Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.
Bacterial Infections/physiopathology* ; Bile Acids and Salts/physiology* ; Cholestasis/physiopathology* ; Enteral Nutrition ; Gastrointestinal Microbiome/physiology* ; Humans ; Intestinal Diseases/physiopathology* ; Intestines/physiopathology* ; Liver/physiopathology* ; Liver Diseases/physiopathology* ; Parenteral Nutrition/adverse effects* ; Short Bowel Syndrome/physiopathology* ; Signal Transduction

OBJECTIVE: To investigate the functional pathways enriched and differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of patients with gram-positive and gram-negative sepsis. METHODS: Dataset GSE9960 obtained from NCBI GEO database containing PBMC samples from 16 non-infectious systematic inflammatory response syndrome (SIRS) patients, 17 gram-positive septic patients and 18 gram-negative septic patients were included in the study. Functional pathway annotations were conducted by gene set enrichment analysis and weighted gene co-expression network analysis. DEGs were filtered and master DEGs were then validated in PBMCs of gram-positive septic, gram-negative septic and non-infectious SIRS patients. RESULTS: The enriched gene sets in gram-positive sepsis and gram-negative sepsis were significantly different. The results indicated the opposite co-expression networks in SIRS and gram-negative sepsis, and the entirely different co-expression networks in gram-positive and gram-negative sepsis. Furthermore, we validated that CONCLUSIONS The results indicate that there are differences in the mechanism and pathogenesis of gram-positive and gram-negative sepsis, which may provide potential markers for sepsis diagnosis and empirical antimicrobial therapy.
Biomarkers/analysis* ; Gene Expression Profiling ; Gram-Negative Bacterial Infections/physiopathology* ; Gram-Positive Bacterial Infections/physiopathology* ; Humans ; Leukocytes, Mononuclear/pathology* ; Sepsis/physiopathology*

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western ; Caffeic Acids ; Cell Line, Tumor ; Cell Proliferation ; DNA, Bacterial/analysis/genetics ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/*metabolism ; Gastric Mucosa/*metabolism/pathology ; Gastritis/pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/metabolism/pathology/physiopathology ; Helicobacter pylori/pathogenicity/physiology ; Humans ; NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism ; Peptide Fragments ; Phenylethyl Alcohol/analogs & derivatives ; Proto-Oncogene Proteins c-jun ; Repressor Proteins ; Transcription Factor AP-1/*biosynthesis ; Transcription Factors/*metabolism ; beta Catenin/*metabolism

Infective endocarditis (IE) has been increasingly diagnosed in patients without previously detected predisposing heart disease, but its clinical features have yet to be fully determined. A recent single-center study including echocardiographic images and surgical findings investigated the incidence of undiagnosed, clinically silent valvular or congenital heart diseases and healthcare-associated infective endocarditis (HAIE). The study confirmed that a large proportion of patients with IE have no previous history of heart disease. Analysis of underlying disease in these patients showed that undetected mitral valve prolapse was the most common disease, followed by an apparently structurally normal valve. The patients who developed IE of apparently structurally normal valves had different clinical characteristics and worse outcomes. IE involving a structurally normal valve was associated with both nosocomial and non-nosocomial HAIE, whereas community-acquired IE was more frequent than HAIE. The pathophysiologic mechanism involving the development of non-HAIE or community-acquired IE due to predominantly staphylococcal infection in an apparently structurally normal valve is not yet clearly understood. Structurally normal valves are not necessarily free of regurgitation or abnormal turbulence and, given the dynamic nature and fluctuating hemodynamic effects of conditions such as poorly controlled hypertension, end-stage renal disease, and sleep apnea, further investigation is necessary to evaluate the potential role of these diseases in the development of IE. An apparently normal-looking valve is associated with IE development in patients without previously recognized predisposing heart disease, warranting repartition of at-risk groups to achieve better clinical outcomes.
Adult ; Aged ; Community-Acquired Infections/diagnosis/*epidemiology/microbiology/physiopathology/therapy ; Cross Infection/diagnosis/*epidemiology/microbiology/physiopathology/therapy ; Echocardiography, Doppler, Color ; Endocarditis, Bacterial/diagnosis/*epidemiology/microbiology/physiopathology/therapy ; Female ; Heart Valves/*microbiology/physiopathology/ultrasonography ; Humans ; Incidence ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Risk Factors

OBJECTIVETo study the effects of perinatal recurrent infection on the brain development in immature mice.

METHODSSix pregnant C57BL6 mice were randomly assigned to three groups: intrauterine infection, perinatal recurrent infection and control. The intrauterine infection group was intraperitoneally injected with LPS (0.5 mg/kg) on the 18th day of pregnancy. The perinatal recurrent infection group was injected with LPS (0.5 mg/kg) on the 18th day of pregnancy and their offsprings were intraperitoneally injected with the same dose of LPS daily from postnatal day 3 to 12. The control group was administered with normal saline at the same time points as the recurrent infection group. The short-time neurobehaviors were assessed on postnatal day 13. The mice were then sacrificed to measure brain weights and neuropathological changes using cresyl violet staining. Western blot was used to evaluate the expression of TNF-α, Caspase-3 and myelin basic protein (MBP).

RESULTSThe brain weights of the recurrent infection group were significantly lower than the control and intrauterine infection groups (P<0.05) and the recurrent infection group displayed significant neuropathological changes. Perinatal recurrent infection resulted in increased expression levels of TNF-α and Caspase-3, and decreased expression level of MBP compared with the intrauterine infection and control groups (P<0.01). The neurobehavior test showed that the recurrent infection group used longer time in gait reflex, right reflex and geotaxis reflex compared with the control and intrauterine infection groups on postnatal day 13 (P<0.05).

CONCLUSIONSPerinatal recurrent infection may exacerbate inflammatory response and cell death in the immature brain, which may be one of the important factors for perinatal brain injury.

Animals ; Animals, Newborn ; Bacterial Infections ; physiopathology ; Body Weight ; Brain ; growth & development ; pathology ; Caspase 3 ; analysis ; Female ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; analysis ; Pregnancy ; Recurrence ; Reflex

The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) was associated with subsequent ruptured membranes in women with preterm labor and intact membranes who had a clinically indicated amniocentesis. This retrospective cohort study included 237 consecutive women with preterm labor (20-34.6 weeks) who underwent amniocentesis. The clinical and laboratory parameters evaluated included demographic variables, gestational age, C-reactive protein (CRP) and amniotic fluid (AF) white blood cell, interleukin-6 (IL-6) and culture results. IAI was defined as a positive AF culture and/or an elevated AF IL-6 level (>2.6 ng/mL). The primary outcome was ruptured membranes in the absence of active labor occurring within 48 hours of amniocentesis. Preterm premature rupture of membranes subsequently developed in 10 (4.2%) women within 48 hr of amniocentesis. Multivariate analysis demonstrated that only IAI was independently associated with the ruptured membranes occurring within 48 hr of amniocentesis. In the predictive model based on variables assessed before amniocentesis, only CRP level was retained. IAI is an independent risk factor for subsequent ruptured membranes after clinically indicated amniocentesis in preterm labor. Prior to amniocentesis, measurement of serum CRP level can provide a risk assessment for the subsequent development of ruptured membranes after the procedure.
Adult ; Amniocentesis/*adverse effects ; Amnion/physiopathology ; Amniotic Fluid/cytology/metabolism/microbiology ; Bacterial Infections/*etiology/microbiology ; C-Reactive Protein/analysis ; Cohort Studies ; Demography ; Female ; Gestational Age ; Humans ; Inflammation/*etiology ; Interleukin-6/metabolism ; Leukocytes/cytology ; Multivariate Analysis ; Mycoplasma/isolation & purification ; Obstetric Labor, Premature/*etiology ; Pregnancy ; ROC Curve ; Retrospective Studies ; Risk Factors ; Ureaplasma urealyticum/isolation & purification

OBJECTIVETo investigate the bactericidal effects of Jinghua Weikang Capsule and its major component Chenopodium ambrosioides L. on antibiotic-resistant Helicobacter pylori.

METHODSFour clinical antibiotic-resistant H. pylori strains were isolated and incubated in liquid medium containing Jinghua Weikang Capsule or Chenopodium ambrosioides L. By means of time-kill curve method, the average colony counts and bactericidal rate were calculated at time points of 0, 4, 8 and 24 h after the incubation and the time-kill curves were charted.

RESULTSBoth Jinghua Weikang Capsule and Chenopodium ambrosioides L. at a concentration of 0.64 g/L showed obvious bactericidal effect against antibiotic-resistant H. pylori after 4 h of incubation.

CONCLUSIONJinghua Weikang Capsule and Chenopodium ambrosioides L. are considered to be active against antibiotic-resistant H. pylori in vitro.

Anti-Bacterial Agents ; pharmacology ; Chenopodium ambrosioides ; Drug Resistance, Microbial ; Drugs, Chinese Herbal ; pharmacology ; Helicobacter Infections ; drug therapy ; physiopathology ; Helicobacter pylori ; drug effects ; isolation & purification ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Plant Preparations ; pharmacology ; Sensitivity and Specificity

In order to investigate the incidence, clinical and microbiologic characteristics of Clostridium difficile infection (CDI) in Korea, a prospective observational study was performed. From September 2008 through January 2010, all patients whose stool was tested for toxin assay A&B and/or C. difficile culture were studied for clinical characteristics. Toxin types of the isolates from stool were tested. The mean incidence of CDI per 100,000 patient-days was 71.6 by month (range, 52.5-114.0), and the ratio of CDI to antibiotic-associated diarrhea was 0.23. Among 200 CDI patients, 37.5% (75/200) was severe CDI based on severity score. Clinical outcome of 189 CDI was as followed; 25.9% (49/189) improved without treatment, 84.3% (118/140) achieved clinical cure and attributed mortality was 0.7% (1/140) with the treatment. Recurrence rate was 21.4% (30/140) and cure without recurrence was 66.4% (93/140). The most common type of toxin was toxin A-positive/toxin B-positive strain (77.5%), toxin A-negative/toxin B-positive strains or binary toxin-producing strains comprised 15.4% or 7.1%, respectively. In conclusion, the incidence of CDI in Korea is a little higher than other reports during the non-epidemic setting. We expect that the change of epidemiology and clinical severity in CDI can be evaluated based on these results.
Aged ; Bacterial Proteins/analysis ; Bacterial Toxins/analysis ; Clostridium Infections/*epidemiology/physiopathology ; Clostridium difficile/*isolation & purification/*pathogenicity ; Diarrhea/epidemiology/microbiology ; Enterocolitis, Pseudomembranous/*epidemiology/microbiology/pathology ; Enterotoxins/analysis ; Feces/microbiology ; Female ; Hospitals ; Humans ; Incidence ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Prospective Studies ; Recurrence ; Republic of Korea/epidemiology ; Treatment Outcome ; Vancomycin/therapeutic use

OBJECTIVETo investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats.

METHODSEighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42.

RESULTSObvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41+/-5.36 in the 0.3 mg/kg infection group and 66.41+/-7.61 in the 0.6 mg/kg infection group vs 8.00+/-0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group [117.8+/-8.7 (0.3 mg/kg infection group) and 194.4+/-13.7 (0.6 mg/kg infection group) vs 56.8+/-3.7 (control group); P<0.01]. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62+/-0.09 in the 0.3 mg/kg infection group and 0.37+/-0.09 in the 0.6 mg/kg infection group vs 0.92+/-0.06 in the control group; P<0.05).

CONCLUSIONSIntrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.

Animals ; Apoptosis ; Bacterial Infections ; physiopathology ; Blood-Brain Barrier ; Brain ; growth & development ; pathology ; Female ; Maze Learning ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Wistar ; Uterus ; microbiology

We evaluated the effects of a combined therapy of pre-blockade endogenous nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn piglets were randomized into 5 groups: control, E. coli pneumonia control, pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI. Only two of 8 animals with L-NAMEpretreated pneumonia survived. Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection. This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.
Treatment Outcome ; Swine ; Survival Rate ; Sepsis/diagnosis/drug therapy/physiopathology ; Pulmonary Gas Exchange/*drug effects ; Premedication/*methods ; Pneumonia, Bacterial/diagnosis/*drug therapy/physiopathology ; Oxygen Consumption/*drug effects ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide/*administration & dosage ; NG-Nitroarginine Methyl Ester/*administration & dosage ; Injections, Intravenous ; Escherichia coli Infections/diagnosis/*drug therapy/physiopathology ; Drug Therapy, Combination ; Animals, Newborn ; Animals ; Administration, Inhalation