Diverse Etiologic Agents Research Articles

Differential Regulation of the Asthmatic Phenotype by the Aryl Hydrocarbon Receptor.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the metabolism of xenobiotics. There is growing evidence that the AhR is implicated in physiological processes such proliferation, differentiation, and immune responses. Recently, a role of the AhR in regulating allergic asthma has been suggested, but whether the AhR also regulates other type of asthma, particularly occupational/irritant-induced asthma, remains unknown. Using AhR-deficient (Ahr−/−) mice, we compared the function of the AhR in the response to ovalbumin (OVA; allergic asthma) vs. chlorine (Cl2; irritant-induced asthma) exposure. Lung inflammation and airway hyperresponsiveness were assessed 24h after exposure to Cl2 or OVA challenge in Ahr−/− and heterozygous (Ahr+/−) mice. After OVA challenge, absence of AhR was associated with significantly enhanced eosinophilia and lymphocyte influx into the airways of Ahr−/− mice. There were also increased levels of interleukin-4 (IL-4) and IL-5 in the airways. However, OVA-induced airway hyperresponsiveness was not affected. In the irritant-induced asthma model caused by exposure to Cl2, the AhR did not regulate the inflammatory response. However, absence of AhR reduced Cl2-induced airway hyperresponsiveness. Collectively, these results support a differential role for the AhR in regulating asthma outcomes in response to diverse etiological agents.

Cryptospordiosis: An infectious emerging protozoan zoonosis of public health significance

Zoonoses caused by diverse etiological agents, are important from public health and economic point of view, and are reported in humans and animals from developing and developed nations of the world. Cryptosporidiosis is an emerging food and waterborne zoonotic protozoan disease that has been detected in both human and animal populations all over the world. The source of infection is exogenous, and the ingestion of contaminated food and water is the principal mode of transmission. The oocysts of Cryptosporidium are abundant and pervasive in ambient water, where they can survive for months. It prefers epithelial cells found in the digestive tracts of a wide range of hosts. Waterborne transmission through drinking water or a swimming pool is common, resulting in outbreaks in several nations throughout the world. The disease can manifest itself in sporadic or epidemic forms. The infection has been recorded in immunocompetent and immunocompromised individuals. The watery diarrhea, abdominal cramps, nausea, anorexia and low grade fever are most commonly observed symptoms. The laboratory help is required to make an unequivocal diagnosis of disease. The preventive strategies include excellent hygienic measures to avoid the contamination of food and water by oocysts of Cryptosporidium. In addition, the role of veterinarian is highly imperative for the management of disease in domestic animals.

Murine models for studying immunopathogenesis in gastrointestinal lesions: How to go about it

Gastro-intestinal (GI) lesions are common outcome to diverse etiological agents affecting the GI tract. It requires significant expertise to accurately diagnose the fundamental cause and treat accordingly. A better understanding of the immunological underpinning of these lesions is of great importance to ensure their successful management. Availability of specific animal models allows us to understand the subtle differences among diverse disease conditions and help decide upon the treatment trajectories. Since murine models are best suited for studying the immunopathogenesis of any disease, we will restrict our discussions here to the available murine models and their applications to study gastrointestinal lesions. In this review, we have systematically examined and compared the variety of mice models that are routinely used to study Inflammatory Bowel disease (IBD) and also how they can be leveraged to address specific questions relating to IBD.

Assessment of predisposing effect of Chicken Anaemia Virus (CAV) in Gangrenous Dermatitis (GD) outbreaks in commercial layer chicken

Gangrenous dermatitis (GD) is an economically important disease in commercial layer chicken and its severity have increased for the past few years despite effective farm management system and suitable antibiotic treatments. This study was designed to explore the immunosuppressive role of Chicken Anaemia Virus (CAV) in gangrenous dermatitis outbreaks in Namakkal region of Tamil Nadu, India. Thirty commercial white leghorn layer flocks were investigated in and around Namakkal District of Tamil Nadu State, India. Detailed farm history was collected. Serum and blood samples were collected to screen the antibody titer and haemogram, respectively. Heart blood, liver samples from dead birds and cutaneous swabs from ailing and dead carcasses were taken to identify the bacterial etiology. Detailed necropsy was conducted and the gross lesions were recorded. Thymus, bone marrow, liver and muscle were collected for screening of CAV by Polymerase chain reaction and histopathological studies. The sera samples showed 100 per cent positivity for CAV and the blood profile showed anaemic picture. The GD affected birds showed anaemia, severe serosanguinous, haemorrhagic and gangrenous lesions in wings, suncutaneous tissue and interdigital space of toes. Necropsy revealed severe gangrene, extravasation of serosanguinous fluid from the skin, hypoplasia of thymus and paleness of bone marrow. Microscopic examination showed hypoplasia / atrophy of thymus and replacement of erythropoietic tissue of bone marrow with fat cells. Cultural examination exhibited the presence of Closrtidium perfringens, Staphylococcus aureus and E. coli. The significance of the study was that CAV is the major culprit in GD outbreaks in poultry which invites the diverse etiological agents by its immunosuppressive action.

Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases.

Neddylation is a ubiquitin-like posttranslational modification that conjugates neural precursor cell expressed developmentally downregulated-8 (Nedd8) to specific substrates for regulation of protein activity. In light of current researches, the neddylation pathway is aberrant in the pathogenesis of many diseases. In our review, we summarize the versatile roles of neddylation in chronic liver diseases (CLDs). CLDs are one of the leading causes of chronic disease-associated deaths worldwide. There are diverse etiologic agents causing CLDs, mainly including hepatitis B virus (HBV) infection, nonalcoholic fatty liver disease (NAFLD), chronic exposure to alcohol or drugs, and autoimmune causes. So far, however, there remains a paucity of effective therapeutic approach to CLDs. In this review, we summarized the role of the neddylation pathway which runs through the chronic hepatitis B/NAFLD–liver fibrosis–cirrhosis–hepatocellular carcinoma (HCC) axis, a canonical pattern in the process of CLD development and progression. The dysregulation of neddylation may provide a better understanding of CLD pathology and even a novel therapeutic strategy. Correspondingly, inhibiting neddylation via MLN4924, a small molecule compound targeting NEDD8-activating enzyme (NAE), can potently alleviate CLD progression and improve the outcome. On this basis, profiling and characterization of the neddylation pathway can provide new insights into the CLD pathology as well as novel therapeutic strategies, independently of the etiology of CLD.

Rabbit Enteropathies on Commercial Farms in the Iberian Peninsula: Etiological Agents Identified in 2018-2019.

Simple SummaryDigestive disorders are the main cause of economic damage in rabbit farms and, usually, antibiotic treatment is the first choice to control them. Nevertheless, a broad range of infectious agents can be involved in such disorders, as we have observed in our diagnosis work as a veterinary diagnostic laboratory. In this study, a global and updated overview of the frequency of detection of those etiological agents is provided. We have seen differences depending on the age of the affected rabbits, with young rabbits (<15 days old) being the most affected by enteropathogenic Escherichia coli strains, while in preweaning and growing rabbits, a coinfection of two or three pathogens is the most prevalent situation. Clostridium spiroforme and E. coli are the main bacterial agents detected in preweaning rabbits, but enterotoxigenic Bacteroides fragilis has just appeared as a new possible emergent pathogen. Coinfections between bacteria (C. spiroforme and E. coli), parasites (Eimeria spp.), and viruses (rotavirus) are much more frequent than simple infections in growing rabbits; for this reason, complete laboratory studies are required to establish on-farm disease control measures.Digestive disorders are the main cause of economic damage to rabbit farms. This article provides a global and updated overview of the diverse etiological agents causing them, since 757 clinical cases were analyzed during 2018 and 2019—Ninety-five from young rabbits (<15 days old), 117 from preweaning rabbits (15–35 days old), and 545 from growing rabbits. Etiological diagnosis was carried out by bacteriological culture and a set of real time polymerase chain reaction (qPCR) tests for the detection of enteropathogenic Escherichia coli (EPEC), Clostridium spiroforme, C. perfringens, rotavirus A, Bacteroides fragilis, and Eimeria spp. Also, 40 EPEC and 38 non EPEC isolates were investigated for the presence of other colonization factors (afr2, ral, liftA, and paa) by qPCR. EPEC is the most prevalent agent in young rabbits, and although different virulence profiles have been found among EPEC isolates, the liftA+, ral+, and paa+ profile is the most prevalent. C. spiroforme and EPEC are the more frequently detected pathogens in preweaning rabbits, but B. fragilis appears to be a new possible emergent pathogen. In growing rabbits, diverse co-infections between C. spiroforme, Eimeria spp., EPEC, and rotavirus are much more frequent than infections due to only one of them. Other pathogens detected in very few cases are Salmonella spp. and Enterococcus hirae.

Abstract 3694: TonEBP promotes chemoresistance and recurrence of hepatocellular carcinoma via DNA repair of cancer stem cells

Abstract Hepatocellular carcinoma (HCC) is common cancer with a high rate of recurrence and mortality. In addition to diverse etiological agents and wide heterogeneity in individual tumors, inherent resistance to chemotherapeutic agents and a very high rate of recurrence are the major contributing factors to HCC-related death. Cancer stem cells (CSCs) are believed to play a major role in these pathological properties due to its highly efficient DNA damage responses. However, mechanistic understanding of liver CSCs is still lacking, unlike other cancers. Tonicity-responsive enhancer binding protein (TonEBP), also known as NFAT5, is a central component of the pro-inflammatory enhanceosome in which TonEBP bridges activated transcription factors to histone acetyltransferase p300 on gene promoters. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify a function of TonEBP in HCC and liver CSCs. We previously reported that TonEBP promotes hepatocellular carcinogenesis and expression of TonEBP predicts recurrence, metastasis, and death of patients with HCC. Three common sites of TonEBP action in response to diverse etiological agents leading to tumorigenesis and tumor growth were found: cell injury and inflammation, induction by oxidative stress, and stimulation of the COX-2 promoter. The goal of the following study was to understand how TonEBP mediates recurrence and metastasis of HCC. In HCC cells, TonEBP was required for self-renewal and tumorigenic potential of liver CSCs. In addition, TonEBP knockdown reduced the maintenance of liver CSCs. TonEBP mediated DNA repair of the CSCs caused by cisplatin, UV, and mitomycin C - both inter- and intra-strand crosslinks. Chemoresistance by highly activated DNA repair is contributed by TonEBP. We found that TonEBP-mediated DNA repair was carried out by ERCC1/XPF dimer. TonEBP interacted with ERCC1/XPF dimer through rel-homology domain (RHD) and was required for DNA recruitment of the dimer. RHD is required for TonEBP-mediated self-renewal of liver CSCs. TonEBP-ERCC1/XPF complex activated ATM serine/threonine kinase in response to DNA damage leading to activation of NF-κB, STAT3, and expression of pro-inflammatory cytokines, which stimulate the self-renewal of CSCs. Of note, in a cohort of 296 patients with HCC, expression of ERCC1-XPF predicted recurrence, metastasis, and death with high significance in multivariate analyses in TonEBP dependent manner. We conclude that TonEBP-ERCC1/XPF plays a pivotal role in DNA repair-associated chemoresistance and recurrence via liver CSCs. As such, the TonEBP-ERCC1/XPF complex is an attractive target for the prevention of recurrence and effective chemotherapy in HCC. Citation Format: Jun Ho Lee, Jae Hee Suh, Soo Youn Choi, Hyun Je Kang, Orlando D. Schärer, Neung Hwa Park, Hyug Moo Kwon. TonEBP promotes chemoresistance and recurrence of hepatocellular carcinoma via DNA repair of cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3694.

Abstract 1519: TonEBP promotes hepatocellular carcinogenesis, recurrence, and metastasis

Abstract Introduction: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse etiological agents and wide heterogeneity in individual tumors impede effective and personalized treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of pro-inflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Methods: Tumors with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analyzed by qRT-PCR and immunohistochemical analyses of tissue microarrays. Mice with TonEBP haplo-deficiency, and hepatocyte- and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results: TonEBP expression is higher in tumors than in adjacent non-tumor tissues in 92.6% of 296 patients with HCC regardless of etiology associated and DEN-induced mouse HCC. Hepatic induction of TonEBP is mediated by a fall in the miR-223 abundance. The TonEBP expression in tumors and adjacent non-tumor tissues predicts recurrence, metastasis, and death in multivariate analyses. Univariate analysis of two layers of patients showed that higher TonEBP expression was significantly associated with bigger tumor, advanced tumor grade, and vascular invasion. TonEBP promotes HCC initiation and growth via oxidative stress and inflammation in various mouse models of HCC. The association between TonEBP and inflammation was confirmed from analysis of the RNA-seq dataset from TCGA. TonEBP-dependent stimulation of tumor growth was dependent on COX-2. TonEBP drives the expression of COX-2 by stimulating the promoter in association with transcription factor YY1 and histone acetyltransferase p300. TonEBP is required for the recruitment of both YY1 and p300 to the promoter in situ. The interaction between TonEBP and YY1 is mediated by RHD and spacer domain. TonEBP deficiency resulted in reduced COX-2 expression leading to reduced production of prostaglandin E2 in various animal models of HCC and acute liver injury. In addition, self-renewal of hepatic cancer stem cells (hCSCs) contributing to recurrence was driven by TonEBP in association with ERCC1. In mouse models of HCC and acute liver injury, three common sites of TonEBP action in response to diverse etiological agents leading to tumorigenesis and tumor progression were found: cell injury and inflammation, induction by oxidative stress, and stimulation of the COX-2 promoter Conclusions: TonEBP is a key component of the common pathway in tumorigenesis and tumor progression of HCC in response to diverse etiological insults. TonEBP is involved in multiple steps along the pathway rendering it an attractive therapeutic target as well as a prognostic biomarker. Citation Format: Jun Ho Lee, Jae Hee Suh, Soo Youn Choi, Hyun Je Kang, Hwan Hee Lee, Whaseon Lee-Kwon, Jiyoung Park, Kyungjae Myung, Neung Hwa Park, Hyug Moo Kwon. TonEBP promotes hepatocellular carcinogenesis, recurrence, and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1519.

Etiology and antibiotic susceptibility of bacterial pathogens responsible for community-acquired urinary tract infections in Poland.

Urinary tract infections (UTIs) are some of the most common infections in both community and hospital settings infections. With their high rate of incidence, recurrence, complications, diverse etiologic agents, as well as growing antibiotic resistance, UTIs have proven to be a serious challenge for medical professionals. The aim of this study was to obtain data on the susceptibility patterns of pathogens responsible for UTIs in Poland to currently used antibiotics. A total of 396 bacterial isolates were collected between March and May 2013 from 41 centers in all regions of Poland. The majority of isolates were from adult patients (96.2 %); 144 (37.8 %) patients were diagnosed with uncomplicated UTI, while the remaining 237 (62.2 %) had a complicated infection. The most prevalent pathogen was Escherichia coli (71.4 %), followed by Klebsiella spp. (10.8 %) and the Proteae group (7.6 %). Escherichia coli was responsible for 80.6 % of cases of uncomplicated and 65.8 % of complicated infections. Only 65.8 % of E. coli isolates were susceptible to ciprofloxacin (uncomplicated 75.9 %, complicated 58.3 %), 64.0 % to nitrofurantoin (67.2 %, 62.8 %), 65.1 % to trimethoprim/sulfamethoxazole (68.1 %, 62.8 %), and 66.4 % to fosfomycin (77.6 %, 62.2 %). Among E. coli isolates from all UTIs, only 43.4 % were susceptible to ampicillin, with 47.4 % from uncomplicated compared with 40.4 % from complicated infections; 88.2 % to amoxicillin/clavulanic acid (91.4 % vs. 85.9 % complicated); 90.1 % to cefuroxime (93.1 %, 87.8 %); and 94.1 % to cefotaxime (98.2 %, 91.0 %). Thirty-five strains (10.4 %) were capable of producing extended-spectrum β-lactamases (ESBLs). This study demonstrates an increase in multidrug-resistant strains, especially among the leading pathogens associated with UTIs, including E. coli, Klebsiella spp., and Proteus spp.

Exogenous bacterial osteomyelitis in 52 dogs: a retrospective study of etiology and in vitro antimicrobial susceptibility profile (2000–2013)

Background: Most clinical cases of osteomyelitis in dogs involve infectious agents, especially bacteria and fungi. The characterization of these microorganisms may aid in the prevention and treatment of disease.Objective: The aim of this study was to evaluate retrospectively microbiological cultures and in vitro antimicrobial susceptibility profile of isolates from 52 cases of bacterial osteomyelitis in long bones of dogs over 2000–2013. In 78% of the cases injuries were caused by a motor vehicle accident, but there were a few cases of dog bites (17%) and ascending infection due to pododermatitis (5%).Animals and methods: The isolated microorganisms were identified based on conventional phenotypic methods. In vitro disk diffusion test was performed using 30 different antimicrobials.Results: The isolates were obtained from femur (28%), humerus (16%), tibia (31%), and radius/ulna (25%). Among 52 cases, culture was positive in 88% of cases. Thirteen genus of different species of microorganisms were isolated. The most common microorganisms isolated were Staphylococcus spp. and Escherichia coli followed by Streptococcus spp., enteric bacteria, Corynebacterium sp. and anaerobic bacteria. In 42% of cases cultures were mixed. The most effective drugs against isolated bacteria were amoxicillin and clavulanate potassium (79%) followed by ceftriaxone (69%). High-resistance rates were documented against azithromycin (80%), penicillin (59%), and clindamycin (59%).Conclusions: The present study highlights diverse etiologic agents in cases of infectious bacterial osteomyelitis, with predominance of Staphylococcus genus, and reinforces the importance of obtaining cultures and susceptibility profiles given the high rates of antimicrobial resistance.

Flavobacterium columnare / Myxobolus tilapiae Concurrent Infection in the Earthen Pond Reared Nile Tilapia (Oreochromis niloticus) during the Early Summer

Flavobacterium columnare (F. columnare), the dermotropic Gram negative yellow pigmented bacteria was isolated from different sites of skin ulcerations in the Nile tilapia (Oreochromis niloticus) and Nile catfish (Clarias gariepinus) collected from an earthen pond located at an aquaculture station in Sharkiya Province, Lower Egypt during an acute episode of mass kills during the early summer of 2009. An acute infection with F. columnare was behind the emergent event of mass mortalities among both populations. Many of the Nile tilapias exhibited typical signs of hole - in- the head like lesions from which F. columnare together with the myxosporean spore, Myxobolus tilapiae (M. tilapiae) were retrieved. Most of the cohabitating infected Nile catfishes exhibited severe form of saddle back like ulcer. The identities of the retrieved isolates were confirmed using morphological, biochemical and molecular tools. The research lead us to conclude that the two diverse etiological agents (F. columnare and M. tilapiae) under the triggering effect of the abrupt change in the water quality measures (abrupt rise in the water temperature, ammonia, pH, sharp decrease in dissolved oxygen) have synergized together to induce the above mentioned pathology with the consequent reemergence of fish mass mortalities.

The Comparative Impact of Iron, the B-Complex Vitamins, Vitamins C and E, and Selenium on Diarrheal Pathogen Outcomes Relative to the Impact Produced by Vitamin A and Zinc

Micronutrient supplementation offers one of the most cost-effective means of improving the health and survival of children in developing countries. However, the effects of supplementation with single micronutrients on diarrhea are not always consistent, and supplementation with multi-micronutrient supplements can have negative effects. These inconsistencies may result from the failure to consider the diverse etiological agents that cause diarrhea and the unique effects each micronutrient has on the immune response to each of these agents. This review examines the separate effects that supplementation with the B-complex vitamins, vitamin C, vitamin E, selenium, and iron have on diarrheal disease-related outcomes. Supplementation with iron may increase the risk of infection by invasive diarrheal pathogens, while supplementation with the remaining micronutrients may reduce this risk. These differences may be due to distinct regulatory effects each micronutrient has on the pathogen-specific immune response, as well as on the virulence of specific pathogens. The findings of these studies suggest that micronutrient supplementation of children must take into account the pathogens prevalent within communities as reflected by their diarrheal disease burdens. The effectiveness of combining multiple micronutrients into one supplement must also be reconsidered.

Crohn's Disease and Its Mucocutaneous Involvement

Crohn's disease (CD) is a chronic inflammatory disorder primarily affecting the lower gastrointestinal tract but potentially involving the skin, musculoskeletal system, and eyes. The origin remains unknown, although diverse etiologic agents have been proposed. Characteristic pathologic appearances include the formation of "skip" lesions (discrete regions of inflamed bowel separated by uninvolved mucosae), aphthous ulceration, and fistulation; these signs relate to the presence of an underlying granulomatous transmural inflammation. Cutaneous and oral lesions frequently occur in CD. They may be classified as specific manifestations (in particular, perianal fissures, abscesses, sinuses, and fistulae in ano) with a granulomatous noncaseating inflammation on histologic examination, and nonspecific manifestations (eg, erythema nodosum, neutrophilic dermatoses) with a nonspecific histologic pattern. The diagnosis of CD is based on clinical, endoscopic, radiologic, and histopathologic features. Therapy is mainly aimed at the control of the acute disease and prevention of relapse through the use of mesalazine, corticosteroids, immunosuppressive agents and very recently, anti-tumor necrosis factor-alpha antibodies.

Pathology of granulomatous diseases. Epithelioid granulomas, Part II.

Although many of the disease processes classified under group 1, epithelioid granulomas, result from diverse etiologic agents, they share a common microscopic tissue morphology of relatively well‐organized granulomas containing large numbers of epithelioid cells.

Computed Tomography in Spinal Dysraphism

The value of spinal computed tomography in the diagnosis and management of spinal dysraphism is described. Eight patients with diverse etiological agents were evaluated by clinical examination and subsequent computed tomography, without contrast enhancement. The diagnosis and location of the pathology thus ascertained allowed for appropriate surgery without invasive diagnostic studies. The value of this approach in children and in those patients in whom a low conus medullaris is suspected is obvious.

Orchitis, parotitis and meningoencephalitis due to lymphocytic-choriomeningitis virus.

SINCE Wallgren's1 original description of aseptic meningitis a large number of diverse etiologic agents have been associated with this syndrome. When the meningitis has been accompanied by parotitis and orchitis the likeliest cause has been mumps, whether or not viral diagnostic studies have been performed. With the wider use of laboratory methods, however, Coxsackie and ECHO viruses have been associated with cases showing either orchitis2 , 3 or parotitis4 , 5 although in none of these reports were all three manifestations seen in a single patient. The purpose of this communication is to report this clinical triad in a patient infected with the lymphocytic-choriomeningitis . . .