Severe Tissue Lesions Research Articles

Environmentally relevant concentrations of microplastics from agricultural mulch and cadmium negatively impact earthworms by triggering neurotoxicity and disrupting homeostasis

Recent research has highlighted the ecological risk posed by microplastics (MPs) from mulching film and heavy metals to soil organisms. However, most studies overlooked real environmental levels of MPs and heavy metals. To address this gap, pristine and aged polyethylene (PE) mulching film-derived MPs (PMPs, 500 mg/kg; AMPs, 500 mg/kg) were combined with cadmium (Cd, 0.5 mg/kg) to assess the acute toxicity to earthworms and investigate associated molecular mechanisms (oxidative stress, osmoregulation pressure, gut microbiota, and metabolic responses) at environmentally relevant concentrations. Compared to Cd alone and Cd + PMPs treatments (11.15 ± 4.19 items/g), Cd + AMPs treatment resulted in higher MPs bioaccumulation (23.73 ± 13.14 items/g), more severe tissue lesions, and increased cell membrane osmotic pressure in earthworms’ intestines. Cd + AMPs induced neurotoxicity through elevated levels of glutamate and acetylcholinesterase. Earthworm intestines (0.98 ± 0.49 to 3.33 ± 0.37 mg/kg) exhibited significantly higher Cd content than soils (0.19 ± 0.01 to 0.51 ± 0.06 mg/kg) and casts (0.15 ± 0.01 to 0.25 ± 0.05 mg/kg), indicating PE-MPs facilitated Cd transport in earthworms’ bodies. Metabolomic analysis showed Cd + AMPs exposure depleted energy and nucleotide metabolites, disrupted cell homeostasis more profoundly than Cd and Cd + PMPs treatments. Overall, co-exposure to AMPs + Cd induced more severe neurotoxicity and disruption of homeostasis in earthworm than Cd and PMPs + Cd treatments. Our study, using Cd and MPs with environmental relevance, underscores MPs’ role in amplifying Cd accumulation and toxicity in earthworms.

Microplastics - Back to Reality: Impact of Pristine and Aged Microplastics in Soil on Earthworm Eisenia fetida under Environmentally Relevant Conditions.

Recently, studies have highlighted the potential danger for soil organisms posed by film-derived microplastics (MPs). However, the majority of those does not accurately reflect the field conditions and the degree of MP contamination that can be found in actual settings. To fill the gap between laboratory and field scenarios, the polyethylene (PE) plastic film was made into PE-MPs and aged. Toxicity and molecular mechanisms of pristine PE-MPs (PMPs) and aged PE-MPs (AMPs) with the concentration at 500 mg/kg of dry weight were determined after 14 days of exposure by measuring the oxidative stress, osmoregulation pressure, gut microbiota, and metabolic responses in earthworms under environmentally relevant conditions. Our research showed that, when compared to PMPs (13.13 ± 1.99 items/g), AMPs accumulated more (16.19 ± 8.47 items/g), caused more severe tissue lesions, and caused a higher increase of cell membrane osmotic pressure in earthworms' intestines. Furthermore, the proportion of probiotic bacteria Lactobacillus johnsonii in the gut bacterial communities was 24.26%, 23.26%, and 12.96%, while the proportion of pathogenic bacteria of the phylum Verrucomicrobia was 2.28%, 4.79%, and 10.39% in the control and PMP- and AMP-exposed earthworms, indicating that the decrease in number of probiotic bacteria and the increase in number of pathogenic bacteria were more pronounced in the gut of AMP- rather than PMP-exposed earthworms. Metabolomic analysis showed that AMP exposure reduced earthworm energy metabolites. Consequently, the constant need for energy may result in protein catabolism, which raises levels of some amino acids, disturbs normal cell homeostasis, causes changes of cell membrane osmolarity, and destroys the cell structure. Our studies showed that aged MPs, with the same characteristics as those found in the environment, have greater toxicity than pristine MPs. The results of this study broaden our understanding of the toxicological effects of MPs on soil organisms under environmentally relevant conditions.

Experimental co-infection of variant infectious bursal disease virus and fowl adenovirus serotype 4 increases mortality and reduces immune response in chickens

Infectious bursal disease virus (IBDV) and fowl adenovirus serotype 4 (FAdV-4) cause infectious bursal disease (IBD) and hydropericardium-hepatitis syndrome, respectively. Recently, studies have reported co-infections of poultry with IBDV and FAdV-4, which is an important problem in the poultry industry. Here, the variant IBDV strain ZD-2018-1 and FAdV-4 isolate HB1501 were used to assess the pathogenicity of co-infection in 1-day-old specific pathogen-free (SPF) chickens. Compared with chickens infected with only FAdV-4, those coinfected with IBDV and FAdV-4 showed enhanced clinical symptoms, higher mortality, more severe tissue lesions, and higher biochemical index levels. Furthermore, the expression of interleukin (IL)-6, IL-1β, and interferon-γ mRNAs in the IBDV-FAdV-4 coinfected chickens was delayed, and the antibody response levels were significantly lower in those birds compared with the FAdV-4-infected chickens. These results indicate that co-infection with variant IBDV ZD-2018-1 and FAdV-4 HB1501 could significantly promote the pathogenicity of FAdV-4 and reduce the immune response in chickens. This study provides the foundation for further investigation of the interaction mechanism in IBDV and FAdV-4 co-infection.

Evidence of H10N8 influenza virus infection among swine in southern China and its infectivity and transmissibility in swine

ABSTRACT Infection with a novel H10N8 influenza virus in humans was first described in China in December 2013, which raised concerns related to public health. This novel virus was subsequently confirmed to have originated from a live poultry market. However, whether this virus can infect other mammals remains unclear. In the present study, antibody specific for H10N8 influenza virus was detected in swine herds in southern China during serological monitoring for swine influenza virus. The pathogenicity and transmissibility of this H10N8 influenza virus to swine was examined. The results showed that swine are susceptible to infection with human-origin H10N8 influenza virus, which causes viral shedding, severe tissue lesions, and seroconversion, while infection with avian-origin H10N8 influenza virus causes only seroconversion and no viral shedding. Importantly, human-origin H10N8 influenza virus can inefficiently be transmitted between swine and cause seroconversion through direct contact. This study provides a new perspective regarding the ecology of H10N8 influenza virus and highlights the importance of epidemiological monitoring of the H10N8 influenza virus in different animal species, which will be helpful for preventing and controlling future infections by this virus.

Secretory IgA in Mucosa of Pharynx and Larynx Plays an Important Role against Influenza A Virus Infection in Kidney Yang Deficiency Syndrome Model.

Objective Influenza virus poses a major threat to human health and has serious morbidity and mortality which commonly occurs in high-risk populations. Pharynx and larynx of the upper respiratory tract mucosa is the first defense line against influenza virus infection. However, the ability of the pharynx and larynx organ to eliminate the influenza pathogen is still not clear under different host conditions. Methods In this study, a mouse model of kidney yang deficiency syndrome (KYDS) was used to mimic high-risk peoples. Two different methods of influenza A (H1N1) virus infection by nasal dropping or tracheal intubation were applied to these mice, which were divided into four groups: normal intubation (NI) group, normal nasal dropping (ND) group, model intubation (MI) group, and model nasal dropping (MD) group. The normal control (NC) group was used as a negative control. Body weight, rectal temperature, and survival rate were observed every day. Histopathologic changes, visceral index, gene expressions of H1N1, cytokine expressions, secretory IgA (SIgA) antibodies of tracheal lavage fluids in the upper respiratory tract, and bronchoalveolar lavage fluids were analyzed by ELISA. Results The MD group had an earlier serious morbidity and mortality than the others. MI and NI groups became severe only in the 6th to 7th day after infection. The index of the lung increased significantly in NI, MI, and MD groups. Conversely, indices of the thymus and spleen increased significantly in NC and ND groups. H&E staining showed severe tissue lesions in MD, MI, and NI groups. H1N1 gene expressions were higher in the MD group compared with the MI group on the 3rd day; however, the MD group decreased significantly on the 7th day. IL-6 levels increased remarkably, and SIgA expressions decreased significantly in the MD group compared with the NC group. Conclusions SIgA secretions are influenced directly by different conditions of the host in the pharynx and larynx in the upper respiratory tract mucosa. In the KYDS virus disease mode, SIgA expressions could be inhibited severely, which leads to serious morbidity and mortality after influenza A virus infection. The SIgA expressions of the pharynx and larynx would be an important target in high-risk populations against the influenza A virus for vaccine or antiviral drugs research.

Co-infection of Mycoplasma gallisepticum and Escherichia coli Triggers Inflammatory Injury Involving the IL-17 Signaling Pathway.

Mycoplasma gallisepticum and Escherichia coli are well known respiratory disease-inducing pathogens. Previous studies have reported that co-infection by MG and E.coli causes significant economic loss in the poultry industry. In order to assess the respiratory toxicity of co-infection in chicken lung, we established a co-infection model to investigate changes in the inflammatory cytokines, lung tissue structure, and transcriptome profiles of chicken lung. The results showed that co-infection caused a wider range of immune damage and more severe tissue lesions than single-pathogen infection. Differentially expressed gene (DEG) analysis indicated that 3,115/1,498/1,075 genes were significantly expressed among the three infection groups, respectively. Gene ontology and KEGG analysis showed genes enriched in response to immune response, cytokine-cytokine receptor interaction, and inflammation-related signaling pathways. Among these pathways, IL-17 signaling was found to be significantly enriched only in co-infection. The expression of IL-17C, CIKS, TRAF6, NFκB, C/EBPβ, and inflammatory chemokines were significantly up-regulated in response to co-infection. Taken together, we concluded that co-infection increased the expression of inflammatory chemokines in lungs through IL-17 signaling, leading to cilia loss and excessive mucus secretion. These results provide new insights into co-infection and reveal target proteins for drug therapy.

Nile tilapia (Oreochromis niloticus) challenged infection by Francisella noatunensis subsp. orientalis via an intragastric route protocol

Francisella noatunensis subsp. orientalis (Fno) is an emerging bacterial pathogen that causes acute or chronic disease in tilapia (Oreochromis sp). Previous studies have established experimental models of Fno infection via intraperitoneal and immersion route. However, there have been no reports of Fno challenge through the gastrointestinal mucosa. In this study, we aimed to determine the median lethal dose (LD50) of Fno by intragastric infection, evaluating the clinical signs, mortality, anatomopathological findings, and recovery of pathogenic bacteria from infected organs of infected tilapia. A total of 200 tilapias, weighing approximately 20 g each, were equally distributed in 20 aquariums, containing 50 L of water maintained at 23 °C; five different randomized treatments, were applied to them. Tilapias were either inoculated (via an intragastric injection) with 300 μL of saline solution (CON) or bacterial solution containing 3.99 × 106 CFU (INF 106), 3.99 × 105 CFU (INF 105), 3.99 × 104 CFU (INF 104) and 3.99 × 103 CFU (INF 103) of Fno. Tilapias were monitored for up to 15 days postinfection (dpi) and mortality rates recorded to calculate the LD50. At 15 dpi, necropsies and microbiological analyses were performed in the surviving fish from all groups. In addition, histopathological evaluations (spleen, gill, intestine, liver, kidney, and brain) and Fno confirmation assays were performed in CON and INF 105 (mortality closer to LD50) inoculated tilapias. While no mortality was observed in CON, mortality rates ranged from 42.5 to 80.0% in the Fno inoculated groups. Both microbiological and PCR analyses confirmed the presence of Fno in the internal tissues (kidneys and spleen) of the INF 105 group. Fno challenged groups showed macroscopic lesions in several tissues, which were consistent with the pathological features of francisellosis. Additionally, INF 105 group had microscopic lesions suggestive of the disease. This study determined the LD50 of Fno by the intragastric infection methodology, after 15 dpi, at 6.32 × 104 CFU. We report for the first time that Fno inoculated through the intragastric route, can reach the internal organs of tilapia, causing lesions in spleen, liver, and kidneys. This finding is important to test the efficacy of substances targeting the intestinal mucosa, such as prebiotics, probiotics, and organic acids. Moreover, the intragastric challenge for Fno presented here may be useful to improve the comprehension of the physiopathology of the disease.

Pathogenicity and Full Genome Sequencing of the Avian Influenza H9N2 Moroccan Isolate 2016.

In Morocco in early 2016, a low pathogenic avian influenza virus serotype H9N2 caused large economic losses to the poultry industry, with specific clinical symptoms and high mortality rates on infected farms. Subsequent to the H9N2 outbreak, the causal agent was successfully isolated from chicken flocks with high morbidity and mortality rates, propagated on embryonated eggs, and fully sequenced. The phylogenetic analysis suggested that the Moroccan isolate could have derived from the Middle East isolate A/chicken/Dubai/D2506.A/2015. This study was designed to assess the pathogenicity of the Moroccan isolate H9N2 in experimentally infected broiler and specific-pathogen-free (SPF) chickens. At 22 days of age, one broiler and two SPF chicken groups were inoculated by dropping 0.2 ml of the H9N2 isolate (107.5 EID50/ml) in both nostrils and eyes. Clinically inoculated chickens with H9N2 displayed mild lesions, low mortality rates, and an absence of clinical signs. The H9N2 virus was more pathogenic in broiler chickens and produced more severe tissue lesions compared to SPF chickens. The viral shedding was detected up to 6 days postinoculation (pi) in oropharyngeal and cloacal swabs in infected birds with a maximum shedding in the oropharynges of the broiler group. All experimental chickens seroconverted and registered high hemagglutination inhibition titers as early as day 7 pi. The present study indicates that the H9N2 virus isolated from a natural outbreak was of low pathogenicity under experimental conditions. However, under field conditions infection with other pathogens might have aggravated the disease.

Strong inflammatory responses and apoptosis in the oviducts of egg-laying hens caused by genotype VIId Newcastle disease virus.

BackgroundNewcastle disease virus (NDV) can cause serious damage to the reproductive tracts of egg-laying hens and leads to egg production and quality reduction. However, the mechanism of severe pathological damage in the oviducts of egg-laying hens after NDV infection has not been fully elucidated. In this study, the correlation between the primary pathological lesions and viral load in the oviducts of egg-laying hens infected with the velogenic genotype VIId NDV strain was evaluated by pathological observation and virus detection. Subsequently, apoptosis, the expression of immune-related genes and lymphocyte infiltration into the infected oviducts were determined to explore the potential causes of the pathological changes.ResultsA higher viral load and severe tissue lesions and apoptotic bodies were observed in the oviduct of NDV-infected hens compared with the control. Immune-related genes, including TLR3/7/21, MDA5, IL-2/6/1β, IFN-β, CXCLi1/2, and CCR5, were significantly upregulated in the magnum and uterus. IL-2 presented the highest mRNA level change (137-fold) at 5 days post infection (dpi) in the magnum. Infection led to CD3+CD4+ and CD3+CD8α+ lymphocyte infiltration into the magnum of the oviduct. A higher viral load was found to be associated with pathological changes and the elevated expression of proinflammatory cytokines in the NDV-infected hens.ConclusionsOur results indicate that the severe lesions and apoptosis in the oviducts of egg-laying hens caused by genotype VIId NDV strains are associated with the excessive release of inflammatory cytokines, chemokines and lymphocyte infiltration, which contribute to the dysfunction of the oviducts and the decrease of egg production in hens.

A Case Report of IgG4-related Syndrome and Literature Review

Background : IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum. Since IgG4-related disease is a multiorgan lymphoproliferative syndrome, it requires a careful differential diagnosis from other distinct disorders (sarcoidosis, immune rheumatic diseases, hematologic diseases, malignancies). Another distinctive feature is a fairly fast response to steroids, that represents the first-choice therapy. Immunosuppressant drugs (azathioprine, mycophenolate mofetil, methotrexate) might be chosen as glucocorticoid-sparing medications or to maintain steroid-induced remission (figure 1). Methods; We report the case of a 70-year-old man and we performed a brief review of loiterature. Results. Our patient has a clinical history including bronchial asthma, aortic aneurysm, histologically confirmed retroperitoneal fibrosis causing hydroureteronephrosis, prostatitis, interstitial pulmonary fibrosis, sclerosing chronic pancreatitis (histologically documented), previous chronic cholecystitis (histologically confirmed), previous pericarditis, xeroftalmia, polyclonal hypergammaglobulinemia, eosinophilia. His serum IgG4 levels were significantly increased (5560 mg/dl). In regard to the above mentioned elements a systemic disease characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in several tissues, was suspected. Immune-rheumatic diseases and infectious diseases were excluded. Steroid treatment was started achieving a significant swift response. Conclusions: Until now IgG4 related disease has been considered rare in the West and exclusive of Japanese and Korean countries, our case report leads us to reflect on the necessity to take into account this disease in patients with multisystemic involvement.

Comparison of pathological changes and viral antigen distribution in tissues of calves with and without preexisting bovine viral diarrhea virus infection following challenge with bovine herpesvirus-1

To compare pathological changes and viral antigen distribution in tissues of calves with and without preexisting subclinical bovine viral diarrhea virus (BVDV) infection following challenge with bovine herpesvirus-1 (BHV-1). 24 Friesian calves. 12 calves were inoculated intranasally with noncytopathic BVDV-1a; 12 days later, 10 of these calves were challenged intranasally with BHV-1 subtype 1. Two calves were euthanized before and 1, 2, 4, 7, or 14 days after BHV-1 inoculation. Another 10 calves were inoculated intranasally with BHV-1 only and euthanized 1, 2, 4, 7, or 14 days later. Two calves were inoculated intranasally with virus-free tissue culture fluid and euthanized as negative controls. Pathological changes and viral antigen distribution in various tissue samples from calves with and without BVDV infection (all of which had been experimentally inoculated with BHV-1) were compared. Following BHV-1 challenge, calves with preexisting subclinical BVDV infection had earlier development of more severe inflammatory processes and, consequently, more severe tissue lesions (limited to lymphoid tissues and respiratory and digestive tracts) and greater dissemination of BHV-1, compared with calves without preexisting BVDV infection. Moreover, coinfected calves had an intense lymphoid depletion in the Peyer patches of the ileum as well as the persistence of BVDV in target organs and the reappearance of digestive tract changes during disease progression. In calves, preexisting infection with BVDV facilitated the establishment of BHV-1 infection, just as the presence of BHV-1 favors BVDV persistence, thereby synergistically potentiating effects of both viruses and increasing the severity of the resultant clinical signs.

The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom

Most snake accidents in North Brazil are attributed to Bothrops atrox, a snake species of the Viperidae family whose venom simultaneously induces local and systemic effects in the victims. The former are clinically more important than the latter, as they cause severe tissue lesions associated with strong inflammatory responses. Although several studies have shown that inflammatory mediators are produced in response to B. atrox venom (BaV), there is little information concerning the molecular pathways involved in innate immune system signaling. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule responsible for transmitting intracellular signals from most toll-like receptors (TLRs) after they interact with pathogen-associated molecular patterns (PAMPs) or other stimuli such as endogenous damage-associated molecular patterns (DAMPs). The MyD88-dependent pathway leads to activation of transcription factors, which in turn induce synthesis of inflammatory mediators such as eicosanoids, cytokines and chemokines. The aim of this study was to investigate the involvement of MyD88 on the acute inflammatory response induced by BaV. Wild-type (WT) C57BL/6 mice and MyD88 knockout (MyD88−/−) mice were intraperitoneally injected with BaV. Compared to WT mice, MyD88−/− animals showed an impaired inflammatory response to BaV, with lower influx of polymorphonuclear and mononuclear cells to the peritoneal cavity. Furthermore, peritoneal leukocytes from BaV-injected MyD88−/− mice did not induce COX-2 or LTB4 protein expression and released low concentrations of PGE2. These mice also failed to produce Th1 and Th17 cytokines and CCL-2, but IL-10 levels were similar to those of BaV-injected WT mice. Our results indicate that MyD88 signaling is required for activation of the inflammatory response elicited by BaV, raising the possibility of developing new therapeutic targets to treat Bothrops sp. poisoning.

An insertional trap for conditional gene expression in Toxoplasma gondii: Identification of TAF250 as an essential gene

Toxoplasmosis is characterized by fast lytic replication cycles leading to severe tissue lesions. Successful host cell invasion is essential for pathogenesis. The division cycle of Toxoplasma gondii is characterized by an unusual cell cycle progression and a distinct internal budding mechanism. To identify essential genes involved in the lytic cycle we devised an insertional gene trapping strategy using the Tet-transactivator system. In essence, a random, active promoter is displaced with a tetracycline regulatable promoter, which if in an essential gene, will result in a conditionally lethal phenotype upon tetracycline addition. We isolated eight mutants with growth defects, two of which displayed modest invasion defects, one of which had an additional cell cycle defect. The trapped loci were identified using expression microarrays, exploiting the tetracycline dependent expression of the trapped genes. In mutant 3.3H6 we identified TCP-1, a component of the chaperonin protein folding machinery under the control of the Tet promoter. However, this gene was not critical for growth of mutant 3.3H6. Subsequently, we identified a suppressor gene encoding a protein with a hypothetical function by guided cosmid complementation. In mutant 4.3B13, we identified TAF250, an RNA polymerase II complex component, as the trapped, essential gene. Furthermore, by mapping the plasmid insertion boundaries we identified multiple genomic rearrangements, which hint at a potential replication dependent DNA repair mechanism. Furthermore, these rearrangements provide an explanation for inconsistent locus rescue results observed by molecular biological approaches. Taken together, we have added an approach to identify and study essential genes in Toxoplasma.

Sublingual and submandibular blood collection in mice: a comparison of effects on body weight, food consumption and tissue damage

In a large number of animal experiments, blood collection is crucial for achieving the study aim. Requirements on sampling techniques used include their practicability, their effectiveness in terms of obtaining the desired blood volume, sample quality and low impact on animal's wellbeing. Numerous methods for blood collection from mice have been published. For large blood volumes, submandibular and sublingual bleeding was developed as alternatives to the retrobulbar bleeding method, which is considered controversial as it results in severe tissue damage. Only a few studies report the use of submandibular and sublingual techniques in mice. In particular, the degree of tissue damage or influence on animal's wellbeing due to submandibular bleeding in conscious mice has not yet been clearly assessed. This gap in the knowledge base has been filled by our exploratory study that revealed clear differences between both techniques. Defence movements during submandibular blood collection in conscious mice resulted in more complications and revealed insufficient blood sample quality due to the prolonged duration of blood collection. In addition, it is likely that these movements may have caused lesions to be more pronounced. Changes in red blood cell parameters (red blood cell count, haemoglobin and haematocrit), in glucose and in total protein concentrations observed in anaesthetized animals were most likely related to anaesthesia. Sublingually punctured mice gained significantly more body weight than submandibularly punctured mice, likely due to less severe tissue lesions and improved healing processes. Based on these results, we recommend the sublingual blood collection technique to be used in mice. However, if the submandibular bleeding technique is used, it should be performed in anaesthetized mice only.

Chronic Exposure and Decontamination of a Marine Sculpin (Myoxocephalus scorpius) to Polychlorinated Biphenyls Using Selected Body Indices, Blood Values, Histopathology, and Parasites as Bioindicators

This study was conducted to assess the health of a subtidal marine sculpin, Myoxocephalus scorpius, naturally exposed in a shipping terminal where polychlorinated biphenyls (PCBs) had been spilled, as well as that of others sculpins after decontamination in the laboratory for 16 weeks. Reference samples were captured at a pristine site upcurrent from the contaminated terminal. Examination of field samples caught by scuba divers showed external and toxicopathic lesions in several tissues; decreased body condition and organ indices; and decreased hemoglobin and lymphocyte levels. No difference in the diversity of parasites was observed between reference and contaminated samples, but abundance was generally greater in fish from the latter site. Although the total number of species of parasites decreased in both groups of depurated sculpins, the abundance of infections on gill and gall bladder was significantly greater in fish from the polluted site. These results suggest that M. scorpius was affected adversely by PCBs and that its responses are ecologically significant as a bioindicator species in degraded habitats. Moreover, remediation might not mitigate the observed anomalies in fish inhabiting the impacted site.

Quantitative Analysis of Virulent Duck Enteritis Virus Loads in Experimentally Infected Ducklings

To better understand the pathogenesis of duck virus enteritis (DVE), the levels of viral DNA in various tissues of ducklings during acute stage of virulent duck enteritis virus (DEV) infection were investigated by using quantitative real-time polymerase chain reaction. The results show that the viral levels of DEV in systemic organs have a close correlation with the progression of disease. The rapid dissemination and active replication of virulent DEV in multiple systemic organs at the early phase of acute infection accelerate the progression of disease. The levels of viral DNA increase sharply soon after developed clinical signs of disease, and the extent of increase and the magnitude of DEV DNA load in various tissues of ducklings after the exhibition of clinical signs may be a critical determinant of the outcome of DEV infection. The relatively high levels of DEV in bursa and small intestine tissues of dead ducklings most likely reflect the abundance of target epithelial and lymphoid cells in these tissues, which therefore play a key role in the pathogenesis of acute DVE and manifest as severe tissue lesions on the bursa and small intestine.

Parasites of Winter Flounder (Pleuronectes americanus) as an Additional Bioindicator of Stress-Related Exposure to Untreated Pulp and Paper Mill Effluent: A 5-Year Field Study

A study was conducted in a marine inlet to assess the effects of untreated discharges from a pulp and paper mill, a municipality, and industries in western Newfoundland on winter flounder (Pleuronectes americanus), a fish species shown previously to be sensitive to environmental contaminants in sediment. The fish were captured by SCUBA divers about 2 km down-current from the mill discharging effluent containing resin acids, and at three reference sites 2 to 11 km away near the opposite shore, each spring in five consecutive years and the fish were necropsied on site. A total of 360 and 339 flounder were examined near the mill and references sites, respectively. Several bioindicators were used to assess fish health including parasites. More fish exhibiting external and microscopic lesions in several tissues, lower condition factors, elevated hepatosomatic index, and delayed reproductive development were observed in samples taken near the paper mill than at the reference sites. A higher prevalence of an ectoparasite, Cryptocotyle lingua, but a significantly lower mean abundance of three metazoans infecting the digestive tract was noted in fish near the mill than in the reference samples. These results, comprising abnormal fish size distribution, low body condition factor, external and internal lesions, enlarged liver, delayed gonadal development, and changes in parasitism, were stress-related, indicative of impaired health, and associated primarily with untreated discharges from the pulp and paper mill. This integrated and multidisciplinary study also provides further evidence on the use of fish parasites as a valid and an additional bioindicator in programs monitoring environmental contaminants.

Bacillus anthracis Edema Toxin Causes Extensive Tissue Lesions and Rapid Lethality in Mice

Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death in BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, lethal toxin. Observations of gross pathology showed intestinal intralumenal fluid accumulation followed by focal hemorrhaging of the ileum and adrenal glands. Histopathological analyses of timed tissue harvests revealed lesions in several tissues including adrenal glands, lymphoid organs, bone, bone marrow, gastrointestinal mucosa, heart, and kidneys. Concomitant blood chemistry analyses supported the induction of tissue damage. Several cytokines increased after ET administration, including granulocyte colony-stimulating factor, eotaxin, keratinocyte-derived cytokine, MCP-1/JE, interleukin-6, interleukin-10, and interleukin-1beta. Physiological measurements also revealed a concurrent hypotension and bradycardia. These studies detail the extensive pathological lesions caused by ET and suggest that it causes death due to multiorgan failure.

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With Stenotrophomonas maltophilia

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With Stenotrophomonas maltophilia

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With