Imbalance* ; Acidosis ; Alkalosis, Respiratory ; Anti-Bacterial Agents ; Hepatic Insufficiency ; Human Body ; Humans ; Lactic Acid ; Lactulose ; Liver ; Liver Cirrhosis ; Metabolism ; Plasma*

Animals ; Burns ; drug therapy ; metabolism ; physiopathology ; Interleukin-18 ; genetics ; metabolism ; Lactulose ; therapeutic use ; Lipopolysaccharides ; blood ; Liver ; metabolism ; physiopathology ; Lung ; metabolism ; physiopathology ; Male ; Multiple Organ Failure ; prevention & control ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.
Animals ; Apoptosis/*physiology ; Claudins/*metabolism ; Colitis/chemically induced/immunology/*physiopathology ; Colon/immunology/physiopathology ; Dextran Sulfate ; Intestinal Mucosa/*physiopathology ; Lactulose/metabolism ; Mannitol/metabolism ; Mannose-Binding Lectin/*immunology ; Permeability ; Rats ; Rats, Sprague-Dawley ; Sucrose/analogs & derivatives/metabolism ; Up-Regulation

Whether hydrogen and methane gas produced during lactulose breath test (LBT) are associated with symptoms of irritable bowel syndrome (IBS) is not determined. We aimed to investigate whether hydrogen and methane on LBT are associated with IBS symptoms. Sixty-eight IBS patients meeting the Rome III criteria for IBS, and 55 healthy controls, underwent LBT. The IBS subjects recorded their customary gastrointestinal symptoms on a questionnaire using visual analogue scales. LBT positivity was defined to be above 20 ppm rise of hydrogen or 10 ppm rise of methane within 90 min. Gas amounts produced during LBT were determined by calculating area under the curve of hydrogen and methane excretion. Symptom severity scores were not different between the LBT (+) IBS and LBT (-) IBS subjects and also between methane producers and non-methane producers. Gas amounts produced during LBT were not associated with IBS symptoms, except a weak correlation between total gas amounts and a few IBS symptoms such as bloating (r = 0.324, P = 0.039), flatulence (r = 0.314, P = 0.046) and abdominal pain (r = 0.364, P = 0.018) only in LBT (+) IBS. In conclusion, hydrogen and methane gas on LBT are not useful for predicting the customary symptoms and subtypes of IBS.
Abdominal Pain/etiology ; Adult ; Area Under Curve ; Breath Tests ; Female ; Flatulence/etiology ; Gases/analysis ; Humans ; Hydrogen/*analysis ; Irritable Bowel Syndrome/*diagnosis ; Lactulose/*metabolism ; Male ; Methane/*analysis ; Middle Aged ; ROC Curve ; Risk Factors

OBJECTIVETo explore the intestinal mucosal barrier protective effect of herbal medicine Compound Tongfu Granule (CTG) in patients with liver cirrhosis of decompensation stage.

METHODSFifty patients enrolled were randomly assigned to the control group (26 cases) and the CTG group (24 cases), and 30 healthy adults were set up as normal control. After 2-week treatment, the intestinal permeability (IP, represented by urinary lactulose/mannitol excretion rate), plasma endotoxin (EDT) level, and change of enteric bacteria (EB) in patients were observed before and after treatment, and compared with those in the normal control.

RESULTSBefore treatment, cirrhotic patients showed significantly higher levels of IP, EDT, and intestinal bacilli, but a lower amount of enteric bifidobacteria as compared with those the normal control. After 2-week treatment, levels of EDT and urinary excretion rate of lactulose in the CTG group were lowered more significantly than those in the control group (P < 0.05), while the amount of bifidobacteria in the CTG group increased accompanied with intestinal bacilli significantly lowered to near the levels in the normal control (P < 0.05, P < 0.01).

CONCLUSIONCTG can improve the intestinal barrier function, correct the intestinal bacteria disturbance, and significantly reduce the entero-derived endotoxemia in cirrhotic patients of decompensation stage.

Adult ; Aged ; Aged, 80 and over ; Bifidobacterium ; isolation & purification ; metabolism ; Cell Membrane Permeability ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Endotoxins ; metabolism ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lactulose ; metabolism ; Liver Cirrhosis ; drug therapy ; metabolism ; microbiology ; pathology ; Male ; Middle Aged ; Treatment Outcome

We treated a 49-yr-old man with neostigmine, who had liver cirrhosis, acute hepatic encephalopathy, and acute intestinal pseudoobstruction. He was admitted in a state of hepatic confusion. On physical examination, the abdomen was distended; and bowel sound was absent. Plain abdomen film revealed multiple airfluid levels and distention of bowel loops. Initially, we gave him lactulose enemas every 6 hr for one day without improvement in his mental state. Furthermore, he became to a state of coma. Therefore, we gave him 0.5 mg of neostigmine subcutaneously to improve his peristaltic movement, and 2 L of polyethylene glycol electrolyte solution through a nasogastric tube for 4 hr to reduce the production and absorption of gutderived toxins of nitrogenous compounds. After these treatments, the venous ammonia level decreased to the normal range within 12 hr, and the coma disappeared after 2 days. We suggest that neostigmine may be one of the most effective treatments to initiate peristaltic movement and bowel cleansing in cirrhotic patients with acute hepatic encephalopathy and acute intestinal pseudoobstruction.
Air ; Ammonia/metabolism ; Blood Pressure ; Cholinesterase Inhibitors/*pharmacology ; Electrolytes/pharmacology ; Enema ; Fibrosis/*drug therapy ; Hepatic Encephalopathy/*diagnosis/*drug therapy/radiography ; Humans ; Intestinal Pseudo-Obstruction/*diagnosis/*drug therapy/radiography ; Lactulose/pharmacology ; Liver/metabolism ; Male ; Middle Aged ; Neostigmine/*pharmacology ; Peristalsis ; Polyethylene Glycols/pharmacology ; Time Factors

OBJECTIVETo study the change of intestinal mucosa barrier in chronic severe hepatitis B patients and clinical intervention.

METHOD(1) 30 normal healthy controls and 60 chronic severe hepatitis B patients were enrolled in this study. The change of intestinal permeability was determined by urine lactulose/ mannitol ratio (L/M), and the serum diamine oxidase (DAO) was measured. (2) 60 chronic severe hepatitis B patients were randomly divided into two groups: the control group and the treated group, each group has 30 cases. Patients in the control group received standard treatment for 2 weeks, however, in addition to standard treatment, patients in the treated group also received glutamine 10g tid. Endotoxin (ET), DAO and L/M were compared between the two group.

RESULTS(1) Compared to healthy controls, the level of L/M and DAO was significantly increased in chronic severe hepatitis B patients (t = 2.762, P less than 0.01 or t = 6.326, P less than 0.01). (2) Compared to the control group, ET, DAO and L/M were significantly lower 2 weeks after treatment (F = 11.662, P less than 0.01; F = 12.699, P less than 0.01; F = 19.981, P less than 0.01).

CONCLUSION(1) There is an early intestinal mucosa barrier damage in chronic severe hepatitis B patients. (2) Compared to standard treatment, adding glutamine can reverse intestinal mucosa barrier damage.

Administration, Oral ; Adolescent ; Adult ; Amine Oxidase (Copper-Containing) ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Child ; Endotoxins ; blood ; Female ; Glutamine ; pharmacology ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; metabolism ; physiopathology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; physiopathology ; Intestine, Small ; Lactulose ; urine ; Male ; Mannitol ; urine ; Middle Aged ; Permeability ; Treatment Outcome ; Young Adult