Liver Abscess With High 18F-FDG Uptake and No 18F-Fluorothymidine Uptake.

ABSTRACT: 18F-FDG accumulates not only in malignant lesions but also in infectious and inflammatory ones. 3'-deoxy-3'-18F-fluorothymidine (FLT) has been investigated as a promising PET tracer for evaluating tumor proliferating activity. We report a case of liver abscess during therapy of pancreatic cancer that underwent FDG PET/CT and FLT PET/CT studies. Although FDG PET/CT demonstrated several regions of increased uptake in the liver, FLT PET/CT showed no increased uptake in the liver.

The Antidepressant Mirtazapine Activates Hepatic Macrophages, Facilitating Pathogen Clearance While Limiting Tissue Damage in Mice.

Background and Aims: Mirtazapine is an atypical antidepressant with antagonist activity for serotonin and histamine receptors. Clinical and experimental evidence suggests that, in addition to treating depression, mirtazapine also alters liver innate immunity and suppresses immune-driven hepatic macrophage activation. Liver macrophages, Kupffer cells, represent the largest collection of fixed macrophages in the body and are critical in regulating hepatic immunity. In addition to their capacity to regulate inflammation, Kupffer cells are key sentinels for clearing blood-borne pathogens, preventing their dissemination within the body. This process involves pathogen capture, phagocytosis, and activation-induced killing via reactive oxygen species (ROS) production. Therefore, we speculated that mirtazapine might adversely alter Kupffer cell pathogen-associated activation and killing. Methods: Mice were treated with mirtazapine and time-dependent changes in Kupffer cells were characterized using intravital microscopy. Macrophage and neutrophil responses, bacterial dissemination, and liver damage were assessed following i.v. infection with a pathogenic strain of S. aureus. Results: Mirtazapine rapidly (within 1.5 h) activates Kupffer cells, indicated by a loss of elongated shape with cellular rounding. However, this shape change did not result in impaired pathogen capture function, and, in fact, generated enhanced ROS production in response to S. aureus-induced sepsis. Neutrophil dynamics were altered with reduced cellular recruitment to the liver following infection. Bacterial dissemination post-intravenous administration was not altered by mirtazapine treatment; however, hepatic abscess formation was significantly reduced. Conclusions: Mirtazapine rapidly activates Kupffer cells, associated with preserved bacterial capture functions and enhanced ROS generation capacity. Moreover, these changes in Kupffer cells were linked to a beneficial reduction in hepatic abscess size. In contrast to our initial speculation, mirtazapine may have beneficial effects in sepsis and warrants further exploration.

Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess.

BACKGROUND: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. RESULTS: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 µM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P < 0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P < 0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P < 0.05). CONCLUSIONS: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

Metabolic Characterization of Peripheral Host Responses to Drainage-Resistant Klebsiella pneumoniae Liver Abscesses by Serum 1H-NMR Spectroscopy.

Purpose: To explore the metabolic characterization of host responses to drainage-resistant Klebsiella pneumoniae liver abscesses (DRKPLAs) with serum 1H-nuclear magnetic resonance (NMR) spectroscopy. Materials and Methods: The hospital records of all patients with a diagnosis of a liver abscess between June 2015 and December 2016 were retrieved from an electronic hospital database. Eighty-six patients with Klebsiella pneumoniae (K. pneumoniae) liver abscesses who underwent percutaneous drainage were identified. Twenty patients with confirmed DRKPLAs were studied. Moreover, we identified 20 consecutive patients with drainage-sensitive Klebsiella pneumoniae liver abscesses (DSKPLAs) as controls. Serum samples from the two groups were analyzed with 1H NMR spectroscopy. Partial least squares discriminant analysis (PLS-DA) was used to perform 1H NMR metabolic profiling. Metabolites were identified using the Human Metabolome Database, and pathway analysis was performed with MetaboAnalyst 3.0. Results: The PLS-DA test was able to discriminate between the two groups. Five key metabolites that contributed to their discrimination were identified. Glucose, lactate, and 3-hydroxybutyrate were found to be upregulated in DRKPLAs, whereas glutamine and alanine were downregulated compared with the DSKPLAs. Pathway analysis indicated that amino acid metabolisms were significantly different between the DRKPLAs and the DSKPLAs. The D-glutamine and D-glutamate metabolisms exhibited the greatest influences. Conclusions: The five key metabolites identified in our study may be potential targets for guiding novel therapeutics of DRKPLAs and are worthy of additional investigation.

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children.

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.

Activation of Toll-like receptors by Burkholderia pseudomallei.

BACKGROUND: Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei. Overall mortality approaches 40% yet little is known about mechanisms of host defense. Toll-like receptors (TLRs) are host transmembrane receptors that recognize conserved pathogen molecular patterns and induce an inflammatory response. The lipopolysaccharide (LPS) of Gram-negative bacteria is a potent inducer of the host innate immune system. TLR4, in association with MD-2, is the archetype receptor for LPS although B. pseudomallei LPS has been previously identified as a TLR2 agonist. We examined TLR signaling induced by B. pseudomallei, B. pseudomallei LPS, and B. pseudomallei lipid A using gain-of-function transfection assays of NF-kappaB activation and studies of TLR-deficient macrophages. RESULTS: In HEK293 cells transfected with murine or human TLRs, CD14, and MD-2, heat-killed B. pseudomallei activated TLR2 (in combination with TLR1 or TLR6) and TLR4. B. pseudomallei LPS and lipid A activated TLR4 and this TLR4-mediated signaling required MD-2. In TLR2-/- macrophages, stimulation with heat-killed B. pseudomallei augmented TNF-alpha and MIP-2 production whereas in TLR4-/- cells, TNF-alpha, MIP-2, and IL-10 production was reduced. Cytokine production by macrophages stimulated with B. pseudomallei LPS or lipid A was entirely dependent on TLR4 but was increased in the absence of TLR2. TLR adaptor molecule MyD88 strongly regulated TNF-alpha production in response to heat-killed B. pseudomallei. CONCLUSION: B. pseudomallei activates TLR2 and TLR4. In the presence of MD-2, B. pseudomallei LPS and lipid A are TLR4 ligands. Although the macrophage cytokine response to B. pseudomallei LPS or lipid A is completely dependent on TLR4, in TLR2-/- macrophages stimulated with B. pseudomallei, B. pseudomallei LPS or lipid A, cytokine production is augmented. Other MyD88-dependent signaling pathways may also be important in the host response to B. pseudomallei infection. These findings provide new insights into critical mechanisms of host defense in melioidosis.

ASAS Centennial Paper: contributions in the Journal of Animal Science to understanding cattle metabolic and digestive disorders.

Acute and subacute ruminal acidosis, bloat, liver abscesses, and polioencephalomalacia (PEM) were reviewed with respect to contributions published in the Journal of Animal Science (JAS) regarding these metabolic and digestive disorders in beef cattle. Increased grain feeding and expansion of the feedlot industry in the 1960s led to considerable research on acidosis, and early publications defined ruminal changes with acute acidosis. The concept of subacute acidosis was developed in the 1970s. Significant research was published during the 1980s and 1990s on adaptation to high-grain diets, effects of ionophores, and the development of model systems to study ruminal and metabolic changes in acidosis. Since 2000, JAS publications on acidosis have largely focused on individual animal variability in response to acid loads and the role of management strategies in controlling acidosis. Increased grain feeding also was associated with an increase in the incidence of liver abscesses, which were quickly linked to insults to the ruminal epithelium associated with acidosis. The role of antibiotics, particularly tylosin, in decreasing the incidence and severity of liver abscesses was a significant contribution of JAS publications during the 1970s and 1980s. Papers on bloat were among the earliest published in JAS related to metabolic and digestive disorders in cattle. Noteworthy accomplishments in bloat research chronicled in JAS include the nature of ruminal contents in legume and feedlot bloat, the role of plant fractions and microbial populations in the development of bloat, and the efficacy of poloxalene, ionophores, and, more recently, condensed tannins in decreasing the incidence and severity of bloat. Although less research has been published on PEM in JAS, early publications highlighting the association between PEM and ruminal acidity and the role of thiaminase in certain forms of the disorder, as well as more recent publications related to the role of sulfur in the development of PEM, are noteworthy contributions. Since the 1940s, outstanding and often-cited review articles have made JAS a highly visible source of information on these disorders. Thus, JAS has played a significant role as a repository for information pertaining to metabolic and digestive disorders in cattle and other ruminants, and it will no doubt continue to be a premier resource for information on these conditions during the second century of the American Society of Animal Science.

Metal chelation and inhibition of bacterial growth in tissue abscesses.

Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn2+ and Zn2+: an activity that results in reprogramming of the bacterial transcriptome. The abscesses of mice lacking calprotectin were enriched in metal, and staphylococcal proliferation was enhanced in these metal-rich abscesses. These results demonstrate that calprotectin is a critical factor in the innate immune response to infection and define metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue.

Inmunoglobulina G en paciente con absceso hepático amebiano / Inmunoglobulin- IgG antibodies- in one patients with amebic liver abscess

La infección por Entamoeba histo­lytica puede causar disentería y absceso hepático amebiano, enfermedades de alta morbi-mortalidad. Se presenta el seguimiento, durante 32 meses, mediante IgG de un paciente de 69 años, proveniente del Chocó en Colombia, con diagnóstico de absceso hepático amebiano, comprobado mediante ecografía, ELISA para IgG, e inmunodifusión y por la respuesta al tratamiento con metronidazol. Las pruebas inmunodiagnósticas han permanecido positivas durante el seguimiento

Clinical significance and mechanism of gas formation of pyogenic liver abscess due to Klebsiella pneumoniae.

We enrolled 22 patients with gas-forming pyogenic liver abscess in a study to assess the mechanism of gas formation. Klebsiella pneumoniae was cultured from specimens from all patients. Gas and pus samples from abscesses revealed four major components: nitrogen, oxygen, carbon dioxide, and hydrogen; this implicates mixed acid fermentation of glucose as the mechanism of gas formation.

Isolation of a chromosomal region of Klebsiella pneumoniae associated with allantoin metabolism and liver infection.

Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. To identify genes associated with liver infection, we used a DNA microarray to compare the transcriptional profiles of three strains causing liver abscess and three strains not associated with liver infection. There were 13 clones that showed higher RNA expression levels in the three liver infection strains, and 3 of these 13 clones contained a region that was absent in MGH 78578. Sequencing of the clones revealed the replacement of 149 bp of MGH 78578 with a 21,745-bp fragment in a liver infection strain, NTUH-K2044. This 21,745-bp fragment contained 19 open reading frames, 14 of which were proven to be associated with allantoin metabolism. The K2044 (DeltaallS) mutant showed a significant decrease of virulence in intragastric inoculation of BALB/c mice, and the prevalence of this chromosomal region was significantly higher in strains associated with liver abscess than in those that were not (19 or 32 versus 2 of 94; P = 0.0001 [chi(2) test]). Therefore, the 22-kb region may play a role in K. pneumoniae liver infection and serve as a marker for rapid identification.

The role of Kupffer cells and regulation of neutrophil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice.

Depletion of mouse Kupffer cells and splenic macrophages following intravenous administration of liposome-entrapped clodronate severely reduced host resistance to primary infection with Listeria monocytogenes. Infection of clodronate-treated mice with a sublethal dose of L. monocytogenes resulted in death of the mice within 3 days. The macrophage depletion resulted in marked increases in bacterial growth in the liver and spleen, but not in other tissues. The proliferation of L. monocytogenes was observed in a large number of hepatocytes that underwent apoptosis. Infiltration of neutrophils in the liver and rapid formation of microabscesses were observed in the control mice after L. monocytogenes infection. However, there was less accumulation of neutrophils in the liver of Kupffer cell-depleted mice than in the control mice. Expression of macrophage inflammatory protein-2 (MIP-2) was enhanced in the livers of both the control and Kupffer cell-depleted mice after L. monocytogenes infection. MIP-2 was also induced in a murine hepatocyte cell line following L. monocytogenes infection. The administration of neutralizing anti-interleukin-8 receptor homolog antibody severely abrogated neutrophil infiltration into the Listeria-infected mouse liver. Anti-MIP-2 antibody moderately reduced neutrophil infiltration and microabscess formation in the liver. These findings indicate that Kupffer cells protect hepatocytes from L. monocytogenes infection and the resultant apoptosis. Moreover, MIP-2 and its related molecules produced by the infected hepatocytes regulate neutrophil infiltration and microabscess formation in primary listeriosis.

Immunohistochemical localization of alpha 1-acid glycoprotein in liver tissues of bovine fetuses, newborn calves, and sick or healthy adult cattle.

OBJECTIVE: To detect localization of alpha 1-acid glycoprotein (alpha 1-AG) antigens in the liver tissue of cattle by use of immunoperoxidase technique. SAMPLE POPULATION: Liver specimens from 6 bovine fetuses, 2 healthy bovine neonates, 2 healthy adult cattle, 3 cattle with experimentally induced hepatic abscesses, and 2 cattle with enzootic bovine leukosis (EBL). PROCEDURE: 3 cattle (with hepatic abscesses) were inoculated with a suspension of Fusobacterium necrophorum in the ruminal vein. Serum alpha 1-AG concentration was determined by use of the single radial immunodiffusion method. Livers from fetuses, newborn calves, and adult or sick cattle were fixed in buffered 10% formalin, dehydrated in alcohol, embedded in paraffin, sectioned, and stained by use of the avidinbiotin complex/immunoperoxidase technique. RESULTS: Sites of localization of the alpha 1-AG antigen positive reaction (AGPR) in the liver obtained from bovine fetuses, neonates, or sick cattle were different. In fetal and newborn calves, the AGPR was detected in the cytoplasm of hepatocytes. Intensity of the reaction varied in direct proportion to alpha 1-AG serum concentration. In adult cattle, the AGPR was particularly intense in hepatocytes adjacent to abscesses or EBL-induced tumors. CONCLUSIONS: The pattern of distribution of cells with AGPR in the liver varied, depending on severity of inflammation. In the cattle with EBL, whether the AGPR was attributable to inflammation could not be clarified, although suppression of immunologic response to tumors may have been a cause of the observed reaction. This association suggests that the glycoprotein may be synthesized, mainly in hepatocytes.

Characterization for virulence of an axenic strain of Entamoeba histolytica: evidence for overexpression of two proteins.

The pattern of protein from membrane and crude homogenate of Entamoeba histolytica strain 462 axenically cultivated (462ac) and submitted to hamster liver passage (462hp) was obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The substrains 462ac and 462hp were compared by zymodeme analysis, erythrophagocytosis, cytopathic effect upon mammalian cells and the capability to induce abscess in hamster liver. The results showed no differences for erythrophagocytosis, cytopathic effect or zymodene for substrains 462ac and 462hp. A type II pathogenic zymodene was observed. Substrain 462ac did not induce liver abscess, but 462hp induced abscesses in 70% of the inoculated animals. The pattern of proteins from plasma membrane and crude homogenate were different. One protein of approximately 45kDa and another of 23 kDa showed at no detectable levels in the membrane of 462ac. A third component of approximately 90 kDa showed more intensively expressed in the 462ac.

A case of gas-containing liver abscess associated with emphysematous change in the gallbladder.

We describe a 77-year-old man with diabetes mellitus who developed a large gas-containing pyogenic liver abscess after admission. Mild elevation of serum biliary enzyme levels suggested probable biliary trouble on admission. Ultrasonography and computed tomography showed a large abscess of the liver with gas formation and the presence of gas within the lumina of the gallbladder and biliary tract when the patient had fever, leukocytosis and evidence of hepato-renal dysfunction. These findings suggest that the large liver abscess may have developed as a result of emphysematous cholecystitis.

[Evaluation of the cases of benign disease with high accumulation on the examination of 18F-fluorodeoxyglucose PET].

In this study 39 cases of abdominal benign disease were examined by PET using 18F-fluorodeoxyglucose (FDG), and 11 cases of them (i.e. 4 cases of liver abscess, 1 of pelvic abscess, 1 of omental abscess, 2 of chronic pancreatitis, 1 of inflammatory pseudotumor of liver, 1 of retroperitoneal leiomyoma and 1 of solid and cystic tumor of pancreas) which showed as high accumulation of FDG as malignant lesion were investigated of their clinical and pathological feature. We used Ci/Cp ratio as index to express the accumulation of FDG in the lesion, which was calculated from radioactivities of the lesion (Ci) and the plasma (Cp) at 60 mins after injection of FDG. The Ci/Cp ratio of the 11 cases was 3.64 +/- 0.77. The pathological feature of the 9 inflammatory cases was high accumulation of inflammatory cells and that of the 2 benign tumor cases was solid proliferation of tumor cells. The serum of the 9 inflammatory cases showed high CRP value. It was considered that the high accumulation of FDG in inflammatory lesions was due to piles of FDG uptake of the many inflammatory cells, while the 2 benign tumors of high accumulation were considered that the tumor cell had as high glucose metabolism as malignancies.

Severity of liver abscesses and efficiency of feed utilization of feedlot cattle.

Relationships of gain, intake, feed efficiency and severity of liver abscesses were evaluated in 12 experiments involving 566 head of individually fed cattle. Concentrate level in the diets ranged from 64 to 95%. In all experiments, livers were scored as unabscessed (0), one or two small abscesses (A-), two to four small active abscesses (A) or one or more large, active abscesses (A+). Based on homogeneity of variances, nine of the experiments were divided into two groups. In one group (four experiments) the incidence of liver abscesses was 32.1% and no significant (P greater than .25) effects of liver abscess severity score on feedlot performance variables were found. In the second group (five experiments), the incidence of liver abscesses was 77.7%. In the second group, liver abscess severity score affected final live weight (P less than .10), hot carcass weight (P less than .0001), dry matter intake (P less than .10), daily gain based on live weight recorded 24 h prior to slaughter (P less than .10), daily gain based on live weight estimated from hot carcass weight with a 62% dressing percentage (P less than .0001), feed efficiency using final live weight estimated from hot carcass weight (P less than .0001) and dressing percentage (P less than .01). In all cases, performance means for cattle with A+ liver scores were the only ones that differed significantly from those of non-abscessed cattle.

Regulation of glucose metabolism by altered pyruvate dehydrogenase activity. I. Potential site of insulin resistance in sepsis.

Regulation of the pyruvate dehydrogenase (PDH) complex has been demonstrated to be a key mechanism in the control of carbohydrate oxidation and conservation of glucose carbon. The effect of sterile inflammation and chronic sepsis (small and large abscess) on the activity of the PDH complex was examined in liver and skeletal muscle. Sepsis altered the proportion of PDH in the active, dephosphorylated form. In hepatic tissue, sterile inflammation leads to a 2.5-fold increase in the proportion of active PDH complex compared to fed control. The same increase in the proportion of active PDH complex was observed in rats with a small septic abscess. However, when the severity of septic episode was increased, the proportion of active PDH complex decreased relative to sterile inflammation or small septic abscess animals. A different pattern in the response to sterile inflammation and sepsis on the proportion of active PDH complex was observed in skeletal muscle compared to liver. In contrast to liver, sterile inflammation did not alter the proportion of active PDH in skeletal muscle. In addition, sepsis (either small or large septic abscess) resulted in a 3-fold decrease in the proportion of active PDH relative to fed control or sterile inflammatory animals. The decrease in the proportion of active PDH complex in sepsis was associated with a corresponding increase in the skeletal muscle acetyl-CoA/CoA ratio. The mechanism responsible for lowered PDH complex activity may have been due to increased PDH kinase activity, secondary to increased skeletal muscle acetyl-CoA/CoA ratios.