Effect of Tongxieyaofang decoction on colonic mucosal protein expression profiles in rats with visceral hypersensitivity.

OBJECTIVE: To explore the underlying mechanism of action of Tongxieyaofang decoction in rats with visceral hypersensitivity using proteomics technology. METHODS: Twenty-four female Sprague-Dawley rats were randomly divided into three groups: control group, irritable bowel syndrome (IBS) group and Tongxieyaofang treatment group. An IBS model, characterized as visceral hypersensitivity, was established using the odour of mothballs as conditional stimulation and colorectal distension combined with classic physical restraint as non-conditional stimulation. Rats were intragastrically treated with Tongxieyaofang (2 or 4 mL·kg－1·d－1) for 4 weeks. On the 45th day, the rats were dissected and the colonic mucosal proteins were extracted. Differential protein spots were screened by fluorescent two-dimensional differential gel electrophoresis (2D-DIGE), and identified by matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF-MS). Western blotting experiments were performed to verify the changes observed in 2D-DIGE and MALDI-TOF-MS. RESULTS: It was found that the visceral sensitivity of rats in the Tongxieyaofang treatment group (4 mL/kg) was lower than that in the IBS group (P < 0.01). Sixty-one protein spots were differentially expressed between the IBS group and the Tongxieyaofang treatment group. Of these, 23 spots were upregulated in the Tongxieyaofang treatment group, while 38 spots were downregulated. Three specific proteins were successfully identified from the five protein spots with the most obvious changes. The two upregulated proteins were transgelin (TAGLN) and acetaldehyde dehydrogenase 2 (Aldh2) and the downregulated protein was cytokeratin 8 (CK8). CONCLUSION: Tongxieyaofang can dose-dependently ameliorate visceral hypersensitivity in rats and the mechanism of action may involve the upregulation of TAGLN and Aldh2 and the downregulation of CK8.

Separation, purification, structural analysis and immune-enhancing activity of sulfated polysaccharide isolated from sea cucumber viscera.

A novel sulfated polysaccharide (SCVP-1) was isolated from sea cucumber viscera and purified to elucidate its structure and immune-enhancing ability. SCVP-1 was found to be a homogeneous polysaccharide with a relative molecular weight of 180.8 kDa and composed of total sugars (60.2 ±â€¯2.6%), uronic acid (15.3 ±â€¯1.8%), proteins (6.8 ±â€¯0.8%), and sulfate groups (18.1 ±â€¯0.9%). SCVP-1 consisted of mannose, glucosamine, glucuronic acid, N-acetyl-galactosamine, glucose, galactose and fucose at an approximate molar ratio of 1.00:1.41:0.88:2.14:1.90:1.12:1.24. The fourier transform infrared spectra (FT-IR) and nuclear magnetic resonance (NMR) analyses showed that SCVP-1 was a kind of glycosaminoglycan. And the sulfation patterns of the fucose branches were Fuc2,4S, Fuc3,4S and Fuc0S. The surface morphology of SCVP-1 presented loose and irregular sheet structure formed by aggregation of polysaccharide molecules with spherical structure. Moreover, SCVP-1 promoted the production of nitric oxide (NO) and cytokines (IL-1ß, IL-6 and TNF-α) by RAW264.7 cells as well as the expression of related genes (iNOS, IL-1ß, IL-6 and TNF-α) and also enhanced their phagocytic activity through TLR4-mediated activation of the MAPKs and NF-κB signaling pathways. This study suggests that sea cucumber viscera are good sources of polysaccharides and SCVP-1 might be a novel immunomodulator.

Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques.

Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4+ T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence. Finally, after ART interruption, we demonstrate the rapid and, compared to peripheral LNs, earlier seeding of SIV in spleen and mesenteric LNs, thereby emphasizing the importance of these two anatomical sites for viral replication dynamics. Altogether our results advance understanding of early viral seeding in which visceral lymphoid tissues are crucial in maintaining TEM and TFH VRs.

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

Evaluation of the effectiveness and safety of a genetically modified live vaccine in broilers challenged with Salmonella Heidelberg.

Salmonellosis ranks among the major diseases of commercial poultry, and its presence in poultry flocks is responsible for economic losses and risks related to public health. Vaccines are an important tool within integrated programmes to control salmonellosis. The purpose of this study was to assess cross-protection provided by the Poulvac® ST vaccine in the control of Salmonella Heidelberg in experimentally challenged 3- and 21-day-old birds. Eighty birds were identified and separated into four treatments (T1: vaccinated and challenged at 3 days of age, T2: unvaccinated and challenged at 3 days of age, T3: vaccinated and challenged at 21 days of age, and T4: unvaccinated and challenged at 21 days of age). The inoculum was produced from a Brazilian field strain of SH. At the end of the experiment, caecum and liver/spleen samples were collected for quantitative and qualitative analysis of SH, respectively. Analysis of the liver/spleen showed that Poulvac® ST significantly (P ≤ 0.05) reduced the percentage of SH positivity in the group challenged at 3 days of age, while in the group challenged at 21 days this difference was almost considered significant (P = 0.1818). On the other hand, there was no statistically significant difference in SH count in the caecum (CFU/g) in the group challenged at 3 days, but for the group challenged at 21 days the SH counts were significantly (P ≤ 0.05) lower in the vaccinated group when compared to the positive control.

Transfer of CD11c+ lamina propria mononuclear phagocytes from post-infectious irritable bowel syndrome causes mucosal barrier dysfunction and visceral hypersensitivity in recipient mice.

The role of low-grade inflammation in the development of post­infectious irritable bowel syndrome (PI­IBS) has attracted increasing attention. Abnormal CD11c+ mononuclear phagocytes, such as dendritic cells (DCs), macrophages, and monocytes, are involved in the disruption of immune tolerance in organisms, which can lead to the development of chronic inflammatory diseases. The present study tested the hypothesis that CD11c+ lamina propria mononuclear phagocytes (CD11c+ LPMPs) contribute to increased mucosal permeability and visceral hypersensitivity in a PI­IBS mouse model. CD11c+ LPMPs were isolated and purified via the digestion of intestinal tissues and magnetic­activated cell sorting. We detected increased mucosal permeability, visceral hypersensitivity and intestinal inflammation during both the acute and chronic stages of Trichinella infection. Following the transfer of CD11c+ LPMPs from PI­IBS mice into normal mice, low­grade inflammation was detected, as demonstrated by increased IL­4 expression in the ileum, as well as enhanced mucosal permeability, as indicated by decreased transepithelial electrical resistance and the pre-sence of ultrastructural alterations. More importantly, the mice that underwent adoptive transfer of CD11c+ LPMPs from the PI­IBS mice also exhibited increased abdominal withdrawal reflex scores and a decreased threshold. Our data demonstrated that the CD11c+ LPMPs from this PI­IBS mouse model were not only able to transfer enteric inflammation to the normal mice but also caused abnormal intestinal function, characterized by epithelial barrier disruption and visceral hyperalgesia.

A fast and effective determination of the biodistribution and subcellular localization of fluorescent immunoliposomes in freshly excised animal organs.

BACKGROUND: Preclinical research implementing fluorescence-based approaches is inevitable for drug discovery and technology. For example, a variety of contrast agents developed for biomedical imaging are usually evaluated in cell systems and animal models based on their conjugation to fluorescent dyes. Biodistribution studies of excised organs are often performed by macroscopic imaging, whereas the subcellular localization though vital, is often neglected or further validated by histological procedures. Available systems used to define the subcellular biodistribution of contrast agents such as intravital microscopes or ex vivo histological analysis are expensive and not affordable by the majority of researchers, or encompass tedious and time consuming steps that may modify the contrast agents and falsify the results. Thus, affordable and more reliable approaches to study the biodistribution of contrast agents are required. We developed fluorescent immunoliposomes specific for human fibroblast activation protein and murine endoglin, and used macroscopic fluorescence imaging and confocal microscopy to determine their biodistribution and subcellular localization in freshly excised mice organs at different time points post intravenous injection. RESULTS: Near infrared fluorescence macroscopic imaging revealed key differences in the biodistribution of the respective immunoliposomes at different time points post injection, which correlated to the first-pass effect as well as the binding of the probes to molecular targets within the mice organs. Thus, a higher accumulation and longer retention of the murine endoglin immunoliposomes was seen in the lungs, liver and kidneys than the FAP specific immunoliposomes. Confocal microscopy showed that tissue autofluorescence enables detection of organ morphology and cellular components within freshly excised, non-processed organs, and that fluorescent probes with absorption and emission maxima beyond the tissue autofluorescence range can be easily distinguished. Hence, the endoglin targeting immunoliposomes retained in some organs could be detected in the vascular endothelia cells of the organs. CONCLUSIONS: The underlying work represents a quick, effective and more reliable setup to validate the macroscopic and subcellular biodistribution of contrast agents in freshly excised animal organs. The approach will be highly beneficial to many researchers involved in nanodrug design or in fluorescence-based studies on disease pathogenesis.

Oral probiotic treatment of Lactobacillus rhamnosus Lcr35® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress.

AIMS: This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo® ) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. METHODS AND RESULTS: The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. CONCLUSIONS: This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS.

Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation.

BACKGROUND: Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients. METHODS: Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes. RESULTS: Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections. CONCLUSIONS: Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.

Inflammatory stress induces lipid accumulation in multi-organs of db/db mice.

Dyslipidemia and chronic inflammation play crucial roles in the progression of diabetes. This study aimed to investigate the effects of inflammatory stress on lipid accumulation in multi-organs in diabetes. Eight-week-old male db/db mice were randomly assigned to inflamed group with alternating day subcutaneous injection of 10% casein or control group with daily injection of distilled water. The lipid profile and plasma levels of inflammatory cytokines were determined using a clinical biochemical assay and enzyme-linked immunosorbent assay. The effects of inflammation on lipid accumulation in target organs were evaluated by hematoxylin-eosin staining, Oil Red O staining, Filipin staining, and a quantitative intracellular cholesterol assay. The protein expressions of low-density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage-activating protein (SCAP) in tissues were assessed by immunohistochemical staining and western blotting. Results showed that the serum levels of inflammatory cytokines were significantly elevated in casein-injected mice, suggesting that an inflamed diabetic model was established. Furthermore, the protein expressions of inflammatory cytokines in aortas, livers, kidneys, and intestines were significantly increased in inflamed group compared with control. Whereas the serum levels of lipid moieties in inflamed mice were not different compared with the control, inflammatory stress significantly increased lipid accumulation in aortas, livers, kidneys, and intestines, which coincided with increased protein expressions of LDLr, SREBP-2, and SCAP in these organs of inflamed mice. In conclusion, inflammation induces lipid accumulation in multi-organs of db/db mice from the circulation to peripheral tissues, potentially due to lipid redistribution mediated by the disruption of LDLr feedback regulation.

The Influence of Macronutrients on Splanchnic and Hepatic Lymphocytes in Aging Mice.

There is a strong association between aging, diet, and immunity. The effects of macronutrients and energy intake on splanchnic and hepatic lymphocytes were studied in 15 month old mice. The mice were ad-libitum fed 1 of 25 diets varying in the ratios and amounts of protein, carbohydrate, and fat over their lifetime. Lymphocytes in liver, spleen, Peyers patches, mesenteric lymph nodes, and inguinal lymph nodes were evaluated using flow cytometry. Low protein intake reversed aging changes in splenic CD4 and CD8 T cells, CD4:CD8 T cell ratio, memory/effector CD4 T cells and naïve CD4 T cells. A similar influence of total caloric intake in these ad-libitum fed mice was not apparent. Protein intake also influenced hepatic NK cells and B cells, while protein to carbohydrate ratio influenced hepatic NKT cells. Hepatosteatosis was associated with increased energy and fat intake and changes in hepatic Tregs, effector/memory T, and NK cells. Hepatic NK cells were also associated with body fat, glucose tolerance, and leptin levels while hepatic Tregs were associated with hydrogen peroxide production by hepatic mitochondria. Dietary macronutrients, particularly protein, influence splanchnic lymphocytes in old age, with downstream associations with mitochondrial function, liver pathology, and obesity-related phenotype.

Effect of hydrogen-rich water on acute peritonitis of rat models.

OBJECTIVE: To study the effect of hydrogen-rich water (HRW) on acute peritonitis with three different rat models. METHODS: Acute peritonitis was induced by three methods including intraperitoneal injection of lipopolysaccharide (LPS), rats' feces or cecal ligation and puncture (CLP) operation. For each model, male Sprague Dawley rats were used and distributed into saline control group, HRW control group, saline plus model group, and HRW plus model group. Saline or HRW (3 ml per rat) was orally administered by gavage for 7 days beforehand and 3 days after modeling. The efficacy was tested by detecting concentrations of white blood cells (WBCs), plasma endotoxin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α. The activities of malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) in visceral peritoneum tissues were also evaluated. Meanwhile, histopathology examination of visceral peritoneum was performed using hematoxylin and eosin staining. The expression and location of nuclear factor kappaB (NF-κB) in the visceral peritoneum were detected by immunohistochemistry. RESULTS: Three models showed the same result that hydrogen-rich water had an efficient protective effect on acute peritonitis. HRW could significantly lower the levels of WBCs, plasma endotoxin and cytokines, enhance GSH activity and reduce MPO and MDA activities in the peritoneum tissue when compared with that of groups with only saline treated. Simultaneously, we found that HRW could also decrease the NF-κB expression in the peritoneum tissues. CONCLUSION: Hydrogen-rich water could alleviate the severity of acute peritonitis, and it might perform this function by its anti-inflammation, anti-oxidation and anti-bacterial effects and reducing NF-κB expression in the peritoneum tissues.

Botryomycosis.

Botryomycosis is a chronic, granulomatous, infectious disease caused by several genera of bacteria with the formation of grains. The factors involved in its development are low virulence, an intermediate inoculum, and the immunologic status of the host. The pathogenesis of the disease is not well established, but the Splendore-Hoeppli phenomenon, which explains the formation of grains and the antigen-antibody reaction that characterizes the disease, is involved. Diagnosing botryomycosis includes clinical suspicion and microbiologic studies. Isolation of the causative agent and susceptibility tests are essential to provide appropriate treatment.

[Immune senescence and autoimmunity. Does the immune system really age, or just the organs which supply it?]. / Immunseneszenz und Autoimmunität. Altert das Immunsystem wirklich, oder nur die Organe, die es versorgen?

Degenerative ageing processes are to a great extent responsible for organ-specific morbidity and mortality among our population. The incidence of many autoimmune diseases also increases significantly with age, as is evident with rheumatoid arthritis (RA) for example. From an immunological and pathogenetic perspective, that the changes in the immune system of RA patients is comparable to the physiological ageing process seen in healthy individuals approximately 20 years later is of great interest. Despite the manifold functional changes seen in the immune system of older people, the incidence of infection in very elderly patients with RA is only marginally increased, such that immune suppression in older RA patients should be carried out just as consequently as in younger patients. Age-related changes and diseases in other organ systems should receive particular attention, since such complications can have a negative effect on the course of the autoimmune disease as well as the rate of side effects.

Cysteine fluxes across the portal-drained viscera of enterally fed minipigs: effect of an acute intestinal inflammation.

Cysteine is considered as a conditionally indispensable amino acid. Its dietary supply should thus be increased when endogenous synthesis cannot meet metabolic need, such as during inflammatory diseases. However, studies in animal models suggest a high first-pass extraction of dietary cysteine by the intestine, limiting the interest for an oral supplementation. We investigated here unidirectional fluxes of cysteine across the portal-drained viscera (PDV) of multi-catheterized minipigs, using simultaneous intragastric L-[(15)N] cysteine and intravenous L-[3,3D2] cysteine continuous infusions. We showed that in minipigs fed with an elemental enteral solution, cysteine first-pass extraction by the intestine is about 60% of the dietary supply, and that the PDV does not capture arterial cysteine. Beside dietary cysteine, the PDV release non-dietary cysteine (20% of the total cysteine release), which originates either from tissue metabolism or from reabsorption of endogenous secretion, such as glutathione (GSH) biliary excretion. Experimental ileitis induced by local administration of trinitrobenzene sulfonic acid, increased liver and ileal GSH fractional synthesis rate during the acute phase of inflammation, and increased whole body flux of cysteine. However, cysteine uptake and release by the PDV were not affected by ileitis, suggesting an adaptation of the intestinal sulfur amino acid metabolism in order to cover the additional requirement of cysteine linked to the increased GSH synthesis. We conclude that the small intestine sequesters large amounts of dietary cysteine during absorption, limiting its release into the bloodstream, and that the other tissues of the PDV (colon, stomach, pancreas, spleen) preferentially use circulating methionine or cysteine-containing peptides to cover their cysteine requirement.

Microscopical lesions and antigen distribution in bovine fetal tissues and placentae following experimental infection with bovine herpesvirus-1 during pregnancy.

As part of a larger investigation, gross and histopathological examinations were carried out on six aborted and one non-viable calf born to heifers inoculated with bovine herpesvirus-1 (BHV-1) early in the third trimester of pregnancy. Antibody titres in sera collected from the dams confirmed seroconversion following inoculation. Samples of liver, lung, kidney, brain, heart, spleen, hepatic lymph node and placenta were subjected to histopathological examination. Immunohistochemistry for the detection of BHV-1 antigen was performed on liver and placenta from each calf, and on the full range of tissue from three of the six calves. Six dams aborted between 15 and 50 days post-inoculation (dpi) whilst one produced a live but non-viable calf at 51dpi. Consistent microscopical findings in tissues from the six aborted calves were multifocal coagulative necrosis in the liver and necrotic placentitis. The latter was characterized by villous necrosis, necrosis of vascular endothelium and infiltration of necrotic villi by mixed inflammatory cells. Other findings included multifocal necrosis in kidney, spleen and hepatic lymph node as well as haemorrhage in the lung and kidney. Immunohistochemistry confirmed the presence of BHV-1 antigen in association with these lesions and also revealed focal labelling of the endothelium of small blood vessels and surrounding glial processes in the brains of three calves. Virus isolation confirmed the presence of BHV-1 in the placentae from the six aborted calves and in pooled tissues of three of the fetuses. It is concluded that the pathogenesis of BHV-1 abortion involves infection of vascular endothelial cells in multiple tissues including placenta and brain. Furthermore, histopathological examination in suspected cases of BHV-1 abortion should include placenta as well as fetal viscera, and immunohistochemistry is a valuable tool for confirming a diagnosis of infection with the virus.

Systemic distribution of West Nile virus infection: postmortem immunohistochemical study of six cases.

Rare cases of West Nile virus (WNV)-associated inflammation outside the central nervous system (CNS) have been reported. We evaluated the systemic distribution of WNV in postmortem tissues during encephalitis in six patients using immunohistochemistry. WNV antigens were detected in neurons of CNS (all 6 cases), kidney (4 cases), lungs (2 cases), pancreas (2 cases), thyroid (2 cases), intestine (2 cases), stomach (1 case), esophagus (1 case), bile duct (1 case), skin (1 case), prostate (1 case) and testis (1 case). In systemic organs epithelial cells were infected. In none of the six cases were viral antigens identified in hepatocytes, heart, adrenal gland, nerves, skeletal muscles, bone, vessels and fat. All cases in which viral antigens were identified in systemic organs in addition to CNS were severely immunocompromised transplant recipients. With the exception of testis and brain, most foci of infection were not associated with inflammation. While the absence of inflammation may in part be due to patient immunosuppression or to possible transient nature of any host response, compartmentalization of viral antigen to the luminal region of epithelial cells may sequester WNV from immune recognition. Comparison of our findings with previous reports suggests that patients with WNV encephalitis can have widespread systemic infection.

[The biology of visceral fat]. / Biologie des viszeralen Fetts.

Visceral obesity is an independent risk factor for the development of cardiovascular diseases and type 2 diabetes. This is likely to be due to biological characteristics of visceral tissue, which are different from those of subcutaneous adipose tissue in terms of decreased insulin sensitivity and increased lipolytic activity. In addition, the anatomical site of visceral fat could be one potential reason for the increased cardio-metabolic risk associated with visceral obesity. Visceral adipose tissue drains into the portal vein and therefore the liver is exposed to the undiluted metabolites and adipokines released from visceral fat. There are profound differences between visceral and subcutaneous adipocytes in the metabolism, expression of specific receptors and secretion of a specific adipokine pattern, which could contribute to the adverse consequences of visceral obesity.

Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage.

Although 17beta-estradiol (E2) administration after trauma-hemorrhage (T-H) reduces tissue neutrophil sequestration in male rodents, it remains unknown which of the estrogen receptor (ER) subtypes mediates this effect and whether the same ER subtype is involved in all the tissues. We hypothesized that the salutary effects of E2 on attenuation of neutrophil accumulation following T-H are tissue and receptor subtype-specific. Male Sprague-Dawley rats underwent sham operation or T-H (mean blood pressure, 40 mmHg for 90 min and then resuscitation). E2 (50 microg/kg), ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropiolnitrile (DPN; 5 microg/kg), or vehicle (10% dimethyl sulfoxide) was administered subcutaneously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and intercellular adhesion molecule (ICAM)-1 levels in the liver, intestine, and lung were measured (n = 6 rats/group). ER-alpha and ER-beta mRNA levels in sham-operated rats were also determined. T-H increased MPO activity, CINC-1, CINC-3, and ICAM-1 levels in the liver, intestine, and lung. These parameters were improved significantly in rats receiving E2 after T-H. Administration of the ER-alpha agonist PPT but not the ER-beta agonist DPN improved the measured parameters in the liver. In contrast, DPN but not PPT significantly improved these parameters in the lung. In the intestine, ER subtype specificity was not observed. ER-alpha mRNA expression was highest in the liver, whereas ER-beta mRNA expression was greatest in the lung. Thus, the salutary effects of E2 administration on tissue neutrophil sequestration following T-H are receptor subtype and tissue-specific.