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Sample records for infection model mimicking

  1. Model molecules mimicking asphaltenes.

    PubMed

    Sjöblom, Johan; Simon, Sébastien; Xu, Zhenghe

    2015-04-01

    Asphalthenes are typically defined as the fraction of petroleum insoluble in n-alkanes (typically heptane, but also hexane or pentane) but soluble in toluene. This fraction causes problems of emulsion formation and deposition/precipitation during crude oil production, processing and transport. From the definition it follows that asphaltenes are not a homogeneous fraction but is composed of molecules polydisperse in molecular weight, structure and functionalities. Their complexity makes the understanding of their properties difficult. Proper model molecules with well-defined structures which can resemble the properties of real asphaltenes can help to improve this understanding. Over the last ten years different research groups have proposed different asphaltene model molecules and studied them to determine how well they can mimic the properties of asphaltenes and determine the mechanisms behind the properties of asphaltenes. This article reviews the properties of the different classes of model compounds proposed and present their properties by comparison with fractionated asphaltenes. After presenting the interest of developing model asphaltenes, the composition and properties of asphaltenes are presented, followed by the presentation of approaches and accomplishments of different schools working on asphaltene model compounds. The presentation of bulk and interfacial properties of perylene-based model asphaltene compounds developed by Sjöblom et al. is the subject of the next part. Finally the emulsion-stabilization properties of fractionated asphaltenes and model asphaltene compounds is presented and discussed. PMID:25638443

  2. SYSTEMIC INFECTIONS MIMICKING THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Booth, Kristina K.; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

    2012-01-01

    The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989–2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had <10% activity; three patients had a demonstrable ADAMTS13 inhibitor. Compared to 62 patients with severe ADAMTS13 deficiency (<10%) who had no recognized alternative disorders, patients with systemic infections had more frequent fever, coma, renal failure, and the complete “pentad” of clinical features. Seventeen different infectious etiologies were documented. A systematic literature review identified 67 additional patients with a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients, infections with 41 different bacteria, viruses, and fungi were documented, suggesting that many different systemic infections may mimic the presenting clinical features of TTP. Initial plasma exchange treatment is appropriate in critically ill patients with diagnostic features of TTP, even if a systemic infection is suspected. Continuing evaluation to document a systemic infection is essential to determine the appropriateness of continued plasma exchange. PMID:21850657

  3. Blastocystis sp. Infection Mimicking Clostridium Difficile Colitis

    PubMed Central

    Gil, Gaby S.; Chaudhari, Shobhana; Shady, Ahmed; Caballes, Ana; Hong, Joe

    2016-01-01

    We report an unusual case of severe diarrhea related to Blastocystis sp. infection in a patient with end stage renal disease on hemodialysis. The patient was admitted due to profuse diarrhea associated with fever and leukocytosis. Pertinent stool work-up such as leukocytes in stool, stool culture, clostridium difficile toxin B PCR, and serology for hepatitis A, hepatitis B, and hepatitis C and cytomegalovirus screening were all negative. Ova and parasite stool examination revealed Blastocystis sp. The patient was given intravenous metronidazole with clinical improvement by day three and total resolution of symptoms by day ten. PMID:27247810

  4. Infections and skin diseases mimicking diaper dermatitis.

    PubMed

    Van Gysel, Dirk

    2016-07-01

    Diaper dermatitis is a common condition that often prompts parents to seek medical attention. Irritant diaper dermatitis is by far the most common cause, but numerous potentially serious diseases can present with changes of the skin in the diaper area. The differential diagnosis can include psoriasis, metabolic disorders, rare immune diseases and infection. Clinical examination can be helpful in distinguishing the underlying cause. General screening laboratory tests, as well as select testing when a specific condition is suspected, can be used to challenge or confirm the putative diagnosis. PMID:27311780

  5. Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease.

    PubMed

    Maritsi, Despoina N; Zarganis, Diagoras; Metaxa, Zoi; Papaioannou, Georgia; Vartzelis, George

    2013-01-01

    We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent. PMID:23424700

  6. Trichosporon cutaneum (Trichosporon asahii) infection mimicking hand eczema in a patient with leukemia.

    PubMed

    Nakagawa, T; Nakashima, K; Takaiwa, T; Negayama, K

    2000-05-01

    Trichosporon Cutaneum is a yeast-like fungus that causes white piedra and onychomycosis. Recently, it has also been recognized as an opportunistic pathogen in immunocompromised hosts. We describe a 64-year-old woman who developed a superficial Trichosporon infection mimicking hand eczema during chemotherapy for her chronic myelocytic leukemia. To our knowledge, no cases of superficial infection like this one have previously been reported. This case suggests that careful examination is required in diagnosing Trichosporon infection in immunocompromised hosts, because the infection can be invasive or unusual in appearance. PMID:10767708

  7. Malignant mimickers: chronic bacterial and fungal infections of the larynx.

    PubMed

    Klein, Adam M; Tiu, Christopher; Lafreniere, Denis

    2005-03-01

    Chronic infections of the larynx are notorious "copycats" of squamous cell carcinoma. Patients typically present with a historical picture and symptoms identical to those seen in a neoplastic setting: dyspnea, hoarseness, odynophagia, weight loss, and a history of tobacco and alcohol abuse. Historically, these patients were subject to an extensive resection for what was in reality a benign disease. A better understanding and awareness of these conditions has reinforced the need for a direct laryngoscopy, biopsy, and culture in the evaluation of long-lasting laryngeal lesions; this has led to more appropriate and focused treatment. The clinical mimicry of chronic laryngeal infections will be illustrated in two recent case reports, histoplasmosis and botryomycosis of the larynx, which will lead into a discussion on the differential diagnosis of bacterial and fungal laryngeal infections, their evaluation, and treatment options. PMID:15766861

  8. Kerion mimicking bacterial infection in an elderly patient

    PubMed Central

    Ahmad, Sheikh Manzoor; Wani, GH Mohiuddin; Khursheed, Bilques

    2014-01-01

    Tinea capitis is generally thought to be a common disease in children but not in adults. When infection does occur in adults, it may have an atypical appearance. We report an elderly female with inflammatory tinea capitis caused by Trichophyton rubrum. She had numerous pustular lesions throughout the scalp with alopecia, initially treated for bacterial infection. We concluded that tinea capitis should remain in the differential diagnosis of elderly patients with alopecia and pyoderma like presentations and culture test should be routinely done in such patients to avoid complications. PMID:25396139

  9. Yokenella regensburgei infection in India mimicking enteric fever.

    PubMed

    Jain, Sarika; Gaind, Rajni; Gupta, Kunj Bihari; Dawar, Reetika; Kumar, Deepak; Paul, Premila; Sardana, Raman; Deb, Manorama

    2013-06-01

    Yokenella regensburgei is an opportunistic human pathogen of the Enterobacteriaceae family rarely reported to cause human infections. Here, we present a case report of Y. regensburgei bacteraemia from India clinically resembling enteric fever in an apparently immunocompetent paediatric patient. PMID:23518660

  10. Varicella Zoster Infection: A Rare Cause of Abdominal Pain Mimicking Acute Abdomen

    PubMed Central

    Olmez, Deniz; Boz, Alper; Erkan, Nazif

    2009-01-01

    Varicella zoster is an acute viral infection that results from reactivation of a latent varicella zoster virus. It usually occurs in adult population and immune compromised patients. It rarely occurs in healthy children. Here we present a 14 years old male with varicella zoster that had abdominal pain mimicking acute abdomen to alert others who are consulted for the differentiation of acute abdomen and others who may be consulted for pain management. Keywords Varicella zoster; Abdominal pain PMID:22461879

  11. Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male.

    PubMed

    Varnier, Giulia Camilla; Sebire, Neil; Christov, Georgi; Eleftheriou, Despina; Brogan, Paul A

    2016-09-01

    Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition. PMID:27370964

  12. Infection caused by Nocardia farcinica mimicking pulmonary metastasis in an adolescent girl.

    PubMed

    Babayigit, Arzu; Olmez, Duygu; Sozmen, Sule C; Makay, Balahan; Uzuner, Nevin; Karaman, Ozkan; Anal, Ozden; Gulay, Zeynep

    2010-03-01

    Nocardia farcinica infections are rare and potentially life threatening. Herein, we describe a case of pulmonary nocardiosis caused by N. farcinica. This 13-year-old girl admitted with 1-year history of cough, intermittent fever, and recurrent hemoptysis. She was examined for multiple pulmonary nodules mimicking pulmonary metastasis that were detected with chest radiography and computed tomography of the thorax. Eventually, N. farcinica was yielded in culture of sputum and aspiration material of pulmonary nodules. No predisposing factor could be shown for Nocardia infection. Although infections caused by N. farcinica have tendency to disseminate, and are mostly resistant to antibiotics, the patient was successfully treated with prolonged intravenous antibiotic therapy followed with oral amoxicillin-clavulanate. PMID:20216281

  13. Primary Paranasal Tuberculosis in a Diabetic Mimicking Odontogenic Infection: A Rare Case; A Unique Presentation.

    PubMed

    Gupta, Amit; Mehendirratta, Monica; Sareen, Chanchal; Aggarwal, Anju

    2016-03-01

    The incidence of Tuberculosis (TB) is high especially in developing countries but primary para-nasal TB is still a rarity. The latter often remains quiescent until it reaches an advanced stage and offers a diagnostic challenge. In the present case report maxillary sinus TB mimicked a destructive periodontitis induced space infection, thus causing a delay in treatment. The present case report describes clinical presentation, diagnosis, management and outcome of a 50-year-old diabetic/HIV seronegative patient with histopathologically confirmed case of maxillary sinus TB. PMID:27135017

  14. Primary Paranasal Tuberculosis in a Diabetic Mimicking Odontogenic Infection: A Rare Case; A Unique Presentation

    PubMed Central

    Mehendirratta, Monica; Sareen, Chanchal; Aggarwal, Anju

    2016-01-01

    The incidence of Tuberculosis (TB) is high especially in developing countries but primary para-nasal TB is still a rarity. The latter often remains quiescent until it reaches an advanced stage and offers a diagnostic challenge. In the present case report maxillary sinus TB mimicked a destructive periodontitis induced space infection, thus causing a delay in treatment. The present case report describes clinical presentation, diagnosis, management and outcome of a 50-year-old diabetic/HIV seronegative patient with histopathologically confirmed case of maxillary sinus TB. PMID:27135017

  15. Syphilis associated with paretic neurosyphilis mimicking Reiter's syndrome in HIV-infected patients.

    PubMed

    Bastos, Thales Costa; Maia, Daniela Cristina Caetano; Gomes, Nathália Matos; Menezes, Carla Kellen da Silva; Francesconi, Valeska; Francesconi, Fabio

    2015-01-01

    HIV/syphilis co-infection is common because both conditions affect similar risk groups. HIV interferes with the natural history of syphilis, which often has atypical clinical features and nervous system involvement in the early stage of disease. We report the case of an HIV-positive patient with secondary syphilis, scaling palmoplantar keratoderma, scrotal eczema, balanitis and urethritis mimicking Reiter's syndrome. Immunohistochemistry using polyclonal antibodies against Treponema pallidum revealed the presence of spirochetes, associated with the paretic form of parenchymal neurosyphilis. The patient was given crystalline penicillin, with complete resolution of dermatological and neurological symptoms, and no sequelae. PMID:26312720

  16. Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma

    PubMed Central

    Asakura, Takanori; Ishii, Makoto; Kikuchi, Taku; Kameyama, Kaori; Namkoong, Ho; Nakata, Noboru; Sugita, Kayoko; Tasaka, Sadatomo; Shimizu, Takayuki; Hoshino, Yoshihiko; Okamoto, Shinichiro; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Abstract Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma. A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein–Barr virus-encoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because

  17. Cystic teratoma mimicking recurrent pleural effusion, complicated by Mycobacterium abscessus infection

    PubMed Central

    Mohd Radzi, Adli Azam; Bakar, Nor Salmah; Mohd Khalid, Mohd Shukry; Ismail, Ahmad Izuanuddin; Abdul Rani, Mohamed Fauzi

    2016-01-01

    Abstract Teratomas of anterior mediastinum are rare. They are often slow growing, asymptomatic, and detected incidentally on chest imaging. Mycobacterium abscessus (M. abscessus) is an acid‐fast bacillus that is classified as a pathogenic “rapid growing” non‐tuberculous mycobacteria. It is an uncommon cause of human pathology, which may cause skin and soft tissue infection after skin injury following inoculation, minor trauma, and surgery. Here, we present an unusual case of benign cystic teratoma mimicking recurrent pleural effusion, which was subsequently complicated by M. abscessus infection following thoracotomy. Cystic teratoma is rare, but it needs to be considered whenever clinical and investigative work‐up fails to provide a convincing diagnosis. A combined clinical, radiological, surgical, and histopathological assessment is important to arrive at the correct diagnosis. Rapidly growing mycobacteria needs to be included in the differential diagnosis of patients with non‐resolving infected post‐thoracotomy wound and who do not respond to broad‐spectrum antibiotics. PMID:27516884

  18. 18F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma

    PubMed Central

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on 18F-FDG PET/CT mimicked malignant lymphoma. Follow-up 18F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting 18F-FDG PET/CT scans. PMID:27187482

  19. (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma.

    PubMed

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting (18)F-FDG PET/CT scans. PMID:27187482

  20. Widespread and invasive Trichophyton rubrum infection mimicking Kaposi's sarcoma in a patient with AIDS.

    PubMed

    Kwon, Kyung-Sool; Jang, Ho-Sun; Son, Hyo-Sung; Oh, Chang-Keun; Kwon, Yoo-Wook; Kim, Ki-Hong; Suh, Soon-Bong

    2004-10-01

    Opportunistic fungal infections are commonly encountered in AIDS patients. Candidiasis, tinea pedis, onychomycosis, and deep mycotic infections have been the fungal infections most frequently reported in these patients. Dermatophyte infections can appear to be atypical and aggressive in these patients and may lead to a misdiagnosis. We report a Trichophyton rubrum infection in a 44-year-old man with AIDS that presented as a widespread and multiple tumor-like appearance. After the patient was treated with terbinafine for 21 weeks, the lesions cleared completely. We think that this type of dermatophyte infection is very unusual in patients with AIDS and could lead to inappropriate diagnostic processes and treatments. PMID:15672716

  1. Mimicking the host and its microenvironment in vitro for studying mucosal infections by Pseudomonas aeruginosa

    PubMed Central

    Crabbé, Aurélie; Ledesma, Maria A.; Nickerson, Cheryl A.

    2014-01-01

    Why is a healthy person protected from Pseudomonas aeruginosa infections, while individuals with cystic fibrosis or damaged epithelium are particularly susceptible to this opportunistic pathogen? In order to address this question, it is essential to thoroughly understand the dynamic interplay between the host microenvironment and P. aeruginosa. Therefore, using modeI systems that represent key aspects of human mucosal tissues in health and disease allows recreating in vivo host-pathogen interactions in a physiologically relevant manner. In this review, we discuss how factors of mucosal tissues, such as apical-basolateral polarity, junctional complexes, extracellular matrix proteins, mucus, multicellular complexity (including indigenous microbiota), and other physicochemical factors affect P. aeruginosa pathogenesis and are thus important to mimic in vitro. We highlight in vitro cell and tissue culture model systems of increasing complexity that have been used over the past 35 years to study the infectious disease process of P. aeruginosa, mainly focusing on lung models, and their respective advantages and limitations. Continued improvements of in vitro models based on our expanding knowledge of host microenvironmental factors that participate in P. aeruginosa pathogenesis will help advance fundamental understanding of pathogenic mechanisms and increase the translational potential of research findings from bench to the patient’s bedside. PMID:24737619

  2. Candidal Infection of the Gingiva Mimicking Desquamative Gingivitis: A Case Report.

    PubMed

    Yalamanchili, Pallavi Samatha; Potluri, Sushma; Surapaneni, Hemchand; Basha, Md Hafeez; Davanapelly, Pavithra

    2016-03-01

    There has been an increase in the occurrence of fungal infections in humans in the recent years due to the discrete use of broad spectrum antibiotics and immunosuppressive therapies. The genus candida is the most frequently found fungi in humans. Candida albicans is a mucosal microbiota although it can cause infections which can be mucosal or life threatening infections in susceptible individuals. Candidiasis is the most common oral opportunistic fungal infection in humans. Candidiasis usually affects oral mucosa (buccal mucosa) and hard palate. Candidiasis affecting gingiva is not so common, but when it occurs, it is often misdiagnosed as desquamative gingivitis because of its clinical appearance. This paper discusses a case of Candidal infection of gingiva that mimics desquamative gingivitis. PMID:27135011

  3. Candidal Infection of the Gingiva Mimicking Desquamative Gingivitis: A Case Report

    PubMed Central

    Potluri, Sushma; Surapaneni, Hemchand; Basha, Md.Hafeez; Davanapelly, Pavithra

    2016-01-01

    There has been an increase in the occurrence of fungal infections in humans in the recent years due to the discrete use of broad spectrum antibiotics and immunosuppressive therapies. The genus candida is the most frequently found fungi in humans. Candida albicans is a mucosal microbiota although it can cause infections which can be mucosal or life threatening infections in susceptible individuals. Candidiasis is the most common oral opportunistic fungal infection in humans. Candidiasis usually affects oral mucosa (buccal mucosa) and hard palate. Candidiasis affecting gingiva is not so common, but when it occurs, it is often misdiagnosed as desquamative gingivitis because of its clinical appearance. This paper discusses a case of Candidal infection of gingiva that mimics desquamative gingivitis. PMID:27135011

  4. Cutaneous Richter Syndrome mimicking a lower limb cellulitis infection - a case report and review of the literature.

    PubMed

    César, Artur; Calistru, Ana; Pardal, Joana; Magina, Sofia; Mota, Alberto; Azevedo, Filomena

    2016-01-01

    Richter syndrome (RS) is characterized by the development of a high-grade lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Herein, we present the case of an 85-year-old woman with a 3-year history of stable asymptomatic CLL that developed a cutaneous RS. The patient presented with painless inflammation in the left leg and foot that was initially diagnosed as a cellulitis infection. She was treated accordingly with ceftriaxone and clindamycin. However, after completing the antibiotic regimen, not only did the inflammation persist, but also superimposed painless nodules gradually appeared on the left leg and foot over the course of four months. The histopathological examination of the nodules revealed a large B-cell cutaneous lymphoma. The patient underwent chemotherapy with CVP, followed by R-CHOP, resulting in a reduction of size of the nodules and remission of the inflammation. The patient died five months after the diagnosis owing to a bacterial pneumonia. We identified in previous reports a total of fifteen cases of cutaneous RS. Most cases presented with rapidly growing tumors or multiple erythematous nodules, similar to our case. This case of a cutaneous RS mimicking a cellulitis infection underlines the importance of a low threshold for performing biopsies of suspicious skin lesions in patients with CLL/SLL. PMID:27617524

  5. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient.

    PubMed

    Çetinkaya, Erdoğan; Çörtük, Mustafa; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  6. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

    PubMed Central

    Çetinkaya, Erdoğan; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H. Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  7. Invasive mucinous adenocarcinoma mimicking organizing pneumonia associated with Mycobacterium fortuitum infection.

    PubMed

    Morichika, Daisuke; Miyahara, Nobuaki; Hotta, Katsuyuki; Okamoto, Yoshiko; Minami, Daisuke; Irie, Masahiro; Tanimoto, Yasushi; Kanehiro, Arihiko; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-01-01

    We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum. The patient's lung consolidation rapidly progressed; however, repeated bronchoscopy showed no atypical cells, thus suggesting a diagnosis of organizing pneumonia associated with M. fortuitum infection. However, the surgical biopsy specimen was diagnostic for adenocarcinoma, with no mycobacterial infection. Invasive mucinous adenocarcinoma should not be excluded in the differential diagnosis of patients with clinical features of organizing pneumonia and nontuberculous mycobacterium infection, even if a transbronchial biopsy confirms the absence of malignancy. PMID:25500441

  8. Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.

    PubMed

    Pottoo, F H; Bhowmik, M; Vohora, D

    2014-12-18

    Epilepsy in menopausal women presents several challenges in the treatment including an increased risk of seizures due to hormone replacement therapy. We investigated the hypothesis if raloxifene, a selective oestrogen receptor modulator, could be employed to prevent behavioural seizures and morphological alterations in a mouse model mimicking epilepsy in postmenopausal women. Female mice were made ovotoxic by treatment with 4-vinylcyclohexene diepoxide (VCD) to mimic a postmenopausal state. They were then subjected to kainic acid (KA)-induced seizures and neurotoxicity, as assessed by microscopic examination of hippocampus, relevant to human temporal lobe epilepsy. VCD administration (for 15days followed by a drug-free period of 30days) induced ovotoxicity in mice as evidenced by reduced number of primary ovarian follicles. This was accompanied by a 62.4% reduction in serum oestradiol levels. The bone mineral density of ovotoxic mice, however, remained unaffected. Raloxifene (8mg/kg) reduced the seizure severity score in both normal and ovotoxic mice and protected against degeneration induced by KA in the CA3, CA1 sub-fields and hilus of the DG. Hippocampal TGF-β3 levels were not affected by any of the treatments. We show the potential protective role of raloxifene in preventing seizures and neuronal damage in a mouse model mimicking epilepsy in postmenopausal women which was found unrelated to hippocampal TGF-β3. Raloxifene might represent a novel therapeutic option for postmenopausal temporal lobe epileptic woman. PMID:25218046

  9. A case of secondary syphilis mimicking palmoplantar psoriasis in HIV infected patient.

    PubMed

    Bittencourt, Maraya de Jesus Semblano; Brito, Arival Cardoso de; Nascimento, Bianca Angelina Macêdo do; Carvalho, Alessandra Haber; Nascimento, Manoel Dias do

    2015-01-01

    Due to diverse clinical and histopathological presentations, diagnosis of secondary syphilis can occasionally prove challenging. Variable clinical presentations of secondary syphilis in HIV disease may result in an incorrect diagnosis and an inappropriate treatment regimen. Similarly, the histology of secondary syphilitic lesions may show considerable variation, depending on the clinical morphology of the eruption. We report a case of secondary syphilis in an HIV infected patient with cutaneous palmoplantar lesions simulating palmoplantar psoriasis. PMID:26312721

  10. Varicella infection modeling.

    SciTech Connect

    Jones, Katherine A.; Finley, Patrick D.; Moore, Thomas W.; Nozick, Linda Karen; Martin, Nathaniel; Bandlow, Alisa; Detry, Richard Joseph; Evans, Leland B.; Berger, Taylor Eugen

    2013-09-01

    Infectious diseases can spread rapidly through healthcare facilities, resulting in widespread illness among vulnerable patients. Computational models of disease spread are useful for evaluating mitigation strategies under different scenarios. This report describes two infectious disease models built for the US Department of Veteran Affairs (VA) motivated by a Varicella outbreak in a VA facility. The first model simulates disease spread within a notional contact network representing staff and patients. Several interventions, along with initial infection counts and intervention delay, were evaluated for effectiveness at preventing disease spread. The second model adds staff categories, location, scheduling, and variable contact rates to improve resolution. This model achieved more accurate infection counts and enabled a more rigorous evaluation of comparative effectiveness of interventions.

  11. Pattern of circulation of MCMV mimicking natural infection upon oronasal inoculation.

    PubMed

    Zhang, Shunchuan; Xiang, Jun; Desmarets, Lowiese M B; Nauwynck, Hans J

    2016-04-01

    Cytomegaloviruses may infect mammals via oronasal route. However, up till now it remains unclear how this exposure leads to a general infection and shedding. To address this issue, BALB/c female mice were oronasally inoculated with either the highly passaged murine cytomegalovirus (MCMV) Smith or the low passaged MCMV HaNa1. Virus titration showed a productive virus replication of both strains in the nasal mucosa from 1 dpi until the end of the experiment (14 dpi), in lungs from 5 until 14 dpi, and in submandibular glands from 7 until 14 dpi. In contrast to MCMV HaNa1, MCMV Smith also established a low level productive infection in abdominal organs (spleen, liver and kidneys) from 5 dpi (spleen), 7 dpi (liver), and 10 dpi (kidneys) until the end of the experiment. Co-culture showed that for both strains, cell-associated virus was detected in a non-infectious form in nasopharynx-associated lymphoid tissues (NALT) from 1 until 14 dpi, in submandibular lymph nodes from 3 until 5 dpi, in deep cervical lymph nodes from 3 until 14 dpi, in mediastinal lymph nodes from 7 until 14 dpi, in spleen from 5 until at least 10 dpi and in the peripheral blood mononuclear cells (PBMC) at 7 and 10 dpi. The present study shows that upon oronasal exposure, MCMV first enters the nasal mucosa and NALT, from where the virus disseminates to the spleen possibly via the draining lymphatic system and blood; a subsequent cell-associated viremia transports MCMV to submandibular glands and for MCMV Smith also to liver and kidneys, where a second productive replication starts. PMID:26732487

  12. Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites

    PubMed Central

    Durnaś, Bonita; Wnorowska, Urszula; Pogoda, Katarzyna; Deptuła, Piotr; Wątek, Marzena; Piktel, Ewelina; Głuszek, Stanisław; Gu, Xiaobo; Savage, Paul B.; Niemirowicz, Katarzyna; Bucki, Robert

    2016-01-01

    Fungal infections, especially those caused by antibiotic resistant pathogens, have become a serious public health problem due to the growing number of immunocompromised patients, including those subjected to anticancer treatment or suffering from HIV infection. In this study we assessed fungicidal activity of the ceragenins CSA-13, CSA-131 and CSA-192 against four fluconazole–resistant Candida strains. We found that ceragenins activity against planktonic Candida cells was higher than activity of human LL-37 peptide and synthetic cationic peptide omiganan. Compared to LL-37 peptide, ceragenins in the presence of DNase I demonstrated an increased ability to kill DNA-induced Candida biofilm. Microscopy studies show that treatment with LL-37 or ceragenins causes Candida cells to undergo extensive surface changes indicating surface membrane damage. This conclusion was substantiated by observation of rapid incorporation of FITC-labeled CSA-13, CSA-131 or LL-37 peptide into the more lipophilic environment of the Candida membrane. In addition to activity against Candida spp., ceragenins CSA-131 and CSA-192 display strong fungicidal activity against sixteen clinical isolates including Cryptococcus neoformans and Aspergillus fumigatus. These results indicate the potential of ceragenins for future development as new fungicidal agents. PMID:27315208

  13. Pyoderma Gangrenosum Mimicking an Infected Wound following Dynamic Hip Screw Fixation

    PubMed Central

    Nizamoglu, Metin

    2015-01-01

    Pyoderma gangrenosum (PG) is an inflammatory ulcerative neutrophilic dermatosis that can occur following skin trauma. The correct diagnosis is not often made immediately as the condition can mimic an infective appearance. This leads to delays in the appropriate management of high dose steroids. Although debridement can offer aid in resolving lesions, this is contraindicated in the acute phase as this can cause acceleration of the pathogenic process. Biopsy of the lesion does not offer a definitive diagnosis; therefore suspicion must be maintained as the diagnosis is ultimately a clinical one. Any postoperative pustular ulcerative lesion not improving despite antibiotic therapy that also yields negative bacteriological and fungal studies should lead to consideration of this diagnosis. We document the first case of PG developing following intertrochanteric femur fracture fixation using dynamic hip screw. PMID:26380139

  14. Modeling intraocular bacterial infections.

    PubMed

    Astley, Roger A; Coburn, Phillip S; Parkunan, Salai Madhumathi; Callegan, Michelle C

    2016-09-01

    Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease. PMID:27154427

  15. Urinary tract infection of mice to model human disease: Practicalities, implications and limitations.

    PubMed

    Carey, Alison J; Tan, Chee K; Ipe, Deepak S; Sullivan, Matthew J; Cripps, Allan W; Schembri, Mark A; Ulett, Glen C

    2016-09-01

    Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Murine models of human UTI are vital experimental tools that have helped to elucidate UTI pathogenesis and advance knowledge of potential treatment and infection prevention strategies. Fundamentally, several variables are inherent in different murine models, and understanding the limitations of these variables provides an opportunity to understand how models may be best applied to research aimed at mimicking human disease. In this review, we discuss variables inherent in murine UTI model studies and how these affect model usage, data analysis and data interpretation. We examine recent studies that have elucidated UTI host-pathogen interactions from the perspective of gene expression, and review new studies of biofilm and UTI preventative approaches. We also consider potential standards for variables inherent in murine UTI models and discuss how these might expand the utility of models for mimicking human disease and uncovering new aspects of pathogenesis. PMID:26006172

  16. Large B-cell lymphoma mimicking iliopsoas abscess following open revision of proximal femur infected non-union: a case report

    PubMed Central

    2014-01-01

    Background Extranodal presentation of lymphoma is a rare occurrence. It has been postulated that chronic antigen stimulation may predispose a patient to the development of lymphoma. Case presentation We present a case report of a large extranodal B-cell lymphoma mimicking a postoperative abscess following surgery for an infected proximal femur nonunion in an 80-year-old Caucasian male of Italian descent. Conclusions This case highlights the need to consider malignancy in revision surgery, careful examination of operative specimens and the need for further understanding of the role of metal implants in chronic antigen stimulation. PMID:25056400

  17. A blood-mimicking fluid for particle image velocimetry with silicone vascular models

    NASA Astrophysics Data System (ADS)

    Yousif, Majid Y.; Holdsworth, David W.; Poepping, Tamie L.

    2011-03-01

    For accurate particle image velocimetry measurements in hemodynamics studies, it is important to use a fluid with a refractive index ( n) matching that of the vascular models (phantoms) and ideally a dynamic viscosity matching human blood. In this work, a blood-mimicking fluid (BMF) composed of water, glycerol, and sodium iodide was formulated for a range of refractive indices to match most common silicone elastomers ( n = 1.40-1.43) and with corresponding dynamic viscosity within the average cited range of healthy human blood (4.4 ± 0.5 cP). Both refractive index and viscosity were attained at room temperature (22.2 ± 0.2°C), which eliminates the need for a temperature-control system. An optimally matched BMF, suitable for use in a vascular phantom ( n = 1.4140 ± 0.0008, Sylgard 184), was demonstrated with composition (by weight) of 47.38% water, 36.94% glycerol (44:56 glycerol-water ratio), and 15.68% sodium iodide salt, resulting in a dynamic viscosity of 4 .31 ± 0 .03 cP.

  18. Biorelevant media resistant co-culture model mimicking permeability of human intestine.

    PubMed

    Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

    2015-03-15

    Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. PMID:25601199

  19. A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

    PubMed

    Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

    2016-06-30

    Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions. PMID:26924647

  20. Key role of magnetic resonance imaging in the diagnosis of infections around the hip and pelvic girdle mimicking septic arthritis of the hip in children.

    PubMed

    Song, Kwang Soon; Lee, Si Wook; Bae, Ki Cheor

    2016-05-01

    Infections around the hip and the pelvic girdle mimicking septic hip arthritis are rare conditions in the pediatric population requiring urgent treatment. They are not readily diagnosed because of rarity, resemblance to septic hip, and unclear pathophysiology, which often results in misdiagnosis, delayed diagnosis, and delayed treatment. The aim of this study was to prove the key role of magnetic resonance imaging (MRI) as the first-line modality in making a early definite diagnosis of an uncommon perihip infection in children. We retrospectively reviewed 20 children with a provisional diagnosis of unilateral septic hip who were confirmed finally to have perihip infections and combined with concomitant osteomyeltis using MRI. All patients were treated with intravenous antibiotics with or without abscess aspiration until normalization of clinical symptoms and laboratory tests including serum C-reactive protein and erythrocyte sedimentation rate. All infections healed successfully and the final C-reactive protein was recovered to a mean of 0.37 mg/dl (range 0.01-0.78 mg/dl) without recurrence or complication. Although the MRI is costly and limited in practical application, it was found to be effective as a primary diagnostic tool for an early, accurate diagnosis of infections around the hip and the pelvic girdle in children to correctly guide the decision and the approach for treatment. PMID:27007545

  1. Urticaria mimickers in children.

    PubMed

    Mathur, Anubhav N; Mathes, Erin F

    2013-01-01

    Acute urticaria is a self-limited cutaneous condition marked by transient, erythematous, and pruritic wheals. It is a hypersensitivity response that is often secondary to infection, medications, or food allergies in children. In contrast, the urticarial "mimickers" described in this review article are often seen in the context of fever and extracutaneous manifestations in pediatric patients. The differential diagnosis ranges from benign and self-limited hypersensitivity responses to multisystem inflammatory diseases. Establishing the correct diagnosis of an urticarial rash in a pediatric patient is necessary to both prevent an unnecessary work up for self-limited conditions and to appropriately recognize and evaluate multisystem inflammatory disorders. Herein, we describe two cases to illustrate the clinical manifestations, laboratory findings, histopathology and differential diagnoses for several mimickers of acute urticaria including: urticaria multiforme, serum sickness like reaction, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, systemic onset juvenile idiopathic arthritis, cryopyrin associated periodic syndromes, and urticarial vasculitis. PMID:24552410

  2. The 18F-FDG PET/CT finding of a condyloma acuminata mimicking primary anorectal carcinoma in an HIV-infected patient.

    PubMed

    Kim, Bom Sahn

    2013-10-01

    This case report describes a condyloma acuminata with intense FDG uptake mimicking primary anorectal carcinoma in an HIV-infected patient.A 44-year-old HIV-positive homosexual man with a history of lymphoma underwent an 18F-FDG PET/CT for restaging. A focal intense hypermetabolic lesion around the anorectal area was found by the PET/CT and it was suggested as a tumorous lesion. However, the lesion was not detected on the contrast-enhanced abdominal CT. Via a sigmoidoscopy, cauliflower-like masses were visualized in the intra-anal area. The tumor was surgically excised and proven to be condyloma acuminata by permanent pathology. PMID:22996249

  3. Epicutaneous model of community-acquired Staphylococcus aureus skin infections.

    PubMed

    Prabhakara, Ranjani; Foreman, Oded; De Pascalis, Roberto; Lee, Gloria M; Plaut, Roger D; Kim, Stanley Y; Stibitz, Scott; Elkins, Karen L; Merkel, Tod J

    2013-04-01

    Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T(h)1 and T(h)17 cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection. PMID:23381997

  4. Disseminated Cryptococcal infection in an immunocompetent host mimicking plasma cell disorder: a case report and literature review

    PubMed Central

    Abid, Muhammad Bilal; De Mel, Sanjay; Limei, Michelle Poon

    2015-01-01

    Key Clinical Message Cryptococcosis is a potentially fatal fungal infection caused mainly by Cryptocococcus neoformans (CN) species and it rarely infects immunocompetent hosts. The outcomes are better only if the condition is suspected and diagnosed early and treatment is instituted. PMID:25984313

  5. Pulmonary Mycobacterium kansasii Infection Mimicking Malignancy on the 18F-FDG PET Scan in a Patient Receiving Etanercept: A Case Report and Literature Review

    PubMed Central

    Amlani, Mohan

    2014-01-01

    A 66-year-old male presented with chest pain, malaise, generalized weakness, and weight loss. He had been receiving etanercept injection for rheumatoid arthritis. Chest X-ray revealed a right upper lobe mass. Chest computed tomography (CT) showed a right apical mass, highly suggestive of a Pancoast tumor. The thoracic fluorine-18 fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) scan demonstrated significantly high metabolic pulmonary lesions with the standardized uptake value (SUV) of 12.5, consistent with lung cancer. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL). BAL cytology was negative for malignant cells. BAL acid fast bacilli (AFB) smears were positive, and Mycobacterium kansasii was eventually isolated. He received a 12-month course of rifampin, isoniazid, and ethambutol. Interval resolution of pulmonary lesions was noted on follow-up serial CT chest studies. There has been increasing incidence of nontuberculous mycobacterial infections reported in patients treated with the antitumor necrosis factor-alpha (anti-TNF-alpha) agents. Infectious foci have an increased glucose metabolism which potentially causes a high FDG uptake on the 18F-FDG PET scan, leading to undue anxiety and cost to the patients. This is the first reported case of pulmonary M. kansasii infection with a positive thoracic 18F-FDG PET study mimicking malignancy in a patient on etanercept. PMID:25389506

  6. Proposed Pharmacological Countermeasures Against Apoptotic Cell Death in Experimental Models Mimicking Space Environment Damage

    NASA Astrophysics Data System (ADS)

    Lulli, Matteo; Papucci, Laura; Witort, Ewa; Donnini, Martino; Lapucci, Andrea; Lazzarano, Stefano; Mazzoni, Tiziano; Simoncini, Madine; Falciani, Piergiuseppe; Capaccioli, Sergio

    2008-06-01

    Several damaging agents have been suggested to affect human vision during long term space travels. Recently, apoptosis induced by DNA-damaging agents has emerged as frequent pathogenetic mechanism of ophthalmologic pathologies. Here, we propose two countermeasures: coenzyme Q10 and bcl-2 downregulation preventing antisense oligoribonucleotides (ORNs), aimed to inhibit cellular apoptotic death. Our studies have been carried out on retina and neuronal cultured cells treated with the following apoptotic stimuli mimicking space environment: a several-day exposure to either 3H-labeled tymidine or to the genotoxic drug doxorubicin, UV irradiation, hypoxia and glucose/growth factor starvation (Locke medium). The preliminary results clearly indicate that CoQ10, as well as bcl-2 down-regulation preventing ORNs, significantly counteract apoptosis in response to different DNA damaging agents in cultured eye and in neuronal cells. This supports the possibility that both could be optimal countermeasures against ophthalmologic lesions during space explorations.

  7. Study of optical clearing in polarization measurements by Monte Carlo simulations with anisotropic tissue-mimicking models.

    PubMed

    Chen, Dongsheng; Zeng, Nan; Wang, Yunfei; He, Honghui; Tuchin, Valery V; Ma, Hui

    2016-08-01

    We conducted Monte Carlo simulations based on anisotropic sclera-mimicking models to examine the polarization features in Mueller matrix polar decomposition (MMPD) parameters during the refractive index matching process, which is one of the major mechanisms of optical clearing. In a preliminary attempt, by changing the parameters of the models, wavelengths, and detection geometries, we demonstrate how the depolarization coefficient and retardance vary during the refractive index matching process and explain the polarization features using the average value and standard deviation of scattering numbers of the detected photons. We also study the depth-resolved polarization features during the gradual progression of the refractive index matching process. The results above indicate that the refractive index matching process increases the depth of polarization measurements and may lead to higher contrast between tissues of different anisotropies in deeper layers. MMPD-derived polarization parameters can characterize the refractive index matching process qualitatively. PMID:27240298

  8. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  9. Rabbit model of rotavirus infection.

    PubMed Central

    Conner, M E; Estes, M K; Graham, D Y

    1988-01-01

    A new small animal model was developed to study parameters of rotavirus infections, including the active immune response. Seronegative New Zealand White rabbits (neonatal to 4 months old) were inoculated orally with cultivatable rabbit rotavirus strains Ala, C11, and R2 and with the heterologous simian strain SA11. The course of infection was evaluated by clinical findings, virus isolation (plaque assay and enzyme-linked immunosorbent assay), and serologic response. All four strains of virus were capable of infecting rabbits as determined by isolation of infectious virus from intestinal contents or fecal samples, by seroconversion, or by a combination of these methods. The responses differed depending on the virus strain used for inoculation. Rabbits remained susceptible to primary infection to at least 16 weeks of age (upper limit examined). Virus excretion in intestinal contents was detected from 6 h to 7 days postinoculation. RNA electropherotypes of inocula and viruses isolated from rabbits were the same in all samples tested. Transmission of Ala virus and R2 virus but not SA11 virus from inoculated animals to uninoculated controls also occurred. In a challenge experiment with Ala virus, 74- and 90-day-old rabbits were rechallenged with Ala 5 weeks after a primary infection with Ala. Virus was excreted in feces from 2 to 8 days after the primary infection but was not excreted after challenge. These results indicate that the rabbit provides an ideal model to investigate both the primary and secondary active immune responses to rotavirus infections and to evaluate candidate vaccines. Images PMID:2833612

  10. Constraints from growth-rate data on some coupled dark energy models mimicking a ΛCDM expansion

    NASA Astrophysics Data System (ADS)

    Fay, Stéphane

    2016-05-01

    The ΛCDM expansion could be mimicked by a dark energy coupled to matter. Then, the equation of state bar{w} and coupling bar{Q} of this coupled dark energy could not be constrained by observations of the Hubble function alone. Also, in this paper, we determine the constraints on two such coupled dark energy models considering some current and forecast Euclid-like growth-rate data and assuming the prior on the ΛCDM dark matter density parameter today Ωm0 = 0.295 ± 0.04. The first model is defined by a constant equation of state. We find that at 2σ, bar{w}=-1.02_{-0.22}^{+0.06} and the coupling function bar{Q}_0 today is bar{Q}_0H_0^{-3}=0.057_{-0.148}^{+0.353} with H0 the Hubble constant. The second model is defined by a varying equation of state bar{w}=bar{w}_a-bar{w}_bln (1+z), with z the redshift and (bar{w}_a,bar{w}_b), two constants. We find that at 2σ, bar{w}_a=-0.99_{-0.90}^{+0.17}, bar{w}_b=-0.04_{-1.17}^{+0.31} and bar{Q}_0H_0^{-3}=0.0002_{-0.18}^{+1.35}. These constraints on coupled dark energy agreed with a ΛCDM model but are too poor to discard confidently a coupled dark energy different from vacuum but mimicking a ΛCDM expansion.

  11. Constraints from growth-rate data on some coupled dark energy models mimicking a ΛCDM expansion

    NASA Astrophysics Data System (ADS)

    Fay, Stéphane

    2016-08-01

    The ΛCDM expansion can be mimicked by dark energy coupled to matter. In this case, the equation of state bar{w} and coupling bar{Q} of this coupled dark energy cannot be constrained by observations of the Hubble function alone. In this article, we determine the constraints on two such coupled dark energy models, considering some current and forecast Euclid-like growth-rate data and assuming the prior on the ΛCDM dark matter density parameter today, Ωm0 = 0.295 ± 0.04. The first model is defined by a constant equation of state. We find that, at 2σ, bar{w}=-1.02_{-0.22}^{+0.06} and the coupling function bar{Q}_0 today is bar{Q}_0H_0^{-3}=0.057_{-0.148}^{+0.353}, with H0 the Hubble constant. The second model is defined by a varying equation of state bar{w}=bar{w}_a-bar{w}_bln (1+z), with z the redshift and (bar{w}_a,bar{w}_b) two constants. We find that, at 2σ, bar{w}_a=-0.99_{-0.90}^{+0.17}, bar{w}_b=-0.04_{-1.17}^{+0.31} and bar{Q}_0H_0^{-3}=0.0002_{-0.18}^{+1.35}. These constraints on coupled dark energy agree with a ΛCDM model but are too poor to discard with confidence coupled dark energy different from a vacuum but mimicking a ΛCDM expansion.

  12. Modeling Zika Virus Infection in Mice.

    PubMed

    Rossi, Shannan L; Vasilakis, Nikos

    2016-07-01

    Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly. PMID:27392219

  13. A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus

    PubMed Central

    Wang, Xiang-Yu; Huang, Zhao-Xia; Chen, Yi-Guo; Lu, Xiao; Zhu, Ping; Wen, Kun; Fu, Ning; Liu, Bei-Yi

    2015-01-01

    Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ+CD3+ T cells and IL-17+CD4+ T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus. PMID:26317210

  14. Antibacterial metabolites secreted under glucose-limited environment of the mimicked proximal colon model by lactobacilli abundant in infant feces.

    PubMed

    Kanjan, Pochanart; Hongpattarakere, Tipparat

    2016-09-01

    The most abundance of anti-Salmonella lactic acid bacteria (LAB) was found in feces of naturally born, exclusively breastfed Thai infants. Six strains of Lactobacillus plantarum and one strain of Lactobacillus paracasei were selected and identified. In the co-cultivation assay, L. plantarum subsp. plantarum I62 showed the strongest and broadest antibacterial activity against Escherichia coli, Shigella sonnei, Salmonella Paratyphi A, and Salmonella Typhimurium SA 2093 under the mimicked proximal colon condition, in which glucose and other nutrients were limited. According to GC-MS analysis, the major antibacterial contribution of organic acids secreted by L. plantarum I62 grown in the presence of glucose was dramatically reduced from 95.8 to 41.9 % under glucose-limited niche. The production of low-pK a acids, such as lactic, 1,2-benzenedicarboxylic, and 3-phenyllactic acids, was remarkably dropped. Surprisingly, higher-pK a acids such as 5-chlorobenzimidazole-2-carboxylic, pyroglutamic, palmitic, and oleic acids were enhanced. Moreover, cyclic dipeptides, ketones, alkanes, alcohols, and miscellaneous compounds, which were pH-independent antibacterial metabolites, became dominant. The electron microscopy strongly supported the synergistic attacks of the multiple antibacterial components targeting outer and cytoplasmic membranes leading to severe leakage and cell disruption of Salmonella Typhimurium. This strain poses to be a potential probiotic candidate for effectively controlling and treating human foodborne bacterial infection. PMID:27188778

  15. Stochastic models of viral infection

    NASA Astrophysics Data System (ADS)

    Chou, Tom

    2009-03-01

    We develop biophysical models of viral infections from a stochastic process perspective. The entry of enveloped viruses is treated as a stochastic multiple receptor and coreceptor engagement process that can lead to membrane fusion or endocytosis. The probabilities of entry via fusion and endocytosis are computed as functions of the receptor/coreceptor engagement rates. Since membrane fusion and endocytosis entry pathways can lead to very different infection outcomes, we delineate the parameter regimes conducive to each entry pathway. After entry, viral material is biochemically processed and degraded as it is transported towards the nucleus. Productive infections occur only when the material reaches the nucleus in the proper biochemical state. Thus, entry into the nucleus in an infectious state requires the proper timing of the cytoplasmic transport process. We compute the productive infection probability and show its nonmonotonic dependence on both transport speeds and biochemical transformation rates. Our results carry subtle consequences on the dosage and efficacy of antivirals such as reverse transcription inhibitors.

  16. Human Liver Infection in a Dish: Easy-To-Build 3D Liver Models for Studying Microbial Infection

    PubMed Central

    Petropolis, Debora B.; Faust, Daniela M.; Tolle, Matthieu; Rivière, Lise; Valentin, Tanguy; Neuveut, Christine; Hernandez-Cuevas, Nora; Dufour, Alexandre; Olivo-Marin, Jean-Christophe; Guillen, Nancy

    2016-01-01

    Human liver infection is a major cause of death worldwide, but fundamental studies on infectious diseases affecting humans have been hampered by the lack of robust experimental models that accurately reproduce pathogen-host interactions in an environment relevant for the human disease. In the case of liver infection, one consequence of this absence of relevant models is a lack of understanding of how pathogens cross the sinusoidal endothelial barrier and parenchyma. To fill that gap we elaborated human 3D liver in vitro models, composed of human liver sinusoidal endothelial cells (LSEC) and Huh-7 hepatoma cells as hepatocyte model, layered in a structure mimicking the hepatic sinusoid, which enable studies of key features of early steps of hepatic infection. Built with established cell lines and scaffold, these models provide a reproducible and easy-to-build cell culture approach of reduced complexity compared to animal models, while preserving higher physiological relevance compared to standard 2D systems. For proof-of-principle we challenged the models with two hepatotropic pathogens: the parasitic amoeba Entamoeba histolytica and hepatitis B virus (HBV). We constructed four distinct setups dedicated to investigating specific aspects of hepatic invasion: 1) pathogen 3D migration towards hepatocytes, 2) hepatocyte barrier crossing, 3) LSEC and subsequent hepatocyte crossing, and 4) quantification of human hepatic virus replication (HBV). Our methods comprise automated quantification of E. histolytica migration and hepatic cells layer crossing in the 3D liver models. Moreover, replication of HBV virus occurs in our virus infection 3D liver model, indicating that routine in vitro assays using HBV or others viruses can be performed in this easy-to-build but more physiological hepatic environment. These results illustrate that our new 3D liver infection models are simple but effective, enabling new investigations on infectious disease mechanisms. The better

  17. Human Liver Infection in a Dish: Easy-To-Build 3D Liver Models for Studying Microbial Infection.

    PubMed

    Petropolis, Debora B; Faust, Daniela M; Tolle, Matthieu; Rivière, Lise; Valentin, Tanguy; Neuveut, Christine; Hernandez-Cuevas, Nora; Dufour, Alexandre; Olivo-Marin, Jean-Christophe; Guillen, Nancy

    2016-01-01

    Human liver infection is a major cause of death worldwide, but fundamental studies on infectious diseases affecting humans have been hampered by the lack of robust experimental models that accurately reproduce pathogen-host interactions in an environment relevant for the human disease. In the case of liver infection, one consequence of this absence of relevant models is a lack of understanding of how pathogens cross the sinusoidal endothelial barrier and parenchyma. To fill that gap we elaborated human 3D liver in vitro models, composed of human liver sinusoidal endothelial cells (LSEC) and Huh-7 hepatoma cells as hepatocyte model, layered in a structure mimicking the hepatic sinusoid, which enable studies of key features of early steps of hepatic infection. Built with established cell lines and scaffold, these models provide a reproducible and easy-to-build cell culture approach of reduced complexity compared to animal models, while preserving higher physiological relevance compared to standard 2D systems. For proof-of-principle we challenged the models with two hepatotropic pathogens: the parasitic amoeba Entamoeba histolytica and hepatitis B virus (HBV). We constructed four distinct setups dedicated to investigating specific aspects of hepatic invasion: 1) pathogen 3D migration towards hepatocytes, 2) hepatocyte barrier crossing, 3) LSEC and subsequent hepatocyte crossing, and 4) quantification of human hepatic virus replication (HBV). Our methods comprise automated quantification of E. histolytica migration and hepatic cells layer crossing in the 3D liver models. Moreover, replication of HBV virus occurs in our virus infection 3D liver model, indicating that routine in vitro assays using HBV or others viruses can be performed in this easy-to-build but more physiological hepatic environment. These results illustrate that our new 3D liver infection models are simple but effective, enabling new investigations on infectious disease mechanisms. The better

  18. Validation of a sensitive DNA walking strategy to characterise unauthorised GMOs using model food matrices mimicking common rice products.

    PubMed

    Fraiture, Marie-Alice; Herman, Philippe; Taverniers, Isabel; De Loose, Marc; Van Nieuwerburgh, Filip; Deforce, Dieter; Roosens, Nancy H

    2015-04-15

    To identify unauthorised GMOs in food and feed matrices, an integrated approach has recently been developed targeting pCAMBIA family vectors, highly present in transgenic plants. Their presence is first assessed by qPCR screening and is subsequently confirmed by characterising the transgene flanking regions, using DNA walking. Here, the DNA walking performance has been thoroughly tested for the first time, regarding the targeted DNA quality and quantity. Several assays, on model food matrices mimicking common rice products, have allowed to determine the limit of detection as well as the potential effects of food mixture and processing. This detection system allows the identification of transgenic insertions as low as 10 HGEs and was not affected by the presence of untargeted DNA. Moreover, despite the clear impact of food processing on DNA quality, this method was able to cope with degraded DNA. Given its specificity, sensitivity, reliability, applicability and practicability, the proposed approach is a key detection tool, easily implementable in enforcement laboratories. PMID:25466152

  19. A fractional-order infectivity SIR model

    NASA Astrophysics Data System (ADS)

    Angstmann, C. N.; Henry, B. I.; McGann, A. V.

    2016-06-01

    Fractional-order SIR models have become increasingly popular in the literature in recent years, however unlike the standard SIR model, they often lack a derivation from an underlying stochastic process. Here we derive a fractional-order infectivity SIR model from a stochastic process that incorporates a time-since-infection dependence on the infectivity of individuals. The fractional derivative appears in the generalised master equations of a continuous time random walk through SIR compartments, with a power-law function in the infectivity. We show that this model can also be formulated as an infection-age structured Kermack-McKendrick integro-differential SIR model. Under the appropriate limit the fractional infectivity model reduces to the standard ordinary differential equation SIR model.

  20. Towards multiscale modeling of influenza infection

    PubMed Central

    Murillo, Lisa N.; Murillo, Michael S.; Perelson, Alan S.

    2013-01-01

    Aided by recent advances in computational power, algorithms, and higher fidelity data, increasingly detailed theoretical models of infection with influenza A virus are being developed. We review single scale models as they describe influenza infection from intracellular to global scales, and, in particular, we consider those models that capture details specific to influenza and can be used to link different scales. We discuss the few multiscale models of influenza infection that have been developed in this emerging field. In addition to discussing modeling approaches, we also survey biological data on influenza infection and transmission that is relevant for constructing influenza infection models. We envision that, in the future, multiscale models that capitalize on technical advances in experimental biology and high performance computing could be used to describe the large spatial scale epidemiology of influenza infection, evolution of the virus, and transmission between hosts more accurately. PMID:23608630

  1. Accelerating expansion or inhomogeneity? II. Mimicking acceleration with the energy function in the Lemaître-Tolman model

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-07-01

    This is a continuation of the paper published in Phys. Rev. D 89, 023520 (2014). Here we investigate how the luminosity distance-redshift relation DL(z) of the ΛCDM model is duplicated in the Lemaître-Tolman (L-T) model with Λ =0, constant bang-time function tB and the energy function E(r) mimicking accelerated expansion on the observer's past light cone (r is a uniquely defined comoving radial coordinate). Numerical experiments show that E>0 necessarily. The functions z(r) and E(r) are numerically calculated from the initial point at the observer's position, then backward from the initial point at the apparent horizon (AH). Reconciling the results of the two calculations allows one to determine the values of E/r2 at r=0 and at the AH. The problems connected with continuing the calculation through the AH are discussed in detail and solved. Then z(r) and E(r) are continued beyond the AH, up to the numerical crash that signals the contact of the light cone with the big bang. Similarly, the light cone of the L-T model is calculated by proceeding from the two initial points, and compared with the ΛCDM light cone. The model constructed here contains shell crossings, but they can be removed by matching the L-T region to a Friedmann background, without causing any conflict with the type Ia supernovae observations. The mechanism of imitating the accelerated expansion by the E(r) function is explained in a descriptive way.

  2. Micro-scale finite element modeling of ultrasound propagation in aluminum trabecular bone-mimicking phantoms: A comparison between numerical simulation and experimental results.

    PubMed

    Vafaeian, B; Le, L H; Tran, T N H T; El-Rich, M; El-Bialy, T; Adeeb, S

    2016-05-01

    The present study investigated the accuracy of micro-scale finite element modeling for simulating broadband ultrasound propagation in water-saturated trabecular bone-mimicking phantoms. To this end, five commercially manufactured aluminum foam samples as trabecular bone-mimicking phantoms were utilized for ultrasonic immersion through-transmission experiments. Based on micro-computed tomography images of the same physical samples, three-dimensional high-resolution computational samples were generated to be implemented in the micro-scale finite element models. The finite element models employed the standard Galerkin finite element method (FEM) in time domain to simulate the ultrasonic experiments. The numerical simulations did not include energy dissipative mechanisms of ultrasonic attenuation; however, they expectedly simulated reflection, refraction, scattering, and wave mode conversion. The accuracy of the finite element simulations were evaluated by comparing the simulated ultrasonic attenuation and velocity with the experimental data. The maximum and the average relative errors between the experimental and simulated attenuation coefficients in the frequency range of 0.6-1.4 MHz were 17% and 6% respectively. Moreover, the simulations closely predicted the time-of-flight based velocities and the phase velocities of ultrasound with maximum relative errors of 20 m/s and 11 m/s respectively. The results of this study strongly suggest that micro-scale finite element modeling can effectively simulate broadband ultrasound propagation in water-saturated trabecular bone-mimicking structures. PMID:26894840

  3. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

    Streptococcal pathogens cause a wide array of clinical syndromes in humans, including invasive systemic infections resulting in high mortality rates. Many of these pathogens are human specific, and therefore difficult to analyze in vivo using typical animal models, as these models rarely replicate what is observed in human infections. This unit describes the use of the zebrafish (Danio rerio) as an animal model for streptococcal infection to analyze multiple disease states. This model closely mimics the necrotizing fasciitis/myositis pathology observed in humans from a Streptococcus pyogenes infection. The use of a zoonotic pathogen, Streptococcus iniae, which replicates systemic infections caused by many streptococcal pathogens, including dissemination to the brain, is also described. Included protocols describe both intraperitoneal and intramuscular infections, as well as methods for histological and quantitative measurements of infection. PMID:19412913

  4. Mouse Models for Filovirus Infections

    PubMed Central

    Bradfute, Steven B.; Warfield, Kelly L.; Bray, Mike

    2012-01-01

    The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs), guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data), but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study. PMID:23170168

  5. Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet

    PubMed Central

    Pearce, D. J. G.; Turner, M. S.

    2015-01-01

    Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines. PMID:26423438

  6. Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet.

    PubMed

    Pearce, D J G; Turner, M S

    2015-10-01

    Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines. PMID:26423438

  7. Closed traumatic brain injury model in sheep mimicking high-velocity, closed head trauma in humans.

    PubMed

    Grimmelt, A-C; Eitzen, S; Balakhadze, I; Fischer, B; Wölfer, J; Schiffbauer, H; Gorji, A; Greiner, C

    2011-08-01

    To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves

  8. Modeling the three stages in HIV infection.

    PubMed

    Hernandez-Vargas, Esteban A; Middleton, Richard H

    2013-03-01

    A typical HIV infection response consists of three stages: an initial acute infection, a long asymptomatic period and a final increase in viral load with simultaneous collapse in healthy CD4+T cell counts. The majority of existing mathematical models give a good representation of either the first two stages or the last stage of the infection. Using macrophages as a long-term active reservoir, a deterministic model is proposed to explain the three stages of the infection including the progression to AIDS. Simulation results illustrate how chronic infected macrophages can explain the progression to AIDS provoking viral explosion. Further simulation studies suggest that the proposed model retains its key properties even under moderately large parameter variations. This model provides important insights on how macrophages might play a crucial role in the long term behavior of HIV infection. PMID:23238280

  9. Animal models of external traumatic wound infections

    PubMed Central

    Dai, Tianhong; Kharkwal, Gitika B; Tanaka, Masamitsu; Huang, Ying-Ying; Bil de Arce, Vida J

    2011-01-01

    Background: Despite advances in traumatic wound care and management, infections remain a leading cause of mortality, morbidity and economic disruption in millions of wound patients around the world. Animal models have become standard tools for studying a wide array of external traumatic wound infections and testing new antimicrobial strategies. Results: Animal models of external traumatic wound infections reported by different investigators vary in animal species used, microorganism strains, the number of microorganisms applied, the size of the wounds and for burn infections, the length of time the heated object or liquid is in contact with the skin. Methods: This review covers experimental infections in animal models of surgical wounds, skin abrasions, burns, lacerations, excisional wounds and open fractures. Conclusions: As antibiotic resistance continues to increase, more new antimicrobial approaches are urgently needed. These should be tested using standard protocols for infections in external traumatic wounds in animal models. PMID:21701256

  10. Reconstituting ring-rafts in bud-mimicking topography of model membranes

    NASA Astrophysics Data System (ADS)

    Ryu, Yong-Sang; Lee, In-Ho; Suh, Jeng-Hun; Park, Seung Chul; Oh, Soojung; Jordan, Luke R.; Wittenberg, Nathan J.; Oh, Sang-Hyun; Jeon, Noo Li; Lee, Byoungho; Parikh, Atul N.; Lee, Sin-Doo

    2014-07-01

    During vesicular trafficking and release of enveloped viruses, the budding and fission processes dynamically remodel the donor cell membrane in a protein- or a lipid-mediated manner. In all cases, in addition to the generation or relief of the curvature stress, the buds recruit specific lipids and proteins from the donor membrane through restricted diffusion for the development of a ring-type raft domain of closed topology. Here, by reconstituting the bud topography in a model membrane, we demonstrate the preferential localization of cholesterol- and sphingomyelin-enriched microdomains in the collar band of the bud-neck interfaced with the donor membrane. The geometrical approach to the recapitulation of the dynamic membrane reorganization, resulting from the local radii of curvatures from nanometre-to-micrometre scales, offers important clues for understanding the active roles of the bud topography in the sorting and migration machinery of key signalling proteins involved in membrane budding.

  11. Reconstituting ring-rafts in bud-mimicking topography of model membranes

    PubMed Central

    Ryu, Yong-Sang; Lee, In-Ho; Suh, Jeng-Hun; Park, Seung Chul; Oh, Soojung; Jordan, Luke R.; Wittenberg, Nathan J.; Oh, Sang-Hyun; Jeon, Noo Li; Lee, Byoungho; Parikh, Atul N.; Lee, Sin-Doo

    2014-01-01

    During vesicular trafficking and release of enveloped viruses, the budding and fission processes dynamically remodel the donor cell membrane in a protein- or a lipid-mediated manner. In all cases, in addition to the generation or relief of the curvature stress, the buds recruit specific lipids and proteins from the donor membrane through restricted diffusion for the development of a ring-type raft domain of closed topology. Here, by reconstituting the bud topography in a model membrane, we demonstrate the preferential localization of cholesterol- and sphingomyelin-enriched microdomains in the collar band of the bud-neck interfaced with the donor membrane. The geometrical approach to the recapitulation of the dynamic membrane reorganization, resulting from the local radii of curvatures from nanometre-to-micrometre scales, offers important clues for understanding the active roles of the bud topography in the sorting and migration machinery of key signalling proteins involved in membrane budding. PMID:25058275

  12. Reconstituting ring-rafts in bud-mimicking topography of model membranes.

    PubMed

    Ryu, Yong-Sang; Lee, In-Ho; Suh, Jeng-Hun; Park, Seung Chul; Oh, Soojung; Jordan, Luke R; Wittenberg, Nathan J; Oh, Sang-Hyun; Jeon, Noo Li; Lee, Byoungho; Parikh, Atul N; Lee, Sin-Doo

    2014-01-01

    During vesicular trafficking and release of enveloped viruses, the budding and fission processes dynamically remodel the donor cell membrane in a protein- or a lipid-mediated manner. In all cases, in addition to the generation or relief of the curvature stress, the buds recruit specific lipids and proteins from the donor membrane through restricted diffusion for the development of a ring-type raft domain of closed topology. Here, by reconstituting the bud topography in a model membrane, we demonstrate the preferential localization of cholesterol- and sphingomyelin-enriched microdomains in the collar band of the bud-neck interfaced with the donor membrane. The geometrical approach to the recapitulation of the dynamic membrane reorganization, resulting from the local radii of curvatures from nanometre-to-micrometre scales, offers important clues for understanding the active roles of the bud topography in the sorting and migration machinery of key signalling proteins involved in membrane budding. PMID:25058275

  13. A mouse model mimicking human first night effect for the evaluation of hypnotics.

    PubMed

    Xu, Qi; Xu, Xin-Hong; Qu, Wei-Min; Lazarus, Michael; Urade, Yoshihiro; Huang, Zhi-Li

    2014-01-01

    In humans, a first night effect (FNE) is characterized by increased sleep latency and decreased total sleep time in an unfamiliar environment, but the mechanism and treatment options for this universally experienced acute insomnia are unclear. We continuously recorded electroencephalography (EEG) and electromyogram (EMG) and measured plasma corticosterone levels to develop a mouse FNE model by inducing acute insomnia in mice that have been placed in unfamiliar cage environments. The sleep latency of mice 'moved to clean cages' (MCC) was longer than that for mice 'moved to dirty ones' (MDC). As compared to MDC mice, MCC mice showed stronger decreases in the amount of non-rapid eye movement (non-REM, NREM) and REM sleep, with a lower power density of NREM sleep, increased fragmentation and decreased stage transitions from NREM sleep to wake, and higher variation in plasma corticosterone levels. Treatment of MCC mice with zolpidem, diazepam, raclopride, pyrilamine, except SCH23390 shortened NREM sleep latency. In addition, zolpidem significantly increased NREM and REM sleep with the increase in slow wave activity (1.00-2.75 Hz), while raclopride significantly increased NREM and REM sleep without changing the EEG power density in MCC mice, whereas diazepam increased sleep with a drastic decrease in power density of the frequency band between 1.00 and 4.00 Hz, diazepam also increased the frequency band between 9.75 and 24.75 Hz during NREM sleep. These results indicate that a MCC mouse can mimic a FNE phenotype of humans and that zolpidem and raclopride may be useful drugs to prevent acute insomnia, including FNE. PMID:24316349

  14. Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon

    PubMed Central

    Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C.; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

    2015-01-01

    In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor’s fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source. PMID:26559530

  15. Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

    PubMed Central

    Weidensdorfer, Marko; Chae, Ju Ik; Makobe, Celestine; Stahl, Julia; Averhoff, Beate; Müller, Volker; Schürmann, Christoph; Brandes, Ralf P.; Wilharm, Gottfried; Ballhorn, Wibke; Christ, Sara; Linke, Dirk; Fischer, Doris; Göttig, Stephan

    2015-01-01

    Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples (“organ microbiology”) might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially. PMID:26712205

  16. Macrophage infection models for Mycobacterium tuberculosis.

    PubMed

    Johnson, Benjamin K; Abramovitch, Robert B

    2015-01-01

    Mycobacterium tuberculosis colonizes, survives, and grows inside macrophages. In vitro macrophage infection models, using both primary macrophages and cell lines, enable the characterization of the pathogen response to macrophage immune pressure and intracellular environmental cues. We describe methods to propagate and infect primary murine bone marrow-derived macrophages and J774 and THP-1 macrophage-like cell lines. We also present methods on the characterization of M. tuberculosis intracellular survival and the preparation of infected macrophages for imaging. PMID:25779326

  17. From in vitro to in vivo Models of Bacterial Biofilm-Related Infections

    PubMed Central

    Lebeaux, David; Chauhan, Ashwini; Rendueles, Olaya; Beloin, Christophe

    2013-01-01

    The influence of microorganisms growing as sessile communities in a large number of human infections has been extensively studied and recognized for 30–40 years, therefore warranting intense scientific and medical research. Nonetheless, mimicking the biofilm-life style of bacteria and biofilm-related infections has been an arduous task. Models used to study biofilms range from simple in vitro to complex in vivo models of tissues or device-related infections. These different models have progressively contributed to the current knowledge of biofilm physiology within the host context. While far from a complete understanding of the multiple elements controlling the dynamic interactions between the host and biofilms, we are nowadays witnessing the emergence of promising preventive or curative strategies to fight biofilm-related infections. This review undertakes a comprehensive analysis of the literature from a historic perspective commenting on the contribution of the different models and discussing future venues and new approaches that can be merged with more traditional techniques in order to model biofilm-infections and efficiently fight them. PMID:25437038

  18. Animal Models of Mycobacteria Infection

    PubMed Central

    Ordway, Diane J.; Orme, Ian M.

    2011-01-01

    This unit describes the infection of mice and guinea pigs with mycobacteria via various routes, as well as necropsy methods for the determination of mycobacterial loads within target organs. Additionally, methods for cultivating mycobacteria and preparing stocks are described. The protocols outlined are primarily used for M. tuberculosis, but can also be used for the study of other non-tuberculosis mycobacterial species. PMID:18432756

  19. Zebrafish Embryo Model of Bartonella henselae Infection

    PubMed Central

    Lima, Amorce; Cha, Byeong J.; Amin, Jahanshah; Smith, Lisa K.

    2014-01-01

    Abstract Bartonella henselae (Bh) is an emerging zoonotic pathogen that has been associated with a variety of human diseases, including bacillary angiomatosis that is characterized by vasoproliferative tumor-like lesions on the skin of some immunosuppressed individuals. The study of Bh pathogenesis has been limited to in vitro cell culture systems due to the lack of an animal model. Therefore, we wanted to investigate whether the zebrafish embryo could be used to model human infection with Bh. Our data showed that Tg(fli1:egfp)y1 zebrafish embryos supported a sustained Bh infection for 7 days with >10-fold bacterial replication when inoculated in the yolk sac. We showed that Bh recruited phagocytes to the site of infection in the Tg(mpx:GFP)uwm1 embryos. Infected embryos showed evidence of a Bh-induced angiogenic phenotype and an increase in the expression of genes encoding pro-inflammatory factors and pro-angiogenic markers. However, infection of zebrafish embryos with a deletion mutant in the major adhesin (BadA) resulted in little or no bacterial replication and a diminished host response, providing the first evidence that BadA is critical for in vivo infection. Thus, the zebrafish embryo provides the first practical model of Bh infection that will facilitate efforts to identify virulence factors and define molecular mechanisms of Bh pathogenesis. PMID:25026365

  20. Experimental Validation of ARFI Surveillance of Subcutaneous Hemorrhage (ASSH) Using Calibrated Infusions in a Tissue-Mimicking Model and Dogs.

    PubMed

    Geist, Rebecca E; DuBois, Chase H; Nichols, Timothy C; Caughey, Melissa C; Merricks, Elizabeth P; Raymer, Robin; Gallippi, Caterina M

    2016-09-01

    Acoustic radiation force impulse (ARFI) Surveillance of Subcutaneous Hemorrhage (ASSH) has been previously demonstrated to differentiate bleeding phenotype and responses to therapy in dogs and humans, but to date, the method has lacked experimental validation. This work explores experimental validation of ASSH in a poroelastic tissue-mimic and in vivo in dogs. The experimental design exploits calibrated flow rates and infusion durations of evaporated milk in tofu or heparinized autologous blood in dogs. The validation approach enables controlled comparisons of ASSH-derived bleeding rate (BR) and time to hemostasis (TTH) metrics. In tissue-mimicking experiments, halving the calibrated flow rate yielded ASSH-derived BRs that decreased by 44% to 48%. Furthermore, for calibrated flow durations of 5.0 minutes and 7.0 minutes, average ASSH-derived TTH was 5.2 minutes and 7.0 minutes, respectively, with ASSH predicting the correct TTH in 78% of trials. In dogs undergoing calibrated autologous blood infusion, ASSH measured a 3-minute increase in TTH, corresponding to the same increase in the calibrated flow duration. For a measured 5% decrease in autologous infusion flow rate, ASSH detected a 7% decrease in BR. These tissue-mimicking and in vivo preclinical experimental validation studies suggest the ASSH BR and TTH measures reflect bleeding dynamics. PMID:26614530

  1. Melorheostosis mimicking synovial osteochondromatosis.

    PubMed

    Wadhwa, Vibhor; Chhabra, Avneesh; Samet, Jonathan D

    2014-01-01

    Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings. PMID:25971832

  2. Spatiotemporal modelling of viral infection dynamics

    NASA Astrophysics Data System (ADS)

    Beauchemin, Catherine

    Viral kinetics have been studied extensively in the past through the use of ordinary differential equations describing the time evolution of the diseased state in a spatially well-mixed medium. However, emerging spatial structures such as localized populations of dead cells might affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In the first phase of the project, a simple two-dimensional cellular automaton model of viral infections was developed. It was validated against clinical immunological data for uncomplicated influenza A infections and shown to be accurate enough to adequately model them. In the second phase of the project, the simple two-dimensional cellular automaton model was used to investigate the effects of relaxing the well-mixed assumption on viral infection dynamics. It was shown that grouping the initially infected cells into patches rather than distributing them uniformly on the grid reduced the infection rate as only cells on the perimeter of the patch have healthy neighbours to infect. Use of a local epithelial cell regeneration rule where dead cells are replaced by healthy cells when an immediate neighbour divides was found to result in more extensive damage of the epithelium and yielded a better fit to experimental influenza A infection data than a global regeneration rule based on division rate of healthy cell. Finally, the addition of immune cell at the site of infection was found to be a better strategy at low infection levels, while addition at random locations on the grid was the better strategy at high infection level. In the last project, the movement of T cells within lymph nodes in the absence of antigen, was investigated. Based on individual T cell track data captured by two-photon microscopy experiments in vivo, a simple model was proposed for the motion of T cells. This is the first step towards the implementation of a more realistic spatiotemporal model of HIV than

  3. A murine model of urinary tract infection

    PubMed Central

    Hung, Chia-Suei; Dodson, Karen W; Hultgren, Scott J

    2010-01-01

    Urinary tract infections (UTIs) inflict extreme pain and discomfort to those affected and have profound medical and socioeconomic impact. Although acute UTIs are often treatable with antibiotics, a large proportion of patients suffer from multiple recurrent infections. Here, we describe and provide a protocol for a robust murine UTI model that allows for the study of uropathogens in an ideal setting. The infections in the urinary tract can be monitored quantitatively by determining the bacterial loads at different times post-infection. In addition, the simple bladder architecture allows observation of disease progression and the uropathogenic virulence cascade using a variety of microscopic techniques. This mouse UTI model is extremely flexible, allowing the study of different bacterial strains and species of uropathogens in a broad range of mouse genetic backgrounds. We have used this protocol to identify important aspects of the host-pathogen interaction that determine the outcome of infection. The time required to complete the entire procedure will depend on the number of bacterial strains and mice included in the study. Nevertheless, one should expect 4 h of hands-on time, including inoculum preparation on the day of infection, transurethral inoculation, tissue harvest and post-harvest processing for a small group of mice (e.g., 5 mice). PMID:19644462

  4. Citrobacter rodentium mouse model of bacterial infection.

    PubMed

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete. PMID:27606775

  5. Mouse model for sublethal Leptospira interrogans infection.

    PubMed

    Richer, Luciana; Potula, Hari-Hara; Melo, Rita; Vieira, Ana; Gomes-Solecki, Maria

    2015-12-01

    Although Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4(+) and double-negative T cells (not CD8(+) cells) and that CD4(+) T cells acquired a CD44(high) CD62L(low) effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection). PMID:26416909

  6. Mouse Model for Sublethal Leptospira interrogans Infection

    PubMed Central

    Richer, Luciana; Potula, Hari-Hara; Melo, Rita; Vieira, Ana

    2015-01-01

    Although Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4+ and double-negative T cells (not CD8+ cells) and that CD4+ T cells acquired a CD44high CD62Llow effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection). PMID:26416909

  7. An animal model of human cytomegalovirus infection.

    PubMed

    Gao, L; Qian, S; Zeng, L; Wang, R; Wei, G; Fan, J; Zheng, S

    2007-12-01

    To develop a rat model that allowed in vivo progressive human cytomegalovirus (HCMV) infection, allogeneic liver transplantation was performed across a rat combination of Dark Agouti (DA) to Brown Norway (BN). AD169, a well-characterized laboratory strain of HCMV, was used to establish a rat model of HCMV infection by injection of 0.4 mL (30.0 logTCID50) supernate into the rat peritoneum. Histological and blood specimens were obtained from animals sacrificed at predetermined timepoints. We performed immunohistochemical staining in liver, heart, kidney, spleen, and lung for HCMV immediate-early antigen (IE), lower matrix protein (pp65) detection in peripheral blood leukocytes, and HCMV early antigen (EA) and late antigen (LA). We compared survival rates. Our results showed positive HCMV IE and pp65 antigenemia detected in peripheral blood leukocytes in transplanted recipients from day 1 to day 30. Positive HCMV EA and LA staining cells were only detected in sections 10 days after liver transplantation, namely, in hepatocytes, mononuclear cells, bile duct epithelial cells, and endothelial cells. Successful HCMV replication was due to the combination of liver transplantation and cyclosporine (CsA) immunosuppression. Survival analysis showed no significant differences between the HCMV-infected group and HCMV-uninfected group. This new rat model of HCMV infection may be helpful to understand immune system modulation of HCMV infection. PMID:18089401

  8. Kinetic model of HIV infection

    SciTech Connect

    Zhdanov, V. P.

    2007-10-15

    Recent experiments clarifying the details of exhaustion of CD8 T cells specific to various strains of human immunodeficiency virus (HIV) are indicative of slow irreversible (on a one-year time scale) deterioration of the immune system. The conventional models of HIV kinetics do not take this effect into account. Removing this shortcoming, we show the likely influence of such changes on the escape of HIV from control of the immune system.

  9. Modelling respiratory infection control measure effects

    PubMed Central

    LIAO, C. M.; CHEN, S. C.; CHANG, C. F.

    2008-01-01

    SUMMARY One of the most pressing issues in facing emerging and re-emerging respiratory infections is how to bring them under control with current public health measures. Approaches such as the Wells–Riley equation, competing-risks model, and Von Foerster equation are used to prioritize control-measure efforts. Here we formulate how to integrate those three different types of functional relationship to construct easy-to-use and easy-to-interpret critical-control lines that help determine optimally the intervention strategies for containing airborne infections. We show that a combination of assigned effective public health interventions and enhanced engineering control measures would have a high probability for containing airborne infection. We suggest that integrated analysis to enhance modelling the impact of potential control measures against airborne infections presents an opportunity to assess risks and benefits. We demonstrate the approach with examples of optimal control measures to prioritize respiratory infections of severe acute respiratory syndrome (SARS), influenza, measles, and chickenpox. PMID:17475088

  10. The effect of sediment mimicking drill cuttings on deep water rhodoliths in a flow-through system: Experimental work and modeling.

    PubMed

    Figueiredo, Marcia A O; Eide, Ingvar; Reynier, Marcia; Villas-Bôas, Alexandre B; Tâmega, Frederico T S; Ferreira, Carlos Gustavo; Nilssen, Ingunn; Coutinho, Ricardo; Johnsen, Ståle

    2015-06-15

    The impact of sediment coverage on two rhodolith-forming calcareous algae species collected at 100m water depth off the coast of Brazil was studied in an experimental flow-through system. Natural sediment mimicking drill cuttings with respect to size distribution was used. Sediment coverage and photosynthetic efficiency (maximum quantum yield of charge separation in photosystem II, ϕPSIImax) were measured as functions of light intensity, flow rate and added amount of sediment once a week for nine weeks. Statistical experimental design and multivariate data analysis provided statistically significant regression models which subsequently were used to establish exposure-response relationship for photosynthetic efficiency as function of sediment coverage. For example, at 70% sediment coverage the photosynthetic efficiency was reduced 50% after 1-2weeks of exposure, most likely due to reduced gas exchange. The exposure-response relationship can be used to establish threshold levels and impact categories for environmental monitoring. PMID:25935812

  11. Nonlinear hierarchical modeling of experimental infection data.

    PubMed

    Singleton, Michael D; Breheny, Patrick J

    2016-08-01

    In this paper, we propose a nonlinear hierarchical model (NLHM) for analyzing longitudinal experimental infection (EI) data. The NLHM offers several improvements over commonly used alternatives such as repeated measures analysis of variance (RM-ANOVA) and the linear mixed model (LMM). It enables comparison of relevant biological properties of the course of infection including peak intensity, duration and time to peak, rather than simply comparing mean responses at each observation time. We illustrate the practical benefits of this model and the insights it yields using data from experimental infection studies on equine arteritis virus. Finally, we demonstrate via simulation studies that the NLHM substantially reduces bias and improves the power to detect differences in relevant features of the infection response between two populations. For example, to detect a 20% difference in response duration between two groups (n=15) in which the peak time and peak intensity were identical, the RM-ANOVA test had a power of just 11%, and LMM a power of just 12%. By comparison, the nonlinear model we propose had a power of 58% in the same scenario, while controlling the Type I error rate better than the other two methods. PMID:27435656

  12. Swine model of Haemophilus ducreyi infection.

    PubMed Central

    Hobbs, M M; San Mateo, L R; Orndorff, P E; Almond, G; Kawula, T H

    1995-01-01

    Haemophilus ducreyi is a strict human pathogen that causes sexually transmitted genital ulcer disease. We infected domestic swine with H. ducreyi 35000, resulting in the development of cutaneous ulcers histologically resembling human chancroid lesions. Intraepidermal lesions progressed from pustules to ulcers containing polymorphonuclear leukocytes and were accompanied by a dermal inflammatory infiltrate containing T cells and macrophages. H. ducreyi was recovered from lesions up to 17 days after inoculation, and pigs did not develop immunity to reinfection with the challenge strain. Features of the model include inoculation through abrasions in the epidermis, ambient housing temperatures for infected pigs, the ability to deliver multiple different inocula to a single host, and the availability of monoclonal antibodies against porcine immune cells permitting immunohistochemical characterization of the host immune response to H. ducreyi infection. PMID:7622236

  13. An unusual case of vancomycin-related systemic reaction accompanied with severe thrombocytopenia mimicking pacemaker-related infective endocarditis: a case report and review of literature.

    PubMed

    Candemir, Basar; Aribuca, Aynur; Koca, Cigdem; Ozcan, Ozgur Ulas; Gerede, Menekse; Kaya, Cansin T

    2013-11-01

    Vancomycin is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive resistant bacteria. In recent years, several cases of vancomycin-associated immune thrombocytopenia have been presented as case reports, but the real incidence of this side effect is still unknown. In this report, we would like to present a case during which we confronted with a great dilemma: urgent removal of whole defibrillator system due to highly suspected infective endocarditis or leaving the defibrillator in place and simply switching vancomycin to another antibiotic agent and wait. PMID:23080329

  14. Geometric and electronic structures of the synthetic Mn4CaO4 model compound mimicking the photosynthetic oxygen-evolving complex.

    PubMed

    Shoji, Mitsuo; Isobe, Hiroshi; Shen, Jian-Ren; Yamaguchi, Kizashi

    2016-04-20

    Water oxidation by photosystem II (PSII) converts light energy into chemical energy with the concomitant production of molecular oxygen, both of which are indispensable for sustaining life on Earth. This reaction is catalyzed by an oxygen-evolving complex (OEC) embedded in the huge PSII complex, and its mechanism remains elusive in spite of the extensive studies of the geometric and electronic structures. In order to elucidate the water-splitting mechanism, synthetic approaches have been extensively employed to mimic the native OEC. Very recently, a synthetic complex [Mn4CaO4(Bu(t)COO)8(py)(Bu(t)COOH)2] () closely mimicking the structure of the native OEC was obtained. In this study, we extensively examined the geometric, electronic and spin structures of using the density functional theory method. Our results showed that the geometric structure of can be accurately reproduced by theoretical calculations, and revealed many similarities in the ground valence and spin states between and the native OEC. We also revealed two different valence states in the one-electron oxidized state of (corresponding to the S2 state), which lie in the lower and higher ground spin states (S = 1/2 and S = 5/2), respectively. One remarkable difference between and the native OEC is the presence of a non-negligible antiferromagnetic interaction between the Mn1 and Mn4 sites, which slightly influenced their ground spin structures (spin alignments). The major reason causing the difference can be attributed to the short Mn1-O5 and Mn1-Mn4 distances in . The introduction of the missing O4 atom and the reorientation of the Ca coordinating ligands improved the Mn1-O5 and Mn1-Mn4 distances comparable to the native OEC. These modifications will therefore be important for the synthesis of further advanced model complexes more closely mimicking the native OEC beyond . PMID:27055567

  15. Ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an HIV-infected patient.

    PubMed

    Bhat, Ramesh; Pinto, Malcolm; Dandakeri, Sukumar; Kambil, Srinath

    2013-12-01

    Leprosy maybe "unmasked" in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for Hansen's disease, need to be cognizant to this possibility. It may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration. PMID:24216029

  16. Modeling human influenza infection in the laboratory

    PubMed Central

    Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

    2015-01-01

    Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

  17. Animal model of Mycoplasma fermentans respiratory infection

    PubMed Central

    2013-01-01

    Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F) of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain), Mycoplasma fermentans PG 18 (type strain) or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans. PMID:23298636

  18. Animal models of human microsporidial infections.

    PubMed

    Snowden, K F; Didier, E S; Orenstein, J M; Shadduck, J A

    1998-12-01

    Two new models have been described for Enterocytozoon bieneusi, non-human primates and immuno-suppressed gnotobiotic pigs, but there still is no successful cell culture system. The intestinal xenograft system holds promise as an animal model for Encephalitozoon intestinalis. Encephalitozoon hellem is easily propagated in mice, and also may be an important cause of spontaneous disease of psittacine birds. Encephalitozoon cuniculi occurs spontaneously in a wide variety of animals and can be induced experimentally in athymic mice. This is a useful experimental system and animal model, but the infection is relatively rare in man. Mammalian microsporidioses first were recognized as spontaneous diseases of animals that later confounded studies intended to elucidate the nature of diseases of humans. Much was learned about both experimental and spontaneous animal microsporidial infections that subsequently has been applied to the human diseases. In addition, new diseases have appeared, in both animals and humans, for which models are being developed. Since there are now animal models for almost all the known human microsporidioses, information on pathogenesis, host defenses, and effective treatments may become available soon. The microsporidioses provide a good example of the value of comparative pathology. Dr. Payne: Joe Payne. How much accidental infection has occurred with adjacent laboratory animals? Dr. Shadduck: A hard question. The organisms are thought to spread horizontally, and there is some pretty good evidence for that in rabbits. One assumes that this also is the explanation for the occurrence in infected kennels. Horizontal transmission probably occurs via contaminated urine, at least in the case of rabbits and dogs. Experimentally, horizontal transmission has been difficult to demonstrate in mice. Relative to the danger in people, I don't know how to answer that. I have always treated this as one of those things where you should be careful, but you shouldn

  19. Infectivity model verification studies, annual report - 1981

    SciTech Connect

    McGrath, J.J.

    1982-01-01

    The infectivity model has been used as one of the leading indicators of the potential health effects that may be associated with energy-related pollutants including nitrogen dioxide (NOs), ozone, and diesel exhaust. The original studies with the infectivity model and chronic exposure to NO2 reported by Ehrlich and Henry (1968) have not been replicated. This report details the work that has been performed in Texas Tech's laboratory thus far in initiating a chronic NO2 exposure study to replicate the original work by Ehrlich and Henry, and reviews the preliminary results. At the end of the first contract year, a functioning inhalation facility with a capability to expose animals continuously to low levels of NO2 is in place. One group of animals has been exposed to NO2 for eight months and challenged with Klebsiella pneumonia by inhalation. The results are similar to, but do not replicate entirely, those reported by Ehrlich and Henry. Two additional exposures have been initiated, and the animals will be challenged with the infectious agent in a bacterial infectivity chamber similar to that used by EPA.

  20. Simple animal model of Helicobacter pylori infection

    PubMed Central

    Werawatganon, Duangporn

    2014-01-01

    Helicobacter pylori (H. pylori) has become accepted as a human pathogen for the development of gastritis and gastroduodenal ulcer. To develop a simple rat model of chronic H. pylori infection, male Sprague-Dawley rats were pretreated with streptomycin suspended in tap water (5 mg/mL) for 3 d. The rats were inoculated by gavage at 1 mL/rat with H. pylori suspension (5 × 108-5 × 1010 CFU/mL) twice daily at an interval of 4 h for three consecutive days. Two weeks after inoculation, rats were sacrificed and the stomachs were removed. Antral biopsies were performed for urease test and the stomachs were taken for histopathology. Successful H. pylori inoculation was defined as a positive urease test and histopathology. We reported a 69.8%-83.0% success rate for H. pylori infection using the urease test, and hematoxylin and eosin staining confirmed the results. Histopathological analysis detected bacteria along the mucous lining of the surface epithelium and crypt lumen and demonstrated mild to moderate gastric inflammation in successfully inoculated rats. We developed a simple rat model of chronic H. pylori infection for research into gastric microcirculatory changes and therapy with plant products. PMID:24914363

  1. Kaposi's sarcoma of the hand mimicking squamous cell carcinoma in a woman with no evidence of HIV infection: a case report

    PubMed Central

    Kosmidis, Christophoros; Efthimiadis, Christopher; Anthimidis, Georgios; karayannopoulou, Georgia; Grigoriou, Marios; Vassiliadou, Kalliopi; Berovali, Eleni; Fachantidis, Panagiotis; Fahantidis, Epaminondas

    2008-01-01

    Introduction Kaposi's sarcoma is a vascular neoplasm mainly affecting the skin of the lower extremities. Although it is the most common neoplasm affecting patients with AIDS, sporadic cases in HIV-negative people have been reported. It is a lesion mainly affecting men and its clinical presentation presents a challenge, as it can resemble other benign or malignant skin lesions. Case presentation We report a rare case of Kaposi's sarcoma presenting in a 68-year-old Mediterranean woman with no evidence of HIV infection. The patient had a 6-month history of a slowly progressing pigmented lesion on the dorsum of her left hand. The lesion clinically resembled a squamous cell carcinoma. The patient was treated with a wide excision of the lesion and primary reconstruction with a full thickness skin graft. Histopathological and immunohistochemical analysis of the excised lesion revealed the presence of Kaposi's sarcoma. Serologic investigation for HIV was negative but polymerase chain reaction for human herpes virus type 8 infection was positive. Thorough clinical and imaging investigation of the abdomen and chest were both negative for loci of disease. Conclusion Kaposi's sarcoma, although rare in its sporadic form, should be considered in the differential diagnosis of indeterminate skin lesions, especially those affecting the extremities. PMID:18565232

  2. A novel epidemic spreading model with decreasing infection rate based on infection times

    NASA Astrophysics Data System (ADS)

    Huang, Yunhan; Ding, Li; Feng, Yun

    2016-02-01

    A new epidemic spreading model where individuals can be infected repeatedly is proposed in this paper. The infection rate decreases according to the times it has been infected before. This phenomenon may be caused by immunity or heightened alertness of individuals. We introduce a new parameter called decay factor to evaluate the decrease of infection rate. Our model bridges the Susceptible-Infected-Susceptible(SIS) model and the Susceptible-Infected-Recovered(SIR) model by this parameter. The proposed model has been studied by Monte-Carlo numerical simulation. It is found that initial infection rate has greater impact on peak value comparing with decay factor. The effect of decay factor on final density and threshold of outbreak is dominant but weakens significantly when considering birth and death rates. Besides, simulation results show that the influence of birth and death rates on final density is non-monotonic in some circumstances.

  3. A mouse model of Salmonella typhi infection

    PubMed Central

    Mathur, Ramkumar; Oh, Hyunju; Zhang, Dekai; Park, Sung-Gyoo; Seo, Jin; Koblansky, Alicia; Hayden, Matthew S.; Ghosh, Sankar

    2012-01-01

    Salmonella spp. are gram-negative flagellated bacteria that can cause food and water-borne gastroenteritis and typhoid fever in humans. We now report that flagellin from Salmonella spp. is recognized in mouse intestine by Toll-like receptor 11 (TLR11). Absence of TLR11 renders mice more susceptible to infection by S. typhimurium, with increased dissemination of the bacteria and enhanced lethality. Unlike S. typhimurium, S. typhi, a human obligatory pathogen that causes typhoid fever, is normally unable to infect mice. TLR11 is expressed in mice but not in humans, and remarkably, we find that tlr11−/− mice are efficiently infected with orally-administered S. typhi. We also find that tlr11−/− mice can be immunized against S. typhi. Therefore, tlr11−/− mice represent the first small animal model for the study of the immune response to S. typhi, and for the development of vaccines against this important human pathogen. PMID:23101627

  4. Mouse infection models for space flight immunology

    NASA Technical Reports Server (NTRS)

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

    2005-01-01

    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  5. Strongyloides stercoralis: Amphidial neuron pair ASJ triggers significant resumption of development by infective larvae under host-mimicking in vitro conditions

    PubMed Central

    Ashton, Francis T.; Zhu, Xiaodong; Boston, Ray; Lok, James B.; Schad, Gerhard A.

    2011-01-01

    Resumption of development by infective larvae (L3i) of parasitic nematodes upon entering a host is a critical first step in establishing a parasitic relationship with a definitive host. It is also considered equivalent to exit from the dauer stage by the free-living nematode Caenorhabditis elegans. Initiation of feeding, an early event in this process, is induced in vitro in L3i of Strongyloides stercoralis, a parasite of humans, other primates and dogs, by culturing the larvae in DMEM with 10% canine serum and 5 mM glutathione at 37 °C with 5% CO2. Based on the developmental neurobiology of C. elegans, resumption of development by S. stercoralis L3i should be mediated, in part at least, by neurons homologous to the ASJ pair of C. elegans. To test this hypothesis, the ASJ neurons in S. stercoralis first-stage larvae (L1) were ablated with a laser microbeam. This resulted in a statistically significant (33%) reduction in the number of L3i that resumed feeding in culture. In a second expanded investigation, the thermosensitive ALD neurons, along with the ASJ neurons, were ablated, but there was no further decrease in the initiation of feeding by these worms compared to those in which only the ASJ pair was ablated. PMID:17067579

  6. Humanized Mouse Models of HIV Infection

    PubMed Central

    Denton, Paul W.; Garcia, J. Victor

    2013-01-01

    Because of the limited tropism of HIV, in vivo modeling of this virus has been almost exclusively limited to other lentiviruses such as SIV that reproduce many important characteristics of HIV infection. However, there are significant genetic and biological differences among lentiviruses and some HIV-specific interventions are not effective against other lentiviruses in non-human hosts. For these reasons much emphasis has recently been placed on developing alternative animal models that support HIV replication and recapitulate key aspects of HIV infection and pathogenesis in humans. Humanized mice, CD34+ hematopoietic progenitor cell transplanted immunodeficient mice and in particular mice also implanted with human thymic/liver tissue (BLT mice) that develop a functional human immune system, have been the focus of a great deal of attention as possible models to study virtually all aspects of HIV biology and pathogenesis. Humanized mice are systemically reconstituted with human lymphoid cells offering rapid, reliable and reproducible experimental systems for HIV research. Peripheral blood of humanized mice can be readily sampled longitudinally to assess reconstitution with human cells and to monitor HIV replication permitting the evaluation of multiple parameters of HIV infection such as viral load levels, CD4+ T cell depletion, immune activation, as well as the effects of therapeutic interventions. Of high relevance to HIV transmission is the extensive characterization and validation of the reconstitution with human lymphoid cells of the female reproductive tract and of the gastrointestinal tract of humanized BLT mice that renders them susceptible to both vaginal and rectal HIV infection. Other important attributes of all types of humanized mice include: 1) their small size and cost that make them broadly accessible; 2) multiple cohorts of humanized mice can be made from multiple human donors and each cohort has identical human cells, permitting control of

  7. In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.

    PubMed

    Andreoni, Chiara; Orsi, Gianni; De Maria, Carmelo; Montemurro, Francesca; Vozzi, Giovanni

    2014-01-01

    The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis. PMID:25502576

  8. In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle

    PubMed Central

    Andreoni, Chiara; Orsi, Gianni; De Maria, Carmelo; Montemurro, Francesca; Vozzi, Giovanni

    2014-01-01

    The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis. PMID:25502576

  9. Postoperative fungal arteritis mimicking vasospasm--case report.

    PubMed

    Piotrowski, W P; Pilz, P

    1994-05-01

    Intracranial arteritis due to fungal infection is an uncommon complication of neurosurgical operations. A 36-year-old female developed arteritis caused by Aspergillus fumigatus at the site of the temporary clip following the clipping of an initially uncomplicated intracranial aneurysm. The inflammatory, slowly progressing vascular occlusion mimicked the vasospasm common in subarachnoid hemorrhage. PMID:7519756

  10. A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep

    PubMed Central

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Background Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Methodology/Principal Findings Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>104 cfu/g). Conclusions/Significance The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. PMID:23874438

  11. Henipavirus infections: lessons from animal models.

    PubMed

    Dhondt, Kévin P; Horvat, Branka

    2013-01-01

    The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed. PMID:25437037

  12. Longitudinal Analysis of Osteogenic and Angiogenic Signaling Factors in Healing Models Mimicking Atrophic and Hypertrophic Non-Unions in Rats

    PubMed Central

    Minkwitz, Susann; Faßbender, Mirja; Kronbach, Zienab; Wildemann, Britt

    2015-01-01

    Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group) to an open osteotomy (hypertrophy group) led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group) decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing. PMID:25910190

  13. Primary ovarian and pararectal hydatid cysts mimicking pelvic endometriosis.

    PubMed

    Bozkurt, Murat; Bozkurt, Duygu Kara; Çil, Ahmet Said; Karaman, Mehmet

    2012-01-01

    We report a case of 48-year-old woman with multiple hydatid cysts in pararectal region and right paraovarian localization with an unusual sonographic and computed tomographic presentation mimicking a pelvic endometriosis. During laparotomy, multiple pararectal and right ovarian cysts resembling endometriosis were resected. Pathologic examination gives the diagnosis of hydatid cysts. Retrospectively, we investigate the primary infection but the patient had no history of hepatic and liver involvement, it is a case of primary infection. PMID:23456529

  14. A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes.

    PubMed

    Shelby, J Patrick; White, John; Ganesan, Karthikeyan; Rathod, Pradipsinh K; Chiu, Daniel T

    2003-12-01

    Severe malaria by Plasmodium falciparum is a potentially fatal disease, frequently unresponsive to even the most aggressive treatments. Host organ failure is associated with acquired rigidity of infected red blood cells and capillary blockage. In vitro techniques have played an important role in modeling cell deformability. Although, historically they have either been applied to bulk cell populations or to measure single physical parameters of individual cells. In this article, we demonstrate the unique abilities and benefits of elastomeric microchannels to characterize complex behaviors of single cells, under flow, in multicellular capillary blockages. Channels of 8-, 6-, 4-, and 2-microm widths were readily traversed by the 8 microm-wide, highly elastic, uninfected red blood cells, as well as by infected cells in the early ring stages. Trophozoite stages failed to freely traverse 2- to 4-microm channels; some that passed through the 4-microm channels emerged from constricted space with deformations whose shape-recovery could be observed in real time. In 2-microm channels, trophozoites mimicked "pitting," a normal process in the body where spleen beds remove parasites without destroying the red cell. Schizont forms failed to traverse even 6-microm channels and rapidly formed a capillary blockage. Interestingly, individual uninfected red blood cells readily squeezed through the blockages formed by immobile schizonts in a 6-microm capillary. The last observation can explain the high parasitemia in a growing capillary blockage and the well known benefits of early blood transfusion in severe malaria. PMID:14638939

  15. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

    PubMed

    Song, Z; Johansen, H K; Moser, C; Høiby, N

    1996-05-01

    The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable. PMID:8703440

  16. Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

    NASA Astrophysics Data System (ADS)

    Damanik, Febriyani F. R.; Rothuizen, Tonia C.; van Blitterswijk, Clemens; Rotmans, Joris I.; Moroni, Lorenzo

    2014-09-01

    Despite various studies to minimize host reaction following a biomaterial implantation, an appealing strategy in regenerative medicine is to actively use such an immune response to trigger and control tissue regeneration. We have developed an in vitro model to modulate the host response by tuning biomaterials' surface properties through surface modifications techniques as a new strategy for tissue regeneration applications. Results showed tunable surface topography, roughness, wettability, and chemistry by varying treatment type and exposure, allowing for the first time to correlate the effect of these surface properties on cell attachment, morphology, strength and proliferation, as well as proinflammatory (IL-1β, IL-6) and antiflammatory cytokines (TGF-β1, IL-10) secreted in medium, and protein expression of collagen and elastin. Surface microstructuring, derived from chloroform partial etching, increased surface roughness and oxygen content. This resulted in enhanced cell adhesion, strength and proliferation as well as a balance of soluble factors for optimum collagen and elastin synthesis for tissue regeneration. By linking surface parameters to cell activity, we could determine the fate of the regenerated tissue to create successful soft tissue-engineered replacement.

  17. Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

    PubMed Central

    Damanik, Febriyani F. R.; Rothuizen, Tonia C.; van Blitterswijk, Clemens; Rotmans, Joris I.; Moroni, Lorenzo

    2014-01-01

    Despite various studies to minimize host reaction following a biomaterial implantation, an appealing strategy in regenerative medicine is to actively use such an immune response to trigger and control tissue regeneration. We have developed an in vitro model to modulate the host response by tuning biomaterials' surface properties through surface modifications techniques as a new strategy for tissue regeneration applications. Results showed tunable surface topography, roughness, wettability, and chemistry by varying treatment type and exposure, allowing for the first time to correlate the effect of these surface properties on cell attachment, morphology, strength and proliferation, as well as proinflammatory (IL-1β, IL-6) and antiflammatory cytokines (TGF-β1, IL-10) secreted in medium, and protein expression of collagen and elastin. Surface microstructuring, derived from chloroform partial etching, increased surface roughness and oxygen content. This resulted in enhanced cell adhesion, strength and proliferation as well as a balance of soluble factors for optimum collagen and elastin synthesis for tissue regeneration. By linking surface parameters to cell activity, we could determine the fate of the regenerated tissue to create successful soft tissue-engineered replacement. PMID:25234587

  18. Development and application of an oral challenge mouse model for studying Clostridium perfringens type D infection.

    PubMed

    Fernandez-Miyakawa, Mariano E; Sayeed, Sameera; Fisher, Derek J; Poon, Rachael; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Saputo, Julian; Uzal, Francisco A

    2007-09-01

    Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections. PMID:17562765

  19. Modeling multiple infection of cells by viruses: challenges and insights

    PubMed Central

    Phan, Dustin; Wodarz, Dominik

    2015-01-01

    The multiple infection of cells with several copies of a given virus has been demonstrated in experimental systems, and has been subject to previous mathematical modeling approaches. Such models, especially those based on ordinary differential equations, can be characterized by difficulties and pitfalls. One such difficulty arises from what we refer to as multiple infection cascades. That is, such models subdivide the infected cell population into sub-populations that are carry i viruses, and each sub-population can in principle always be further infected to contain i+1 viruses. In order to study the model with numerical simulations, the infection cascade needs to be cut artificially, and this can influence the results. This is shown here in the context of the simplest setting that involves a single, homogeneous virus population. If the viral replication rate is sufficiently fast, then most infected cells will accumulate in the last member of the infection cascade, leading to incorrect numerical results. This can be observed even with relatively long infection cascades, and in this case computational costs associated with a sufficiently long infection cascade can render this approach impractical. We subsequently examine a more complex scenario where two virus types / strains with different fitness are allowed to compete. Again, we find that the length of the infection cascade can have a crucial influence on the results. Competitive exclusion can be observed for shorter infection cascades, while coexistence can be observed for longer infection cascades. More subtly, the length of the infection cascade can influence the equilibrium level of the populations in numerical simulations. Studying the model in a parameter regime where an increase in the infection cascade length does not influence the results, we examine the effect of multiple infection on the outcome of competition. We find that multiple infection can promote coexistence of virus types if there is a degree

  20. Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

    PubMed Central

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-01-01

    Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream. PMID:24747976

  1. Lagenidium sp. Ocular Infection Mimicking Ocular Pythiosis

    PubMed Central

    Reinprayoon, Usanee; Permpalung, Nitipong; Plongla, Rongpong; Mendoza, Leonel; Chindamporn, Ariya

    2013-01-01

    This is a report of a Lagenidium sp. in a Thai patient who was diagnosed with severe keratitis that was unresponsive to antibacterial and antifungal drugs. Examination of a corneal biopsy specimen confirmed the presence of aseptate hyphae. The internal transcribed spacer DNA sequence of the strain isolated showed 97% identity with Lagenidium giganteum and other Lagenidium species. PMID:23740721

  2. Lagenidium sp. ocular infection mimicking ocular pythiosis.

    PubMed

    Reinprayoon, Usanee; Permpalung, Nitipong; Kasetsuwan, Ngamjit; Plongla, Rongpong; Mendoza, Leonel; Chindamporn, Ariya

    2013-08-01

    This is a report of a Lagenidium sp. in a Thai patient who was diagnosed with severe keratitis that was unresponsive to antibacterial and antifungal drugs. Examination of a corneal biopsy specimen confirmed the presence of aseptate hyphae. The internal transcribed spacer DNA sequence of the strain isolated showed 97% identity with Lagenidium giganteum and other Lagenidium species. PMID:23740721

  3. Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.

    PubMed

    Czechowicz, R T; Warren, L J; Moore, L; Saxon, B

    2001-02-01

    A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia developed a rapidly expanding red annular plaque on her thigh, initially without signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in the blood vessel walls. In immunocompromised individuals, skin biopsy and culture of cutaneous lesions for bacteria and fungi should be considered even in the absence of signs of systemic toxicity or multiple lesions. PMID:11233725

  4. A Rat Model of Central Venous Catheter to Study Establishment of Long-Term Bacterial Biofilm and Related Acute and Chronic Infections

    PubMed Central

    Chauhan, Ashwini; Lebeaux, David; Decante, Benoit; Kriegel, Irene; Escande, Marie-Christine; Ghigo, Jean-Marc; Beloin, Christophe

    2012-01-01

    Formation of resilient biofilms on medical devices colonized by pathogenic microorganisms is a major cause of health-care associated infection. While in vitro biofilm analyses led to promising anti-biofilm approaches, little is known about their translation to in vivo situations and on host contribution to the in vivo dynamics of infections on medical devices. Here we have developed an in vivo model of long-term bacterial biofilm infections in a pediatric totally implantable venous access port (TIVAP) surgically placed in adult rats. Using non-invasive and quantitative bioluminescence, we studied TIVAP contamination by clinically relevant pathogens, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, and we demonstrated that TIVAP bacterial populations display typical biofilm phenotypes. In our study, we showed that immunocompetent rats were able to control the colonization and clear the bloodstream infection except for up to 30% that suffered systemic infection and death whereas none of the immunosuppressed rats survived the infection. Besides, we mimicked some clinically relevant TIVAP associated complications such as port-pocket infection and hematogenous route of colonization. Finally, by assessing an optimized antibiotic lock therapy, we established that our in vivo model enables to assess innovative therapeutic strategies against bacterial biofilm infections. PMID:22615964

  5. Bacteriophage Infection of Model Metal Reducing Bacteria

    NASA Astrophysics Data System (ADS)

    Weber, K. A.; Bender, K. S.; Gandhi, K.; Coates, J. D.

    2008-12-01

    filtered through a 0.22 μ m sterile nylon filter, stained with phosphotungstic acid (PTA), and examined using transmission electron microscopy (TEM). TEM revealed the presence of viral like particles in the culture exposed to mytomycin C. Together these results suggest an active infection with a lysogenic bacteriophage in the model metal reducing bacteria, Geobacter spp., which could affect metabolic physiology and subsequently metal reduction in environmental systems.

  6. Modeling Zika Virus Infection in Pregnancy.

    PubMed

    Mysorekar, Indira U; Diamond, Michael S

    2016-08-01

    There were few studies of Zika virus (ZIKV), a flavivirus, until this past year, when large epidemics in the Americas were accompanied by unexpectedly severe clinical manifestations. Infection in pregnant women has emerged as a major global concern because of its linkage to congenital abnormalities including microcephaly, spontaneous abortion, and intrauterine growth restriction.(1) In addition, ZIKV infection in other age groups has been associated with severe neurologic disease and the Guillain-Barré syndrome.(2) Transmission cycles between humans and Aedes aegypti mosquitoes in urban settings can cause large-scale epidemics of ZIKV infection. Although mosquitoes clearly are the primary cause of ZIKV outbreaks, . . . PMID:27433842

  7. Dynamics of a Class of HIV Infection Models with Cure of Infected Cells in Eclipse Stage.

    PubMed

    Maziane, Mehdi; Lotfi, El Mehdi; Hattaf, Khalid; Yousfi, Noura

    2015-12-01

    In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations (ODEs) and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check our theoretical results with numerical simulations. PMID:26082312

  8. Endobronchial Tuberculosis Mimicking Asthma

    PubMed Central

    Argun Baris, Serap; Onyilmaz, Tuğba; Basyigit, Ilknur; Boyaci, Hasim

    2015-01-01

    Endobronchial tuberculosis (EBTB) is defined as tuberculosis infection of the tracheobronchial tree with microbial and histopathological evidence. The clinical symptoms of the diseases are nonspecific. Chronic cough is the major symptom of the disease. The diagnosis is often delayed due to its nonspecific presentation and misdiagnosed as bronchial asthma. This case is presented to recall the notion that the endobronchial tuberculosis can mimic asthma and the importance of bronchoscopic evaluation in a patient with chronic cough and treatment resistant asthma. PMID:26798513

  9. Enterococcus infection biology: lessons from invertebrate host models.

    PubMed

    Yuen, Grace J; Ausubel, Frederick M

    2014-03-01

    The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans. PMID:24585051

  10. Enterococcus Infection Biology: Lessons from Invertebrate Host Models

    PubMed Central

    Yuen, Grace J.; Ausubel, Frederick M.

    2015-01-01

    The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans. PMID:24585051

  11. Animal models of henipavirus infection: a review.

    PubMed

    Weingartl, Hana M; Berhane, Yohannes; Czub, Markus

    2009-09-01

    Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level four pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarises current published data relating to experimental infection of small and large animals, including the natural reservoir species, the Pteropus bat, with HeV or NiV. Susceptibility to infection and virus distribution in the individual species is discussed, along with the pathogenesis, pathological changes, and potential routes of transmission. PMID:19084436

  12. Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

    NASA Astrophysics Data System (ADS)

    Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

    2015-10-01

    Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

  13. Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

    PubMed Central

    Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

    2015-01-01

    Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. PMID:26482413

  14. A SIRS epidemic model with infection-age dependence

    NASA Astrophysics Data System (ADS)

    Zhang, Zhonghua; Peng, Jigen

    2007-07-01

    Based on J. Mena-Lorca and H.W. Hethcote's epidemic model, a SIRS epidemic model with infection-age-dependent infectivity and general nonlinear contact rate is formulated. Under general conditions, the unique existence of its global positive solutions is obtained. Moreover, under more general assumptions than the existing, the existence and asymptotical stability of its equilibria are discussed. In the end, the condition on the stability of endemic equilibrium is verified by a special model.

  15. Susceptibility to infection and pathogenicity of White Spot Disease (WSD) in non-model crustacean host taxa from temperate regions.

    PubMed

    Bateman, K S; Tew, I; French, C; Hicks, R J; Martin, P; Munro, J; Stentiford, G D

    2012-07-01

    Despite almost two decades since its discovery, White Spot Disease (WSD) caused by White Spot Syndrome Virus (WSSV) is still considered the most significant known pathogen impacting the sustainability and growth of the global penaeid shrimp farming industry. Although most commonly associated with penaeid shrimp farmed in tropical regions, the virus is also able to infect, cause disease and kill a wide range of other decapod crustacean hosts from temperate regions, including lobsters, crabs, crayfish and shrimp. For this reason, WSSV has recently been listed in European Community Council Directive 2006/88. Using principles laid down by the European Food Safety Authority (EFSA) we applied an array of diagnostic approaches to provide a definitive statement on the susceptibility to White Spot Syndrome Virus (WSSV) infection in seven ecologically or economically important crustacean species from Europe. We chose four marine species: Cancer pagurus, Homarus gammarus, Nephrops norvegicus and Carcinus maenas; one estuarine species, Eriocheir sinensis and two freshwater species, Austropotamobius pallipes and Pacifastacus leniusculus. Exposure trials based upon natural (feeding) and artificial (intra-muscular injection) routes of exposure to WSSV revealed universal susceptibility to WSSV infection in these hosts. However, the relative degree of susceptibility (measured by progression of infection to disease, and mortality) varied significantly between host species. In some instances (Type 1 hosts), pathogenesis mimicked that observed in penaeid shrimp hosts whereas in other examples (Types 2 and 3 hosts), infection did not readily progress to disease, even though hosts were considered as infected and susceptible according to accepted principles. Results arising from challenge studies are discussed in relation to the potential risk posed to non-target hosts by the inadvertent introduction of WSSV to European waters via trade. Furthermore, we highlight the potential for

  16. Modeling Influenza Virus Infection: A Roadmap for Influenza Research

    PubMed Central

    Boianelli, Alessandro; Nguyen, Van Kinh; Ebensen, Thomas; Schulze, Kai; Wilk, Esther; Sharma, Niharika; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Toapanta, Franklin R.; Guzmán, Carlos A.; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization. PMID:26473911

  17. Effects of distribution of infection rate on epidemic models

    NASA Astrophysics Data System (ADS)

    Lachiany, Menachem; Louzoun, Yoram

    2016-08-01

    A goal of many epidemic models is to compute the outcome of the epidemics from the observed infected early dynamics. However, often, the total number of infected individuals at the end of the epidemics is much lower than predicted from the early dynamics. This discrepancy is argued to result from human intervention or nonlinear dynamics not incorporated in standard models. We show that when variability in infection rates is included in standard susciptible-infected-susceptible (SIS ) and susceptible-infected-recovered (SIR ) models the total number of infected individuals in the late dynamics can be orders lower than predicted from the early dynamics. This discrepancy holds for SIS and SIR models, where the assumption that all individuals have the same sensitivity is eliminated. In contrast with network models, fixed partnerships are not assumed. We derive a moment closure scheme capturing the distribution of sensitivities. We find that the shape of the sensitivity distribution does not affect R0 or the number of infected individuals in the early phases of the epidemics. However, a wide distribution of sensitivities reduces the total number of removed individuals in the SIR model and the steady-state infected fraction in the SIS model. The difference between the early and late dynamics implies that in order to extrapolate the expected effect of the epidemics from the initial phase of the epidemics, the rate of change in the average infectivity should be computed. These results are supported by a comparison of the theoretical model to the Ebola epidemics and by numerical simulation.

  18. Effects of distribution of infection rate on epidemic models.

    PubMed

    Lachiany, Menachem; Louzoun, Yoram

    2016-08-01

    A goal of many epidemic models is to compute the outcome of the epidemics from the observed infected early dynamics. However, often, the total number of infected individuals at the end of the epidemics is much lower than predicted from the early dynamics. This discrepancy is argued to result from human intervention or nonlinear dynamics not incorporated in standard models. We show that when variability in infection rates is included in standard susciptible-infected-susceptible (SIS) and susceptible-infected-recovered (SIR) models the total number of infected individuals in the late dynamics can be orders lower than predicted from the early dynamics. This discrepancy holds for SIS and SIR models, where the assumption that all individuals have the same sensitivity is eliminated. In contrast with network models, fixed partnerships are not assumed. We derive a moment closure scheme capturing the distribution of sensitivities. We find that the shape of the sensitivity distribution does not affect R_{0} or the number of infected individuals in the early phases of the epidemics. However, a wide distribution of sensitivities reduces the total number of removed individuals in the SIR model and the steady-state infected fraction in the SIS model. The difference between the early and late dynamics implies that in order to extrapolate the expected effect of the epidemics from the initial phase of the epidemics, the rate of change in the average infectivity should be computed. These results are supported by a comparison of the theoretical model to the Ebola epidemics and by numerical simulation. PMID:27627337

  19. Bispecific antibody mimicking factor VIII.

    PubMed

    Nogami, Keiji

    2016-05-01

    There are some issues in the current factor (F)VIII replacement therapy for severe hemophilia A. One is mental and physical burden for the multiple intravenous infusions, and the other is difficulty in the hemostatic treatment for the patients with FVIII inhibitor. The development of novel drug with fully hemostatic effect, simply procedure, and long-acting reaction has been expected. Recently, FVIIIa-mimicking humanized recombinant bispecific antibody (ACE910) against FIXa and FX was developed. In the non-human clinical study, primate model of acquired hemophilia A demonstrated that the ACE910 was effective on both on-going and spontaneous bleedings. A phase I clinical study was conducted in healthy adults by single subcutaneous infusion of ACE910, followed by the patients' part study, Japanese patients with severe hemophilia A without or with inhibitor were treated with once-weekly subcutaneous injection of ACE910 at three dose levels for 12 successive weeks. There was no significant adverse event related to ACE910 in the clinical and laboratorial findings, and t1/2 of ACE910 was ∼30 days. The median annual bleeding rates were reduced very markedly dose-dependently, independently of inhibitor. Furthermore, among the patients with dose escalation, bleeding rate was decreased as ACE910 dose was increased. In conclusion, ACE910 would have a number of promising features: its high subcutaneous bioavailability and long half-life make the patients possible to be injected subcutaneously with a once-a-week or less frequency. In addition, ACE910 would provide the bleeding prophylactic efficacy, independently of inhibitor. PMID:27207420

  20. Xanthogranulomatous cholecystitis mimicking gallbladder cancer.

    PubMed

    Ewelukwa, Ofor; Ali, Omair; Akram, Salma

    2014-01-01

    Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer. PMID:24811556

  1. Xanthogranulomatous cholecystitis mimicking gallbladder cancer

    PubMed Central

    Ewelukwa, Ofor; Ali, Omair; Akram, Salma

    2014-01-01

    Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer. PMID:24811556

  2. Atypical Cogan's syndrome mimicking encephalitis.

    PubMed

    Lepur, Dragan; Vranjican, Zoran; Himbele, Josip; Barsić, Bruno; Klinar, Igor

    2004-01-01

    Cogan's syndrome is a rare autoimmune multisystem disease. The main clinical features of typical Cogan's syndrome are vestibuloauditory dysfunction and interstitial keratitis. The authors present a case of atypical Cogan's syndrome with headache, fever, deafness, trigeminal neuralgia and electroencephalographic abnormality which mimicked viral encephalitis. PMID:15307593

  3. Kawasaki Disease Mimicking Retropharyngeal Abscess

    PubMed Central

    Srividhya, Vazhkudai Sridharan; Vasanthi, Thiruvengadam; Shivbalan, Somu

    2010-01-01

    Kawasaki disease is an acute, self-limiting febrile mucocutaneous vasculitis of infants and young children. Retropharyngeal lymphadenopathy is a rare presentation of Kawasaki disease. We present a case of Kawasaki disease mimicking a retropharyngeal abscess, with upper airway obstruction resulting in delayed diagnosis. PMID:20635457

  4. Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila

    PubMed Central

    Pilloux, Ludovic; LeRoy, Didier; Brunel, Christophe

    2016-01-01

    Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium. PMID:26950066

  5. Tetraodon nigroviridis: A model of Vibrio parahaemolyticus infection.

    PubMed

    Peng, Wan; Shi, Yu; Li, Gao-Fei; He, Liang-Ge; Liang, Yao-Si; Zhang, Yong; Zhou, Li-Bin; Lin, Hao-Ran; Lu, Dan-Qi

    2016-09-01

    Vibriosis is the most common bacterial diseases and brings great economic loss on aquaculture. Vibrio parahaemolyticus (V. parahaemolyticus), a gram-negative bacterium, has been identified as one main pathogens of Vibriosis. The pathogenic mechanism of V. parahaemolyticus is not entirely clear now. In our study, a model of V. parahaemolyticus infection of green-spotted puffer fish (Tetraodon nigroviridis) was established. T. nigroviridis were injected intraperitoneally (i.p.) with 200 μL of V. parahaemolyticus (8 × 10(10) CFU/mL). V. parahaemolyticus infection caused 64% mortality and infected some organs of T. nigroviridis. Histopathology studies revealed V. parahaemolyticus infection induced tissue structural changes, including adipose hollow space in the liver. Immunohistochemistry showed V. parahaemolyticus were present in infected tissue such as liver, head kidney and spleen. In livers of T. nigroviridis infected by V. parahaemolyticus, the alkaline phosphatases (ALP) activity first gradually increased and then backed to normal level, a trend that was on the contrary to the expression profile of the miR-29b. Quantitative real-time PCR analysis showed that the expression level of TLR1, TLR2, TLR5, TLR9, TLR21, NOD1, NOD2 and IL-6 in response to V. parahaemolyticus infection decreased compared to that of non-infected fish. The establishment of the T. nigroviridis model of V. parahaemolyticus infection further confirmed V. parahaemolyticus spreads through the blood circulation system primary as an extracellular pathogen. Meanwhile, liver is an important target organ when infected by V. parahaemolyticus. miR-29b in liver was involved in the progress of liver steatosis during V. parahaemolyticus infection. Moreover, V. parahaemolyticus infection in vivo may have an effect of immunosuppression on host. PMID:27426523

  6. A mouse model of food borne Listeria monocytogenes infection

    PubMed Central

    Bou Ghanem, Elsa N.; Myers-Morales, Tanya

    2014-01-01

    Listeria monocytogenes cause foodborne disease in humans that ranges in severity from mild, self-limiting gastroenteritis to life-threatening systemic infections of the blood, brain, or placenta. The most commonly used animal model of listeriosis is intravenous infection of mice. This systemic model is highly reproducible, and thus, useful for studying cell-mediated immune responses against an intracellular bacterial pathogen, but it completely bypasses the gastrointestinal phase of L. monocytogenes infection. Intragastric inoculation of L. monocytogenes produces more variable results and may cause direct bloodstream invasion in some animals. The food borne transmission model described here does not require specialized skills to perform and results in infections that more closely mimic human disease. This natural feeding model can be used to study both the host and pathogen-derived factors that govern susceptibility or resistance to orally acquired L. monocytogenes. PMID:24510293

  7. Pineal toxoplasmosis mimicking pineal tumor in an AIDS patient.

    PubMed

    Poon, T P; Behbahani, M; Matoso, I; Kim, B

    1994-07-01

    A pineal mass in a patient with acquired immunodeficiency syndrome (AIDS) is reported. Computed tomography (CT) scan revealed a nodular mass in the pineal region with foci of calcification and obstruction of the aqueduct mimicking a pineal tumor. At autopsy, the brain revealed a well-circumscribed lesion with central necrosis in the pineal region suggestive of toxoplasma and involving the periaqueductal area. Susceptibility of a patient with AIDS to opportunistic infections should be considered. PMID:8064908

  8. Impacts of Humanized Mouse Models on the Investigation of HIV-1 Infection: Illuminating the Roles of Viral Accessory Proteins in Vivo

    PubMed Central

    Yamada, Eri; Yoshikawa, Rokusuke; Nakano, Yusuke; Misawa, Naoko; Koyanagi, Yoshio; Sato, Kei

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models. PMID:25807049

  9. Evaluating efficacy of bacteriophage therapy against Staphylococcus aureus infections using a silkworm larval infection model.

    PubMed

    Takemura-Uchiyama, Iyo; Uchiyama, Jumpei; Kato, Shin-ichiro; Inoue, Tetsuyoshi; Ujihara, Takako; Ohara, Naoya; Daibata, Masanori; Matsuzaki, Shigenobu

    2013-10-01

    Silkworm larva has recently been recognized as an alternative model animal for higher mammals to evaluate the effects of antibiotics. In this study, we examined the efficacy of the bacteriophage (phage) therapy, which harnesses phages as antibacterial agents, against Staphylococcus aureus infections, using the silkworm larval infection model. Two newly isolated staphylococcal phages, S25-3 and S13', were used as therapeutic phage candidates. They were assigned to two different lytic phage genera, Twort-like and AHJD-like viruses, based on their morphologies and the N-terminal amino acid sequences of the major capsid proteins. Both had a broad host range and strong lytic activity and showed preservative quality. Administration of these phages alone caused no adverse effects in the silkworm larvae. Moreover, the viruses showed life-prolonging effects in the silkworm larval infection model 10 min, 6 h, 12 h, and 24 h following infection. Such phage effects in the silkworm larval model were almost paralleled to the therapeutic efficacies in mouse models. These results suggest that phages S25-3 and S13' are eligible as therapeutic candidates and that the silkworm larval model is valid for the evaluation of phage therapy as well as mouse models. PMID:23869440

  10. Stage-dependent model for Hantavirus infection: The effect of the initial infection-free period

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; de la Rubia, F. Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s.

  11. Stage-dependent model for Hantavirus infection: the effect of the initial infection-free period.

    PubMed

    Reinoso, José A; de la Rubia, F Javier

    2013-04-01

    We propose a stage-dependent model with constant delay to study the effect of the initial infection-free period on the spread of Hantavirus infection in rodents. We analyze the model under various extreme weather conditions, in the context of the El Niño-La Niña Southern Oscillation phenomenon, and show how these variations determine the evolution of the system significantly. When the scenario corresponds to El Niño, the system presents a demographic explosion and a delayed outbreak of Hantavirus infection, whereas if the scenario is the opposite there is a rapid decline of the population, but with a possible persistence period that may imply a considerable risk for public health, a fact that is in agreement with available field data. We use the model to simulate a historical evolution that resembles the processes that occurred in the 1990s. PMID:23679449

  12. Enhanced susceptibility to infections in a diabetic wound healing model

    PubMed Central

    Hirsch, Tobias; Spielmann, Malte; Zuhaili, Baraa; Koehler, Till; Fossum, Magdalena; Steinau, Hans-Ulrich; Yao, Feng; Steinstraesser, Lars; Onderdonk, Andrew B; Eriksson, Elof

    2008-01-01

    Background Wound infection is a common complication in diabetic patients. The progressive spread of infections and development of drug-resistant strains underline the need for further insights into bacterial behavior in the host in order to develop new therapeutic strategies. The aim of our study was to develop a large animal model suitable for monitoring the development and effect of bacterial infections in diabetic wounds. Methods Fourteen excisional wounds were created on the dorsum of diabetic and non-diabetic Yorkshire pigs and sealed with polyurethane chambers. Wounds were either inoculated with 2 × 108 Colony-Forming Units (CFU) of Staphylococcus aureus or injected with 0.9% sterile saline. Blood glucose was monitored daily, and wound fluid was collected for bacterial quantification and measurement of glucose concentration. Tissue biopsies for microbiological and histological analysis were performed at days 4, 8, and 12. Wounds were assessed for reepithelialization and wound contraction. Results Diabetic wounds showed a sustained significant infection (>105 CFU/g tissue) compared to non-diabetic wounds (p < 0.05) over the whole time course of the experiment. S. aureus-inoculated diabetic wounds showed tissue infection with up to 8 × 107 CFU/g wound tissue. Non-diabetic wounds showed high bacterial counts at day 4 followed by a decrease and no apparent infection at day 12. Epidermal healing in S. aureus-inoculated diabetic wounds showed a significant delay compared with non-inoculated diabetic wounds (59% versus 84%; p < 0.05) and were highly significant compared with healing in non-diabetic wounds (97%; p < 0.001). Conclusion Diabetic wounds developed significantly more sustained infection than non-diabetic wounds. S. aureus inoculation leads to invasive infection and significant wound healing delay and promotes invasive co-infection with endogenous bacteria. This novel wound healing model provides the opportunity to closely assess infections during

  13. Disseminated histoplasmosis mimicking secondary syphilis.

    PubMed

    Pastor, Tony A; Holcomb, Maura J; Motaparthi, Kiran; Grekin, Sarah J; Hsu, Sylvia

    2011-01-01

    A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. Initially secondary syphilis was suspected. However, RPR was negative. Histopathologic examination revealed a lymphocytic infiltrate with numerous intra-histiocytic fungal organisms. GMS and PAS stains were positive, consistent with the diagnosis of histoplasmosis. We report a case of disseminated histoplasmosis clinically mimicking secondary syphilis. PMID:22136866

  14. The host model Galleria mellonella is resistant to taylorellae infection.

    PubMed

    Hébert, L; Rincé, I; Sanna, C; Laugier, C; Rincé, A; Petry, S

    2014-10-01

    The genus Taylorella is composed of two species: (i) Taylorella equigenitalis, the causative agent of CEM, a venereally transmitted infection of Equidae and (ii) Taylorella asinigenitalis, a closely related species considered to be nonpathogenic, although experimental infection of mares with this bacterium resulted in clinical signs of vaginitis, cervicitis or endometritis. Currently, there is a need for an alternative host model to further study the taylorellae species. In this context, we explored Galleria mellonella larvae as potential alternative model hosts for taylorellae. Our results showed that infection of G. mellonella larvae with a high concentration of taylorellae did not induce overt G. mellonella mortality and that taylorellae were not able to proliferate within G. mellonella. In conclusion, G. mellonella larvae are resistant to taylorellae infection and therefore do not constitute a relevant alternative system for studying the virulence of taylorellae species. Significance and impact of the study: To date, the pathogenicity and host colonization capacity of Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM) and T. asinigenitalis, the second species within the Taylorella genus, remain largely unknown. In this study, we evaluated the relevance of Galleria mellonella as an infection model for taylorellae; we showed that G. mellonella are resistant to taylorellae infection and therefore do not constitute a suitable host model for taylorellae. PMID:24945970

  15. Cohabitation reaction-diffusion model for virus focal infections

    NASA Astrophysics Data System (ADS)

    Amor, Daniel R.; Fort, Joaquim

    2014-12-01

    The propagation of virus infection fronts has been typically modeled using a set of classical (noncohabitation) reaction-diffusion equations for interacting species. However, for some single-species systems it has been recently shown that noncohabitation reaction-diffusion equations may lead to unrealistic descriptions. We argue that previous virus infection models also have this limitation, because they assume that a virion can simultaneously reproduce inside a cell and diffuse away from it. For this reason, we build a several-species cohabitation model that does not have this limitation. Furthermore, we perform a sensitivity analysis for the most relevant parameters of the model, and we compare the predicted infection speed with observed data for two different strains of the T7 virus.

  16. Recent developments in experimental animal models of Henipavirus infection.

    PubMed

    Rockx, Barry

    2014-07-01

    Hendra (HeV) and Nipah (NiV) viruses (genus Henipavirus (HNV; family Paramyxoviridae) are emerging zoonotic agents that can cause severe respiratory distress and acute encephalitis in humans. Given the lack of effective therapeutics and vaccines for human use, these viruses are considered as public health concerns. Several experimental animal models of HNV infection have been developed in recent years. Here, we review the current status of four of the most promising experimental animal models (mice, hamsters, ferrets, and African green monkeys) and their suitability for modeling the clinical disease, transmission, pathogenesis, prevention, and treatment for HNV infection in humans. PMID:24488776

  17. Robustness of a cellular automata model for the HIV infection

    NASA Astrophysics Data System (ADS)

    Figueirêdo, P. H.; Coutinho, S.; Zorzenon dos Santos, R. M.

    2008-11-01

    An investigation was conducted to study the robustness of the results obtained from the cellular automata model which describes the spread of the HIV infection within lymphoid tissues [R.M. Zorzenon dos Santos, S. Coutinho, Phys. Rev. Lett. 87 (2001) 168102]. The analysis focused on the dynamic behavior of the model when defined in lattices with different symmetries and dimensionalities. The results illustrated that the three-phase dynamics of the planar models suffered minor changes in relation to lattice symmetry variations and, while differences were observed regarding dimensionality changes, qualitative behavior was preserved. A further investigation was conducted into primary infection and sensitiveness of the latency period to variations of the model’s stochastic parameters over wide ranging values. The variables characterizing primary infection and the latency period exhibited power-law behavior when the stochastic parameters varied over a few orders of magnitude. The power-law exponents were approximately the same when lattice symmetry varied, but there was a significant variation when dimensionality changed from two to three. The dynamics of the three-dimensional model was also shown to be insensitive to variations of the deterministic parameters related to cell resistance to the infection, and the necessary time lag to mount the specific immune response to HIV variants. The robustness of the model demonstrated in this work reinforce that its basic hypothesis are consistent with the three-stage dynamic of the HIV infection observed in patients.

  18. Integrative Model of the Immune Response to a Pulmonary Macrophage Infection: What Determines the Infection Duration?

    PubMed Central

    Go, Natacha; Bidot, Caroline; Belloc, Catherine; Touzeau, Suzanne

    2014-01-01

    The immune mechanisms which determine the infection duration induced by pathogens targeting pulmonary macrophages are poorly known. To explore the impact of such pathogens, it is indispensable to integrate the various immune mechanisms and to take into account the variability in pathogen virulence and host susceptibility. In this context, mathematical models complement experimentation and are powerful tools to represent and explore the complex mechanisms involved in the infection and immune dynamics. We developed an original mathematical model in which we detailed the interactions between the macrophages and the pathogen, the orientation of the adaptive response and the cytokine regulations. We applied our model to the Porcine Respiratory and Reproductive Syndrome virus (PRRSv), a major concern for the swine industry. We extracted value ranges for the model parameters from modelling and experimental studies on respiratory pathogens. We identified the most influential parameters through a sensitivity analysis. We defined a parameter set, the reference scenario, resulting in a realistic and representative immune response to PRRSv infection. We then defined scenarios corresponding to graduated levels of strain virulence and host susceptibility around the reference scenario. We observed that high levels of antiviral cytokines and a dominant cellular response were associated with either short, the usual assumption, or long infection durations, depending on the immune mechanisms involved. To identify these mechanisms, we need to combine the levels of antiviral cytokines, including , and . The latter is a good indicator of the infected macrophage level, both combined provide the adaptive response orientation. Available PRRSv vaccines lack efficiency. By integrating the main interactions between the complex immune mechanisms, this modelling framework could be used to help designing more efficient vaccination strategies. PMID:25233096

  19. Integrative model of the immune response to a pulmonary macrophage infection: what determines the infection duration?

    PubMed

    Go, Natacha; Bidot, Caroline; Belloc, Catherine; Touzeau, Suzanne

    2014-01-01

    The immune mechanisms which determine the infection duration induced by pathogens targeting pulmonary macrophages are poorly known. To explore the impact of such pathogens, it is indispensable to integrate the various immune mechanisms and to take into account the variability in pathogen virulence and host susceptibility. In this context, mathematical models complement experimentation and are powerful tools to represent and explore the complex mechanisms involved in the infection and immune dynamics. We developed an original mathematical model in which we detailed the interactions between the macrophages and the pathogen, the orientation of the adaptive response and the cytokine regulations. We applied our model to the Porcine Respiratory and Reproductive Syndrome virus (PRRSv), a major concern for the swine industry. We extracted value ranges for the model parameters from modelling and experimental studies on respiratory pathogens. We identified the most influential parameters through a sensitivity analysis. We defined a parameter set, the reference scenario, resulting in a realistic and representative immune response to PRRSv infection. We then defined scenarios corresponding to graduated levels of strain virulence and host susceptibility around the reference scenario. We observed that high levels of antiviral cytokines and a dominant cellular response were associated with either short, the usual assumption, or long infection durations, depending on the immune mechanisms involved. To identify these mechanisms, we need to combine the levels of antiviral cytokines, including IFNγ, and IL10. The latter is a good indicator of the infected macrophage level, both combined provide the adaptive response orientation. Available PRRSv vaccines lack efficiency. By integrating the main interactions between the complex immune mechanisms, this modelling framework could be used to help designing more efficient vaccination strategies. PMID:25233096

  20. Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

    NASA Astrophysics Data System (ADS)

    Ulery, Bret D.; Petersen, Latrisha K.; Phanse, Yashdeep; Kong, Chang Sun; Broderick, Scott R.; Kumar, Devender; Ramer-Tait, Amanda E.; Carrillo-Conde, Brenda; Rajan, Krishna; Wannemuehler, Michael J.; Bellaire, Bryan H.; Metzger, Dennis W.; Narasimhan, Balaji

    2011-12-01

    An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens.

  1. Pulsation models for the 0.26 M⊙ star mimicking RR Lyrae pulsator. Model survey for the new class of variable stars

    NASA Astrophysics Data System (ADS)

    Smolec, R.; Pietrzyński, G.; Graczyk, D.; Pilecki, B.; Gieren, W.; Thompson, I.; Stępień, K.; Karczmarek, P.; Konorski, P.; Górski, M.; Suchomska, K.; Bono, G.; Prada, P. G. Moroni; Nardetto, N.

    2013-02-01

    We present non-linear hydrodynamic pulsation models for OGLE-BLG-RRLYR-02792 - a 0.26 M⊙ pulsator, component of the eclipsing binary system, analysed recently by Pietrzyński et al. The star's light and radial velocity curves mimic that of classical RR Lyrae stars, except for the bump in the middle of the ascending branch of the radial velocity curve. We show that the bump is caused by the 2:1 resonance between the fundamental mode and the second overtone - the same mechanism that causes the Hertzsprung bump progression in classical Cepheids. The models allow us to constrain the parameters of the star, in particular to estimate its absolute luminosity (≈33 L⊙) and effective temperature (≈6970 K, close to the blue edge of the instability strip). We conduct a model survey for the new class of low-mass pulsators similar to OGLE-BLG-RRLYR-02792 - products of evolution in the binary systems. We compute a grid of models with masses corresponding to half (or less) of the typical mass of RR Lyrae variable, 0.20 ≤ M ≤ 0.30 M⊙, and discuss the properties of the resulting light and radial velocity curves. Resonant bump progression is clear and may be used to distinguish such stars from classical RR Lyrae stars. We present the Fourier decomposition parameters for the modelled light and radial velocity curves. The expected values of the ϕ31 Fourier phase for the light curves differ significantly from that observed in RR Lyrae stars, which is another discriminant of the new class.

  2. Spilled Gallstones Mimicking Peritoneal Metastases

    PubMed Central

    Loan, William; Carey, Declan P.

    2009-01-01

    Background: Spillage of bile and gallstones due to accidental perforation of the gallbladder wall is often encountered during laparoscopic cholecystectomy. Although spilled stones were once considered harmless, there is increasing evidence that they can result in septic or other potential complications. Case Report: We report a case of spilled gallstones mimicking peritoneal metastases on radiological investigations; diagnosis was confirmed by diagnostic laparoscopy. Conclusion: Every effort should be made to retrieve spilled gallstones during laparoscopic cholecystectomy. When all the stones cannot be retrieved, it should be documented in the patient's medical records to avoid delay in the diagnosis of late complications. Diagnostic laparoscopy is useful when the radiological investigations are inconclusive. PMID:19366546

  3. [Severe PERM syndrom mimicking tetanus].

    PubMed

    Wallet, F; Didelot, A; Delannoy, B; Leray, V; Guerin, C

    2014-01-01

    We report the case of a 55-year-old man without significant medical history admitted to the ICU for a progressive paralysis mimicking life-threatening tetanus. Evolution with classical tetanus treatment was negative, with the need for ventilator support and worsening condition being life threatening. Uncommon evolution revealed a rare glycin antibody-associated hyperekplexia (progressive encephalomyelitis with rigidity syndrome). Patient dramatically improved with immunosuppressive therapy including plasmatic exchanges, cyclophasmid and high dose corticoid infusions. Intensivists should be aware of this very rare syndrome whose treatment is the opposite of tetanus while presentation is very close. Optimal and treatment could lead to prolonged survival. PMID:25168299

  4. Photodynamic therapy of oral Candida infection in a mouse model.

    PubMed

    Freire, Fernanda; Ferraresi, Cleber; Jorge, Antonio Olavo C; Hamblin, Michael R

    2016-06-01

    Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis. PMID:27074245

  5. A cellular automaton model of Schistosoma japonicum infection.

    PubMed

    Wan, Cheng; Liu, Yun; Tu, Xiao-Ming; Zhang, Yuan-Yuan; Xu, Jin-Mei; Lin, Dan-Dan; Luo, Jian-Ping; Chen, Feng; Wu, Hai-Wei

    2013-06-01

    Due to the life cycle complexity of Schistosoma japonicum and the characteristics of schistosomias is immuno-epidemiology, it is very challenging to give a group of certain rules and thus describe the transmission dynamics of S. japonicum with modelling approaches. Most existing epidemiological models for schistosomias is based on differential equations only track average worm burden without taking into account the individual variations, thus bear limitations on individual infection status monitoring and interpretation. In this paper, an improved stochastic model based on cellular automaton (I-SjCA, briefly) has been introduced to describe the transmission dynamics of human schistosomiasis japonica in an endemic area in China. This model reflects the process of the pathogen invasion from exposure to worm development and worm death when the infection is cleared; it also incorporates seasonality of infection, and stochastic behaviour of each individual in the study field. We show that based on the data collected from the 706 study participants, the model-predicted prevalence and intensity of S. japonicum in the 2nd year of investigation is comparable with the observation. Furthermore, we illustrate the use of model for evaluating possible control strategies for schistosomiasis in context of simulated prevalence and individual infection probability. The simulation results suggest that chemotherapy should cover no less than 85% of the S. japonicum infected population to guarantee an effective drug control program, and the best time for annual chemotherapy with praziquantel is the beginning of spring in the endemic area. Our findings indicate that I-SjCA model based on the cellular automaton can effectively simulate the transmission process. It is anticipated that our cellular automaton transmission model can serve as a tool for understanding schistosomiasis transmission dynamics and thus be conductive to build an effective control program. PMID:23462449

  6. Zika Virus Infection and Development of a Murine Model.

    PubMed

    Shah, Ankit; Kumar, Anil

    2016-08-01

    In view of the recent outbreak of Zika virus (ZIKV), there is an urgent need to investigate the pathogenesis of the symptoms associated with ZIKV infection. Since the first identification of the virus in 1947, the pathologies associated with ZIKV infection were thought to be limited with mild illness that presented fever, rashes, muscle aches, and weakness. However, ZIKV infection has been shown to cause Guillain-Barré Syndrome, and numerous cases of congenital microcephaly in children have been reported when pregnant females were exposed to the virus. The severity and the rate of spread of ZIKV in the last year has drawn alarming interest among researchers to investigate murine models to study viral pathogenesis and develop candidate vaccines. A recent study by Lazear and colleagues, in the May 2016 issue of cell host and microbe, is an effort to study the pathogenesis of contemporary and historical virus strains in various mouse models. PMID:27260223

  7. Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model

    PubMed Central

    Slade, Jessica; Hall, Jennifer V.; Kintner, Jennifer; Schoborg, Robert V.

    2016-01-01

    Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

  8. Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model.

    PubMed

    Slade, Jessica; Hall, Jennifer V; Kintner, Jennifer; Schoborg, Robert V

    2016-01-01

    Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

  9. A rabbit model for study of Mycobacterium paratuberculosis infection.

    PubMed Central

    Mokresh, A H; Czuprynski, C J; Butler, D G

    1989-01-01

    Of 21 newborn rabbits inoculated orally with Mycobacterium paratuberculosis ATCC 19698, 13 (62%) became infected, as determined by histopathology and culture. Of the 21 inoculated rabbits, 14 (67%) experienced episodes of intermittent diarrhea, sometimes as early as 5 months after inoculation. Feces varied in consistency from soft-semisolid to watery. The organism was isolated from the sacculus rotundus, vermiform appendix of the cecum, ileum, mesenteric lymph node, and feces of 9 of 21 (43%) M. paratuberculosis-inoculated rabbits 8 to 10 months after inoculation. One infected rabbit gradually became severely emaciated; advanced paratuberculosis was confirmed by culture and histopathology. Of 21 rabbits, 9 (43%) developed multifocal, well-demarcated granulomatous enteritis in the sacculus rotundus and the vermiform appendix of the cecum. There was no significant difference in the rate of infection when the organisms were administered daily for 5 or 10 days in cow milk or broth. There was no discernible effect of pregnancy, parturition, or lactation on the severity of intestinal lesions, clinical signs, or the number of rabbits infected. Complement fixation and delayed-type hypersensitivity skin tests failed to detect infection. The results of this study suggest that newborn rabbits inoculated orally with M. paratuberculosis constitute a useful animal model for the study of paratuberculosis infection. Images PMID:2807547

  10. Caenorhabditis elegans as a model for intracellular pathogen infection

    PubMed Central

    Balla, Keir M.; Troemel, Emily R.

    2014-01-01

    Summary The genetically tractable nematode Caenorhabditis elegans is a convenient host for studies of pathogen infection. With the recent identification of two types of natural intracellular pathogens of C. elegans, this host now provides the opportunity to examine interactions and defence against intracellular pathogens in a whole-animal model for infection. C. elegans is the natural host for a genus of microsporidia, which comprise a phylum of fungal-related pathogens of widespread importance for agriculture and medicine. More recently, C. elegans has been shown to be a natural host for viruses related to the Nodaviridae family. Both microsporidian and viral pathogens infect the C. elegans intestine, which is composed of cells that share striking similarities to human intestinal epithelial cells. Because C. elegans nematodes are transparent, these infections provide a unique opportunity to visualize differentiated intestinal cells in vivo during the course of intracellular infection. Together, these two natural pathogens of C. elegans provide powerful systems in which to study microbial pathogenesis and host responses to intracellular infection. PMID:23617769

  11. A novel total knee arthroplasty infection model in rabbits.

    PubMed

    Craig, Matthew R; Poelstra, Kornelis A; Sherrell, J Christopher; Kwon, Michael S; Belzile, Etienne L; Brown, Thomas E

    2005-09-01

    Infection of biomaterial implants is an expensive and devastating complication of orthopaedic surgery historically ranging from less than 1% in primary total knee arthroplasty (TKA) to 10% in revision TKA. An in vivo animal model was developed to test the efficacy of innovative therapies for the prevention of biomaterial centered infections caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). Twenty-two New Zealand White rabbits were used in this study. After proper anesthesia, a stainless-steel screw with a high molecular weight polyethylene (UHMWPE) washer was cemented in a defect created in the intra-articular, non-articulating portion of the lateral femoral condyle of each knee. After closure of the joint capsule, each knee was inoculated with 0, 10(2), 10(3), or 10(4) colony forming units (CFU) of MRSA. Animals were sacrificed after 7 days at which time joint aspirate, tissues and biomaterial samples were examined for evidence of infection. A total of 42 knees were used for analysis. When saline was injected into the knee, 0/10 of the knees demonstrated evidence of biomaterial centered infection (with the contralateral knee receiving 10(4)CFU MRSA). Four of 10 knees developed a biomaterial centered infection when 10(2)CFU MRSA was introduced. Seven out of 10 knees developed a biomaterial centered infection when either 10(3) or 10(4)CFU MRSA was injected. No evidence of septicemia (positive blood cultures) was found in any animal. This rabbit knee model utilizes commonly employed inexpensive orthopaedic implant materials in an in vivo milieu and provides an effective method for the evaluation of treatments for biomaterial centered infections. PMID:15927441

  12. Eravacycline (TP-434) Is Efficacious in Animal Models of Infection

    PubMed Central

    Murphy, Timothy M.; Slee, Andrew M.; Lofland, Denene; Sutcliffe, Joyce A.

    2015-01-01

    Eravacycline is a novel broad-spectrum fluorocycline antibiotic being developed for a wide range of serious infections. Eravacycline was efficacious in mouse septicemia models, demonstrating 50% protective dose (PD50) values of ≤1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus, including tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes. The PD50 values against Escherichia coli isolates were 1.2 to 4.4 mg/kg q.d. In neutropenic mouse thigh infection models with methicillin-sensitive S. aureus (MSSA) and S. pyogenes, eravacycline produced 2 log10 reductions in CFU at single intravenous (i.v.) doses ranging from 0.2 to 9.5 mg/kg. In a neutropenic mouse lung infection model, eravacycline administered i.v. at 10 mg/kg twice a day (b.i.d.) reduced the level of tetracycline-resistant MRSA in the lung equivalent to that of linezolid given orally (p.o.) at 30 mg/kg b.i.d. At i.v. doses of 3 to 12 mg/kg b.i.d., eravacycline was more efficacious against tetracycline-resistant Streptococcus pneumoniae in a neutropenic lung infection model than linezolid p.o. at 30 mg/kg b.i.d. Eravacycline showed good efficacy at 2 to 10 mg/kg i.v. b.i.d., producing up to a 4.6 log10 CFU reduction in kidney bacterial burden in a model challenged with a uropathogenic E. coli isolate. Eravacycline was active in multiple murine models of infection against clinically important Gram-positive and Gram-negative pathogens. PMID:25691636

  13. Modeling dynamics of HIV infected cells using stochastic cellular automaton

    NASA Astrophysics Data System (ADS)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

    Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

  14. [Modeling and characteristics of liver damage in herpes infection].

    PubMed

    Tereshko, A B; Kolomiets, A G; Grits, M A; Duboĭskaia, G P

    1999-01-01

    An experimental model of herpetic hepatitis is developed, levels and time course of changes in transaminases, the main indicators of lipid metabolism, are characterized, and morphologic features of hepatocyte injury by herpes simplex virus are shown. Liver involvement in herpetic infection is described in detail. PMID:10392435

  15. Choosing an Appropriate Infection Model to Study Quorum Sensing Inhibition in Pseudomonas Infections

    PubMed Central

    Papaioannou, Evelina; Utari, Putri Dwi; Quax, Wim J.

    2013-01-01

    Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review. PMID:24065108

  16. Effects of Infection on Honey Bee Population Dynamics: A Model

    PubMed Central

    Betti, Matt I.; Wahl, Lindi M.; Zamir, Mair

    2014-01-01

    We propose a model that combines the dynamics of the spread of disease within a bee colony with the underlying demographic dynamics of the colony to determine the ultimate fate of the colony under different scenarios. The model suggests that key factors in the survival or collapse of a honey bee colony in the face of an infection are the rate of transmission of the infection and the disease-induced death rate. An increase in the disease-induced death rate, which can be thought of as an increase in the severity of the disease, may actually help the colony overcome the disease and survive through winter. By contrast, an increase in the transmission rate, which means that bees are being infected at an earlier age, has a drastic deleterious effect. Another important finding relates to the timing of infection in relation to the onset of winter, indicating that in a time interval of approximately 20 days before the onset of winter the colony is most affected by the onset of infection. The results suggest further that the age of recruitment of hive bees to foraging duties is a good early marker for the survival or collapse of a honey bee colony in the face of infection, which is consistent with experimental evidence but the model provides insight into the underlying mechanisms. The most important result of the study is a clear distinction between an exposure of the honey bee colony to an environmental hazard such as pesticides or insecticides, or an exposure to an infectious disease. The results indicate unequivocally that in the scenarios that we have examined, and perhaps more generally, an infectious disease is far more hazardous to the survival of a bee colony than an environmental hazard that causes an equal death rate in foraging bees. PMID:25329468

  17. Models for the study of Clostridium difficile infection

    PubMed Central

    Best, Emma L.; Freeman, Jane; Wilcox, Mark H.

    2012-01-01

    Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the concept of colonization resistance, evaluated the role of antibiotics in C. difficile development, explored population dynamics and have been useful in the evaluation of C. difficile treatments. Experiments using models have major advantages over clinical studies and have been indispensible in furthering C. difficile research. It is important for future study programs to carefully consider the approach to use and therefore be better placed to inform the design and interpretation of clinical studies. PMID:22555466

  18. Experimental Models of Ocular Infection with Toxoplasma Gondii

    PubMed Central

    Dukaczewska, Agata; Tedesco, Roberto; Liesenfeld, Oliver

    2015-01-01

    Ocular toxoplasmosis is a vision-threatening disease and the major cause of posterior uveitis worldwide. In spite of the continuing global burden of ocular toxoplasmosis, many critical aspects of disease including the therapeutic approach to ocular toxoplasmosis are still under debate. To assist in addressing many aspects of the disease, numerous experimental models of ocular toxoplasmosis have been established. In this article, we present an overview on in vitro, ex vivo, and in vivo models of ocular toxoplasmosis available to date. Experimental studies on ocular toxoplasmosis have recently focused on mice. However, the majority of murine models established so far are based on intraperitoneal and intraocular infection with Toxoplasma gondii. We therefore also present results obtained in an in vivo model using peroral infection of C57BL/6 and NMRI mice that reflects the natural route of infection and mimics the disease course in humans. While advances have been made in ex vivo model systems or larger animals to investigate specific aspects of ocular toxoplasmosis, laboratory mice continue to be the experimental model of choice for the investigation of ocular toxoplasmosis. PMID:26716018

  19. Immunity to Polyomavirus Infection: The Polyoma Virus-Mouse Model

    PubMed Central

    Swanson, Phillip A.; Lukacher, Aron E.; Szomolanyi-Tsuda, Eva

    2009-01-01

    A ubiquitous clinically silent murine pathogen, polyoma virus has enjoyed long-term co-evolution with the mouse, a highly tractable and genetically and immunologically informative small animal model. Thus, polyoma virus has provided a valuable experimental construct to decipher the host immune mechanisms that come into play to control systemic low-level persistent viral infections. Impaired immunosurveillance for infected cells puts the murine host at risk both to injury resulting from excessive direct virus cytolysis and development of virus-induced tumors. In this review, we present our current understanding of the multifaceted immune response invoked by the mouse to maintain détente with this potentially deleterious persistent natural pathogen, and discuss implications of these studies for therapeutic interventions for human polyomavirus infection. PMID:19505652

  20. Black hole mimickers: Regular versus singular behavior

    SciTech Connect

    Lemos, Jose P. S.; Zaslavskii, Oleg B.

    2008-07-15

    Black hole mimickers are possible alternatives to black holes; they would look observationally almost like black holes but would have no horizon. The properties in the near-horizon region where gravity is strong can be quite different for both types of objects, but at infinity it could be difficult to discern black holes from their mimickers. To disentangle this possible confusion, we examine the near-horizon properties, and their connection with far away asymptotic properties, of some candidates to black mimickers. We study spherically symmetric uncharged or charged but nonextremal objects, as well as spherically symmetric charged extremal objects. Within the uncharged or charged but nonextremal black hole mimickers, we study nonextremal {epsilon}-wormholes on the threshold of the formation of an event horizon, of which a subclass are called black foils, and gravastars. Within the charged extremal black hole mimickers we study extremal {epsilon}-wormholes on the threshold of the formation of an event horizon, quasi-black holes, and wormholes on the basis of quasi-black holes from Bonnor stars. We elucidate whether or not the objects belonging to these two classes remain regular in the near-horizon limit. The requirement of full regularity, i.e., finite curvature and absence of naked behavior, up to an arbitrary neighborhood of the gravitational radius of the object enables one to rule out potential mimickers in most of the cases. A list ranking the best black hole mimickers up to the worst, both nonextremal and extremal, is as follows: wormholes on the basis of extremal black holes or on the basis of quasi-black holes, quasi-black holes, wormholes on the basis of nonextremal black holes (black foils), and gravastars. Since in observational astrophysics it is difficult to find extremal configurations (the best mimickers in the ranking), whereas nonextremal configurations are really bad mimickers, the task of distinguishing black holes from their mimickers seems to

  1. Persistent Salmonellosis Causes Pancreatitis in a Murine Model of Infection

    PubMed Central

    Hall, Jason C.; Thotakura, Gangadaar; Crawford, Howard C.; van der Velden, Adrianus W. M.

    2014-01-01

    Pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma, is a serious, widespread medical condition usually caused by alcohol abuse or gallstone-mediated ductal obstruction. However, many cases of pancreatitis are of an unknown etiology. Pancreatitis has been linked to bacterial infection, but causality has yet to be established. Here, we found that persistent infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) was sufficient to induce pancreatitis reminiscent of the human disease. Specifically, we found that pancreatitis induced by persistent S. Typhimurium infection was characterized by a loss of pancreatic acinar cells, acinar-to-ductal metaplasia, fibrosis and accumulation of inflammatory cells, including CD11b+ F4/80+, CD11b+ Ly6Cint Ly6G+ and CD11b+ Ly6Chi Ly6G− cells. Furthermore, we found that S. Typhimurium colonized and persisted in the pancreas, associated with pancreatic acinar cells in vivo, and could invade cultured pancreatic acinar cells in vitro. Thus, persistent infection of mice with S. Typhimurium may serve as a useful model for the study of pancreatitis as it relates to bacterial infection. Increased knowledge of how pathogenic bacteria can cause pancreatitis will provide a more integrated picture of the etiology of the disease and could lead to the development of new therapeutic approaches for treatment and prevention of pancreatitis and pancreatic ductal adenocarcinoma. PMID:24717768

  2. Modeling risk of occupational zoonotic influenza infection in swine workers.

    PubMed

    Paccha, Blanca; Jones, Rachael M; Gibbs, Shawn; Kane, Michael J; Torremorell, Montserrat; Neira-Ramirez, Victor; Rabinowitz, Peter M

    2016-08-01

    Zoonotic transmission of influenza A virus (IAV) between swine and workers in swine production facilities may play a role in the emergence of novel influenza strains with pandemic potential. Guidelines to prevent transmission of influenza to swine workers have been developed but there is a need for evidence-based decision-making about protective measures such as respiratory protection. A mathematical model was applied to estimate the risk of occupational IAV exposure to swine workers by contact and airborne transmission, and to evaluate the use of respirators to reduce transmission.  The Markov model was used to simulate the transport and exposure of workers to IAV in a swine facility. A dose-response function was used to estimate the risk of infection. This approach is similar to methods previously used to estimate the risk of infection in human health care settings. This study uses concentration of virus in air from field measurements collected during outbreaks of influenza in commercial swine facilities, and analyzed by polymerase chain reaction.  It was found that spending 25 min working in a barn during an influenza outbreak in a swine herd could be sufficient to cause zoonotic infection in a worker. However, this risk estimate was sensitive to estimates of viral infectivity to humans. Wearing an excellent fitting N95 respirator reduced this risk, but with high aerosol levels the predicted risk of infection remained high under certain assumptions.  The results of this analysis indicate that under the conditions studied, swine workers are at risk of zoonotic influenza infection. The use of an N95 respirator could reduce such risk. These findings have implications for risk assessment and preventive programs targeting swine workers. The exact level of risk remains uncertain, since our model may have overestimated the viability or infectivity of IAV. Additionally, the potential for partial immunity in swine workers associated with repeated low

  3. The rabbit as an infection model for equine proliferative enteropathy

    PubMed Central

    Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

    2013-01-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  4. The rabbit as an infection model for equine proliferative enteropathy.

    PubMed

    Sampieri, Francesca; Allen, Andrew L; Pusterla, Nicola; Vannucci, Fabio A; Antonopoulos, Aphroditi J; Ball, Katherine R; Thompson, Julie; Dowling, Patricia M; Hamilton, Don L; Gebhart, Connie J

    2013-04-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  5. Odontogenic Keratocyst Mimicking Paradental Cyst

    PubMed Central

    Borgonovo, Andrea Enrico; Bernardini, Luigi; Francinetti, Paola

    2014-01-01

    Objective. The aim of this paper is to present an uncommon clinical and radiographic aspect of odontogenic keratocyst (OKC) mimicking paradental cyst. Methods. A 32-year-old female patient showed a well-delimited radiolucent lesion connected with the root of the left third molar with close anatomical relationship with the mandibular canal. The clinical, radiographic, and anamnestic features lead us to diagnose a paradental cyst that was treated by enucleation after extraction of the partially impacted tooth. Results. Histological analysis showed typical histological features of PKC such as the presence of a lining of stratified squamous epithelium with a well-defined basal layer of palisading columnar of cuboidal cells. Conclusion. Initial X-ray analysis and the position of the lesion related to the third mandibular tooth caused us to mistakenly diagnose a paradental cyst. We were only able to identify the cyst as an PKC rather than a paradental cyst after histological analysis. PMID:25114809

  6. Subaortic membrane mimicking hypertrophic cardiomyopathy.

    PubMed

    Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

    2015-01-01

    A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. PMID:26538250

  7. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

    PubMed Central

    Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

    2015-01-01

    Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

  8. Hendra and Nipah Infection: Pathology, Models and Potential Therapies

    PubMed Central

    Vigant, Frederic; Lee, Benhur

    2011-01-01

    The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeutic treatments for henipavirus infections. Although ribavirin was empirically used and seemed beneficial during the biggest outbreak caused by one of these viruses, the Nipah virus, its efficacy is disputed in light of its lack of efficacy in several animal models of henipavirus infection. Nevertheless, because of its highly pathogenic nature, much effort has been spent in developing anti-henipavirus therapeutics. In this review we describe the unique features of henipavirus infections and the different strategies and animal models that have been developed so far in order to identify and test potential drugs to prevent or treat henipavirus infections. Some of these components have the potential to be broad-spectrum antivirals as they target effectors of viral pathogenecity common to other viruses. We will focus on small molecules or biologics, rather than vaccine strategies, that have been developed as anti-henipaviral therapeutics. PMID:21488828

  9. The challenges of modelling antibody repertoire dynamics in HIV infection

    SciTech Connect

    Luo, Shishi; Perelson, Alan S.

    2015-07-20

    Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selection and compare this to the observed temporal patterns of antibody evolution in HIV infection. In addition, we describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.

  10. The challenges of modelling antibody repertoire dynamics in HIV infection

    DOE PAGESBeta

    Luo, Shishi; Perelson, Alan S.

    2015-07-20

    Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selectionmore » and compare this to the observed temporal patterns of antibody evolution in HIV infection. In addition, we describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.« less

  11. Subcutaneous Phaeohyphomycosis Due to Pyrenochaeta romeroi Mimicking a Synovial Cyst

    PubMed Central

    Dinh, Aurélien; Levy, Bruno; Bouchand, Frédérique; Davido, Benjamin; Duran, Clara; Cristi, Marin; Felter, Adrien; Salomon, Jérôme; Ait Ammar, Nawel

    2016-01-01

    Opportunistic subcutaneous fungal infections are increasing nowadays due to the growing number of medical conditions causing immunosuppression, especially organ transplant. The incidence rate of subcutaneous phaeohyphomycosis is very low. Most studies found are case reports. They showed a wide variation of clinical presentations. Pyrenochaeta romeroi, a fungus from the Dematiaceae group is a saprophyte found in soil and plants and a possible causative agent of phaeohyphomycosis. We present a rare case of subcutaneous phaeohyphomycosis caused by P. romeroi mimicking a synovial cyst in a diabetic patient.

  12. A Giant Mature Cystic Teratoma Mimicking a Pleural Effusion

    PubMed Central

    Dorterler, Mustafa Erman; Boleken, Mehmet Emin; Koçarslan, Sezen

    2016-01-01

    The vast majority of teratomas originating from more than a single germ layer are benign. Often, such teratomas are initially asymptomatic. Later symptoms are caused by the weight per se of the teratoma and include chest pain, cough, dyspnea, and/or recurrent attacks of pneumonia. A mediastinal teratoma is treated by total surgical resection of the mass. Here, we report a case of giant mature cystic teratoma mimicking a pleural effusion in the thorax at the 7-month-old female patient with a symptom of persistent pulmonary infection and tachypnea. PMID:26942032

  13. Animal models for viral infection and cell exhaustion

    PubMed Central

    McGary, Colleen S.; Silvestri, Guido; Paiardini, Mirko

    2014-01-01

    Purpose of review Despite eliciting an early antiviral T cell response, HIV-specific T cells are unable to prevent disease progression, partly due to their loss of effector functions, known as T cell exhaustion. Restoring this T cell functionality represents a critical step for regaining immunological control of HIV-1 replication, and may be fundamental for the development of a functional cure for HIV. In this context, the use of animal models is invaluable for evaluating the efficacy and mechanisms of novel therapeutics aimed at reinvigorating T cell functions. Recent findings While non-human primates continue to be a mainstay for studying HIV pathogenesis and therapies, recent advances in humanized mouse models have improved their ability to recapitulate the features of cell exhaustion during HIV infection. Targeting coinhibitory receptors in HIV- and SIV-infected animals has resulted in viral load reductions, presumably by reinvigorating the effector functions of T cells. Additionally, studies combining PD-1 blockade with suppressive ART provide further support of the use of coinhibitory receptor blockades in restoring T cell function by delaying viral load rebound upon ART interruption. Future in vivo studies should build on recent in vitro data supporting the simultaneous targeting of multiple regulators of cell exhaustion. Summary In this review, we describe the most recent advances in the use of animal models for the study of cell exhaustion following HIV/SIV infection. These findings suggest that the use of animal models is increasingly critical in translating immunotherapeutics into clinical practice. PMID:25023622

  14. Drug testing in mouse models of tuberculosis and nontuberculous mycobacterial infections.

    PubMed

    Nikonenko, Boris V; Apt, Alexander S

    2013-05-01

    Mice as a species are susceptible to tuberculosis infection while mouse inbred strains present wide spectrum of susceptibility/resistance to this infection. However, non-tuberculosis Mycobacterial infections usually cannot be modeled in mice of common inbred strains. Introduction of specific properties, such as gene mutations, recombinants, targeted gene knockouts significantly extended the use of mice to mimic human Mycobacterial infections, including non-tuberculosis ones. This review describes the available mouse models of tuberculosis and non-tuberculosis infections and drug therapy in these models. Mouse models of non-tuberculosis infections are significantly less developed than tuberculosis models, hampering the development of therapies. PMID:23491715

  15. Treatment model of dengue hemorrhagic fever infection in human body

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  16. Bone tumor mimickers: A pictorial essay

    PubMed Central

    Mhuircheartaigh, Jennifer Ni; Lin, Yu-Ching; Wu, Jim S

    2014-01-01

    Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety. PMID:25114385

  17. Modeling Granulomas in Response to Infection in the Lung.

    PubMed

    Hao, Wenrui; Schlesinger, Larry S; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The 'strength' of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the 'switching time', namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  18. A Susceptible Mouse Model for Zika Virus Infection

    PubMed Central

    Rayner, Emma; Atkinson, Barry; Hall, Graham; Watson, Robert J.; Bosworth, Andrew; Bonney, Laura C.; Kitchen, Samantha; Hewson, Roger

    2016-01-01

    Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129) mice and the parent strain (129Sv/Ev) after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with widespread viral RNA detection in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels than those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus A129 mice represent a suitable, and urgently required, small animal model for the testing of vaccines and antivirals. PMID:27149521

  19. Mathematical model for Dengue with three states of infection

    NASA Astrophysics Data System (ADS)

    Hincapie, Doracelly; Ospina, Juan

    2012-06-01

    A mathematical model for dengue with three states of infection is proposed and analyzed. The model consists in a system of differential equations. The three states of infection are respectively asymptomatic, partially asymptomatic and fully asymptomatic. The model is analyzed using computer algebra software, specifically Maple, and the corresponding basic reproductive number and the epidemic threshold are computed. The resulting basic reproductive number is an algebraic synthesis of all epidemic parameters and it makes clear the possible control measures. The microscopic structure of the epidemic parameters is established using the quantum theory of the interactions between the atoms and radiation. In such approximation, the human individual is represented by an atom and the mosquitoes are represented by radiation. The force of infection from the mosquitoes to the humans is considered as the transition probability from the fundamental state of atom to excited states. The combination of computer algebra software and quantum theory provides a very complete formula for the basic reproductive number and the possible control measures tending to stop the propagation of the disease. It is claimed that such result may be important in military medicine and the proposed method can be applied to other vector-borne diseases.

  20. A Susceptible Mouse Model for Zika Virus Infection.

    PubMed

    Dowall, Stuart D; Graham, Victoria A; Rayner, Emma; Atkinson, Barry; Hall, Graham; Watson, Robert J; Bosworth, Andrew; Bonney, Laura C; Kitchen, Samantha; Hewson, Roger

    2016-05-01

    Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129) mice and the parent strain (129Sv/Ev) after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with widespread viral RNA detection in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels than those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus A129 mice represent a suitable, and urgently required, small animal model for the testing of vaccines and antivirals. PMID:27149521

  1. Modeling Granulomas in Response to Infection in the Lung

    PubMed Central

    Hao, Wenrui; Schlesinger, Larry S.; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The ‘strength’ of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the ‘switching time’, namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  2. The natural alternative: protozoa as cellular models for Legionella infection.

    PubMed

    Hoffmann, Christine; Harrison, Christopher F; Hilbi, Hubert

    2014-01-01

    The severe pneumonia known as Legionnaires' disease occurs following infection by the Gram-negative bacterium Legionella pneumophila. Normally resident in fresh-water sources, Legionella are subject to predation by eukaryotic phagocytes such as amoeba and ciliates. To counter this, L. pneumophila has evolved a complex system of effector proteins which allow the bacteria to hijack the phagocytic vacuole, hiding and replicating within their erstwhile killers. These same mechanisms allow L. pneumophila to hijack another phagocyte, lung-based macrophages, which thus avoids a vital part of the immune system and leads to infection. The course of infection can be divided into five main categories: pathogen uptake, formation of the replication-permissive vacuole, intracellular replication, host cell response, and bacterial exit. L. pneumophila effector proteins target every stage of this process, interacting with secretory, endosomal, lysosomal, retrograde and autophagy pathways, as well as with mitochondria. Each of these steps can be studied in protozoa or mammalian cells, and the knowledge gained can be readily applied to human pathogenicity. Here we describe the manner whereby L. pneumophila infects host protozoa, the various techniques which are available to analyse these processes and the implications of this model for Legionella virulence and the pathogenesis of Legionnaires' disease. PMID:24168696

  3. Modelling the spatial distribution of Echinococcus multilocularis infection in foxes.

    PubMed

    Pleydell, D R J; Raoul, F; Tourneux, F; Danson, F M; Graham, A J; Craig, P S; Giraudoux, P

    2004-08-01

    Alveolar echinococcosis is a rare but fatal disease in humans and is caused by the fox tapeworm Echinococcus multilocularis. The densities of fox and grassland rodent populations and the interactions between them influence E. multilocularis transmission rates in Europe. Successful rabies control has caused fox populations and E. multilocularis prevalence rates to increase in many European countries. The potential increase of the infection pressure on the human population motivates the monitoring of the infection status of foxes over space and time. Detection of E. multilocularis antigen levels in fox faecal samples collected in the field might provide a pragmatic methodology for epidemiological surveillance of the infection status in wildlife hosts across large areas, as well as providing an indication of the spatial distribution of infected faeces contaminating the environment. In this paper, a spatial analysis of antigen levels detected in faeces collected in the Franche-Comté region of eastern France is presented. In Franche-Comté, rodent outbreaks have been observed to originate in areas rich in grassland. Spatial trends in fox infection levels were modelled here as a function of the composition ratio of grassland in the landscape derived from the CORINE land-cover map. Kriging models incorporating the grassland trend term were compared to a variety of models in which five alternative trend expressions were used: the alternative trend expressions included linear and quadratic polynomials on the x and y coordinates with and without a grassland term, and a constant mean model. Leave-one-out cross-validation indicated that the estimation errors of kriging with a trend models were significantly lower when the trend expression contained the grassland index term only. The relationship between observed and predicted antigen levels was strongest when the estimated range of autocorrelation was within the home range size of a single fox. The over-dispersion of E

  4. Global dynamics of cholera models with differential infectivity.

    PubMed

    Shuai, Zhisheng; van den Driessche, P

    2011-12-01

    A general compartmental model for cholera is formulated that incorporates two pathways of transmission, namely direct and indirect via contaminated water. Non-linear incidence, multiple stages of infection and multiple states of the pathogen are included, thus the model includes and extends cholera models in the literature. The model is analyzed by determining a basic reproduction number R0 and proving, by using Lyapunov functions and a graph-theoretic result based on Kirchhoff's Matrix Tree Theorem, that it determines a sharp threshold. If R0≤1, then cholera dies out; whereas if R0>1, then the disease tends to a unique endemic equilibrium. When input and death are neglected, the model is used to determine a final size equation or inequality, and simulations illustrate how assumptions on cholera transmission affect the final size of an epidemic. PMID:22001141

  5. Scintigraphy of infected total hip arthroplasty (THA): A canine model

    SciTech Connect

    Merkel, K.D.; Brown, M.L.; Fitzgerald, R.H.; Dewanjee, M.K.

    1984-01-01

    Differentiating low-grade sepsis from aseptic loosening of an orthopedic prosthesis is difficult. This study was designed to compare the ability of Tc-99m-HMDP, Ga-67, and In-111 leukocytes (WC) to differentiate low-grade sepsis from aseptic THA component loosening in a canine model. A canine THA was implanted in 14 dogs. Six dogs were given infected femoral components by injecting 10/sup 5/ colony-forming units of Staphylococcus aureus into the femoral canal 6y0 to 90 seconds prior to cementing. Four dogs had an aseptic loose femoral component, and four dogs had an aseptic tight femoral component (control). At six months all dogs were evaluated with X-ray, lab scintigraphy, and tissue quantitation of each tracer. Diagnosis was confirmed by histology and quantitative microbiology. White blood cell counts and differentials were normal in all dogs, and in only one out of six infected dogs was the sedimentation rate abnormal. X-rays were interpreted as possible infection in five dogs and probable infection in only one dog. In-111 WBC scans were more accurate than sequential Tc-Ga scans (sensitivity 94% vs 61%, specificity 86% vs 71% accuracy 90% vs 67%). Quantitative counting of gamma camera data and tissue samples demonstrated significantly (P < .01) higher accumulation of In-111 WBC about the infected than the loose or control component. No significant difference was demonstrated between the loose and septic components with TC-HMDP or Ga. These results correlate well and confirm our clinical data that In-111 WBC scanning is accurate and useful in the workup of the painful orthopedic prosthesis.

  6. An experimental infection model for Tetrameres americana (Cram 1927).

    PubMed

    Fink, M; Permin, A; Jensen, K-M V; Bresciani, J; Magwisha, H B

    2005-02-01

    An experimental infection model for the heteroecious spiruid nematode Tetrameres americana (Cram 1927) was developed. The cockroach Blattella germanica (L.) and the locust Locusta migratoria (L.) were found to serve as intermediate hosts for the parasite. T. americana larvae developed to full maturity in these intermediate hosts and were infective to young Lohman Brown chickens after 32 days in the cockroach and 28 days in the locust. The maximum length of the larvae was reached in the insects at 28-30 degrees C after 10-15 days, at which time the larvae measured up to 2.2 mm. The parasite did not develop in the cockroach Periplaneta americana (L.), the woodlouse Oniscus asellus (L.), or the pupal stage of the giant mealworm Zophobas morio (Fabricius). Trials in which chickens were infected directly without an intermediate host failed. Infection of 24 chickens with a dosage of 100 larvae was followed by weekly post-mortems until day 48 post-infection (p.i.) and used to describe the development of T. americana. The average establishment rate (%) and the average worm burden varied from 16.5 to 30.8. The total numbers of parasites recovered ranged from 9 to 40. During mating, in the first 2 weeks p.i. females and males were equally abundant, whereas from day 20 p.i. twice as many females were recovered. From day 13 p.i. the females average length fluctuated between 2.6 and 3.7 mm, whereas they reached their maximum width of 2.4 mm on day 48 p.i. Males reached their full length after 27 days p.i. and measured up to 6.7 mm. PMID:15616857

  7. Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model

    PubMed Central

    Slade, Jessica A.; Hall, Jennifer V.; Kintner, Jennifer; Phillips-Campbell, Regenia; Schoborg, Robert V.

    2016-01-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection. PMID:27486990

  8. Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.

    PubMed

    Slade, Jessica A; Hall, Jennifer V; Kintner, Jennifer; Phillips-Campbell, Regenia; Schoborg, Robert V

    2016-01-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection. PMID:27486990

  9. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor.

    PubMed

    Tanrıverdi, Elif; Özgül, Mehmet Akif; Uzun, Oğuz; Gül, Şule; Çörtük, Mustafa; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  10. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor

    PubMed Central

    Özgül, Mehmet Akif; Uzun, Oğuz; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  11. Humanlike Robots - Synthetically Mimicking Humans

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Yoseph

    2012-01-01

    Nature inspired many inventions and the field of technology that is based on the mimicking or inspiration of nature is widely known as Biomimetics and it is increasingly leading to many new capabilities. There are numerous examples of biomimetic successes including the copying of fins for swimming, and the inspiration of the insects and birds flight. More and more commercial implementations of biomimetics are appearing and behaving lifelike and applications are emerging that are important to our daily life. Making humanlike robots is the ultimate challenge to biomimetics and, for many years, it was considered science fiction, but such robots are becoming an engineering reality. Advances in producing such robot are allowing them to perform impressive functions and tasks. The development of such robots involves addressing many challenges and is raising concerns that are related to fear of their application implications and potential ethical issues. In this paper, the state-of-the-art of humanlike robots, potential applications and challenges will be reviewed.

  12. Intravital models of infection lay the foundation for tissue microbiology.

    PubMed

    Choong, Ferdinand X; Regberg, Jakob; Udekwu, Klas I; Richter-Dahlfors, Agneta

    2012-04-01

    In complex environments, such as those found in the human host, pathogenic bacteria constantly battle the unfavorable conditions imposed by the host response to their presence. During Escherichia coli-induced pyelonephritis, a cascade of events are shown in an intravital animal model to occur in a timely and sequential manner, representing the dynamic interplay between host and pathogen. Today, intravital techniques allow for observing infection in the living host. At resolutions almost on the single-cell level, improved detection methods offer a movie-like description of infection dynamics. Tissue microbiology involves monitoring host-pathogen interaction within the dynamic microecology of infectious sites in the live host. This new field holds great promise for insightful research into microbial disease intervention strategies. PMID:22439728

  13. Callithrix penicillata: a feasible experimental model for dengue virus infection.

    PubMed

    Ferreira, Milene Silveira; de Castro, Paulo Henrique Gomes; Silva, Gilmara Abreu; Casseb, Samir Mansur Moraes; Dias Júnior, Antônio Gregório; Rodrigues, Sueli Guerreiros; Azevedo, Raimunda do Socorro da Silva; Costa e Silva, Matheus Fernandes; Zauli, Danielle Alves Gomes; Araújo, Márcio Sobreira Silva; Béla, Samantha Ribeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Vasconcelos, Pedro Fernando da Costa

    2014-01-01

    Although the murine models have the feasibility to reproduce some signs of dengue Virus (DENV) infection, the use of isogenic hosts with polarized immune response patterns does not reproduce the particularities of human disease. Our goal was to investigate the kinetics of peripheral blood biomarkers in immunocompetent Callithrix penicillata non-human primates subcutaneously infected with DENV-3. The viral load of infected animals was determinated by quantitative real time PCR. Measurements of DENV-3/IgM were performed, and several parameters were assessed by hemogram: red blood cells count, hemoglobin, hematocrit, white blood cells count, neutrophils, monocytes, lymphocytes, and platelets count. The coagulogram was performed by prothrombin time (PT), and activated partial thromboplastin time (APTT) assays. The renal function was monitored by urea and creatinine, and the liver function by the aspartate (AST), and alanine (ALT) aminotransferases. Also, the level of the cytokines IL-6, TNF-α, IL-2, IFN-γ, IL-4 and IL-5 was quantified during the experimental study. Data analysis was performed considering relevant differences when baseline fold changes were found outside from 0.75 to 1.5 range. Our data demonstrated that infected animals presented relevant signs of dengue disease, including peaks of viremia at 5 days-post-infection (dpi), peaks of anti-DENV-3 IgM at 15 dpi and hemaglutination inhibition assay (HIA) from 15 to at 60 dpi. Despite early monocytosis, slight neutrophilia and lymphocytosis, animals developed persistent leucopenia starting at 4 dpi. Anemia episodes were steady at 3-4 dpi. Patent thrombocytopenia was observed from 1 to 15 dpi with sporadic decrease of APTT. A substantial increase of ALT and AST was observed with higher peak at 4 dpi. Moreover, early increases of TNF-alpha and IFN-gamma besides late increase of IFN-gamma were observed. The analysis of biomarkers network pointed out two relevant strong axes during early stages of dengue fever

  14. A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

    PubMed Central

    Ng, Lisa FP; Hibberd, Martin L; Ooi, Eng-Eong; Tang, Kin-Fai; Neo, Soek-Ying; Tan, Jenny; Krishna Murthy, Karuturi R; Vega, Vinsensius B; Chia, Jer-Ming; Liu, Edison T; Ren, Ee-Chee

    2004-01-01

    Background The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. Methods PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. Results We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. Conclusions The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis. PMID:15357874

  15. Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Huang Lichao; Weng Shaoping; Wang Jing; Lin Ting; Tang Junliang; Li Zhongsheng; Lu Qingxia; Xia Qiong; Yu Xiaoqiang; He Jianguo

    2010-10-25

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} and tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.

  16. Cryptococcal Brainstem Abscess Mimicking Brain Tumors in an Immunocompetent Patient

    PubMed Central

    Hur, Jong Hee; Kim, Jang-Hee; Park, Seoung Woo

    2015-01-01

    Usually fungal infections caused by opportunistic and pathogenic fungi had been an important cause of morbidity and mortality among immunocompromised patients. However clinical data and investigations for immunocompetent pathogenic fungal infections had been rare and neglected into clinical studies. Especially Cryptococcal brainstem abscess cases mimicking brain tumors were also much more rare. So we report this unusual case. This 47-year-old man presented with a history of progressively worsening headache and nausea for 1 month and several days of vomituritions before admission. Neurological and laboratory examinations performed demonstrated no abnormal findings. Previously he was healthy and did not have any significant medical illnesses. A CT and MRI scan revealed enhancing 1.8×1.7×2.0 cm mass lesion in the left pons having central necrosis and peripheral edema compressing the fourth ventricle. And also positron emission tomogram scan demonstrated a hot uptake of fluoro-deoxy-glucose on the brainstem lesion without any evidences of systemic metastasis. Gross total mass resection was achieved with lateral suboccipital approach with neuronavigation system. Postoperatively he recovered without any neurological deficits. Pathologic report confirmed Cryptococcus neoformans and he was successively treated with antifungal medications. This is a previously unreported rare case of brainstem Cryptococcal abscess mimicking brain tumors in immunocompetent host without having any apparent typical meningeal symptoms and signs with resultant good neurosurgical recovery. PMID:25674344

  17. Animal models of enterovirus 71 infection: applications and limitations.

    PubMed

    Wang, Ya-Fang; Yu, Chun-Keung

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

  18. ASSESSMENT OF IMMUNOTOXICITY WITH THE PARASITIC INFECTION MODEL TRICHINELLA SPIRALIS

    EPA Science Inventory

    Resistance to trichinella spiralis is known to require an intact immune system. his chapter presents an overview of the infection, the host response to infection, and methods for assessing infection in rats and mice.

  19. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    NASA Astrophysics Data System (ADS)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  20. Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

    PubMed Central

    Dutta, Noton K.

    2014-01-01

    SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI. PMID:25184558

  1. Animal models for Ebola and Marburg virus infections.

    PubMed

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  2. Measurement of guided mode wavenumbers in soft tissue-bone mimicking phantoms using ultrasonic axial transmission.

    PubMed

    Chen, Jiangang; Foiret, Josquin; Minonzio, Jean-Gabriel; Talmant, Maryline; Su, Zhongqing; Cheng, Li; Laugier, Pascal

    2012-05-21

    Human soft tissue is an important factor that influences the assessment of human long bones using quantitative ultrasound techniques. To investigate such influence, a series of soft tissue-bone phantoms (a bone-mimicking plate coated with a layer of water, glycerol or silicon rubber) were ultrasonically investigated using a probe with multi-emitter and multi-receiver arrays in an axial transmission configuration. A singular value decomposition signal processing technique was applied to extract the frequency-dependent wavenumbers of several guided modes. The results indicate that the presence of a soft tissue-mimicking layer introduces additional guided modes predicted by a fluid waveguide model. The modes propagating in the bone-mimicking plate covered by the soft-tissue phantom are only slightly modified compared to their counterparts in the free bone-mimicking plate, and they are still predicted by an elastic transverse isotropic two-dimensional waveguide. Altogether these observations suggest that the soft tissue-bone phantoms can be modeled as two independent waveguides. Even in the presence of the overlying soft tissue-mimicking layer, the modes propagating in the bone-mimicking plate can still be extracted and identified. These results suggest that our approach can be applied for the purpose of the characterization of the material and structural properties of cortical bone. PMID:22538382

  3. Acute tuberculous myopericarditis mimicking acute myocardial infarction: A case report and literature review

    PubMed Central

    REN, MANYI; ZHANG, CHUNSHENG; ZHANG, XIAOJUAN; ZHONG, JINGQUAN

    2016-01-01

    A number of cases of acute myopericarditis mimicking acute myocardial infarction (AMI) have previously been reported in the literature. However, to the best of our knowledge, such a case resulting from Mycobacterium tuberculosis infection has not previously been described. The present study reports the case of a 21-year-old male patient presenting with acute chest pain, in whom focal ST-segment elevation and elevated cardiac enzymes mimicked a diagnosis of AMI. However, acute tuberculous myopericarditis was diagnosed on the basis of a variety of imaging examinations, laboratory tests, as well as the changes observed in electrocardiograms (ECGs) and in the cardiac enzyme levels. The case highlights the importance of a detailed collection of medical history, comprehensive explanations of serial ECGs, thoracic computed tomography, echocardiogram and coronary angiography in the diagnosis and differentiation of acute tuberculous myopericarditis mimicking AMI. PMID:27284323

  4. Dengue human infection models to advance dengue vaccine development.

    PubMed

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. PMID:26424605

  5. A New Mouse Model of Limb-Girdle Muscular Dystrophy Type 2I Homozygous for the Common L276I Mutation Mimicking the Mild Phenotype in Humans.

    PubMed

    Krag, Thomas O; Vissing, John

    2015-12-01

    Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the Fukutin-related protein (FKRP) gene, leading to inadequate glycosylation of α-dystroglycan, an important protein linking the extracellular matrix to the cytoskeleton. We created a mouse model of the common FKRP L276I mutation and a hemizygous FKRP L276I knockout model. We studied histopathology and protein expression in the models at different ages and found that homozygous FKRP L276I mice developed a mild progressive myopathy with increased muscle regeneration and fibrosis starting from 1 year of age. This was likely caused by progressive loss of α-dystroglycan-specific glycosylation, which was decreased by 78% at 20 months. The homozygous FKRP knockout was embryonic lethal, but the hemizygous L276I model resembled the homozygous FKRP L276I model at comparable ages. These models emphasize the importance of FKRP in maintaining proper glycosylation of α-dystroglycan. The mild progression in the homozygous FKRP L276I model resembles that in patients with LGMD2I who are homozygous for the L276I mutation. This animal model could, therefore, be relevant for understanding the pathophysiology of and developing a treatment strategy for the human disorder. PMID:26574668

  6. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  7. Mycobacterium ulcerans Fails to Infect through Skin Abrasions in a Guinea Pig Infection Model: Implications for Transmission

    PubMed Central

    Williamson, Heather R.; Mosi, Lydia; Donnell, Robert; Aqqad, Maha; Merritt, Richard W.; Small, Pamela L. C.

    2014-01-01

    Transmission of M. ulcerans, the etiological agent of Buruli ulcer, from the environment to humans remains an enigma despite decades of research. Major transmission hypotheses propose 1) that M. ulcerans is acquired through an insect bite or 2) that bacteria enter an existing wound through exposure to a contaminated environment. In studies reported here, a guinea pig infection model was developed to determine whether Buruli ulcer could be produced through passive inoculation of M. ulcerans onto a superficial abrasion. The choice of an abrasion model was based on the fact that most bacterial pathogens infecting the skin are able to infect an open lesion, and that abrasions are extremely common in children. Our studies show that after a 90d infection period, an ulcer was present at intra-dermal injection sites of all seven animals infected, whereas topical application of M. ulcerans failed to establish an infection. Mycobacterium ulcerans was cultured from all injection sites whereas infected abrasion sites healed and were culture negative. A 14d experiment was conducted to determine how long organisms persisted after inoculation. Mycobacterium ulcerans was isolated from abrasions at one hour and 24 hours post infection, but cultures from later time points were negative. Abrasion sites were qPCR positive up to seven days post infection, but negative at later timepoints. In contrast, M. ulcerans DNA was detected at intra-dermal injection sites throughout the study. M. ulcerans was cultured from injection sites at each time point. These results suggest that injection of M. ulcerans into the skin greatly facilitates infection and lends support for the role of an invertebrate vector or other route of entry such as a puncture wound or deep laceration where bacteria would be contained within the lesion. Infection through passive inoculation into an existing abrasion appears a less likely route of entry. PMID:24722416

  8. Antibodies to Lytic Infection Proteins in Lymphocryptovirus-Infected Rhesus Macaques: a Model for Humoral Immune Responses to Epstein-Barr Virus Infection

    PubMed Central

    Orlova, Nina; Fogg, Mark H.; Carville, Angela; Wang, Fred

    2011-01-01

    Humoral immune responses to rhesus lymphocryptovirus (rhLCV) lytic infection proteins were evaluated in the rhesus macaque animal model for Epstein-Barr virus (EBV) infection. We found a hierarchy of humoral responses to 14 rhLCV lytic infection proteins in naturally infected rhesus macaques, with (i) widespread and robust responses to four glycoproteins expressed as late proteins, (ii) frequent but less robust responses to a subset of early proteins, and (iii) low-level responses to immediate-early proteins. This hierarchy of humoral responses was similar to that reported for EBV-infected humans, with the notable exception of the response to rhBARF1. Serum antibodies to rhBARF1 were frequently detected in healthy rhLCV-infected macaques, but in humans, anti-BARF1 antibodies have been reported primarily in patients with EBV-positive nasopharyngeal carcinoma (NPC). The macaque data accurately predicted that serum antibodies against BARF1 are a normal response to EBV infection when human serum samples are analyzed. The rhesus macaque animal provides a unique perspective on humoral responses to EBV infection in humans and can be a valuable model for EBV vaccine development. PMID:21734064

  9. Mathematical Model for an Effective Management of HIV Infection

    PubMed Central

    Oukouomi Noutchie, Suares Clovis

    2016-01-01

    Human immunodeficiency virus infection destroys the body immune system, increases the risk of certain pathologies, damages body organs such as the brain, kidney, and heart, and causes death. Unfortunately, this infectious disease currently has no cure; however, there are effective retroviral drugs for improving the patients' health conditions but excessive use of these drugs is not without harmful side effects. This study presents a mathematical model with two control variables, where the uninfected CD4+T cells follow the logistic growth function and the incidence term is saturated with free virions. We use the efficacy of drug therapies to block the infection of new cells and prevent the production of new free virions. Our aim is to apply optimal control approach to maximize the concentration of uninfected CD4+T cells in the body by using minimum drug therapies. We establish the existence of an optimal control pair and use Pontryagin's principle to characterize the optimal levels of the two controls. The resulting optimality system is solved numerically to obtain the optimal control pair. Finally, we discuss the numerical simulation results which confirm the effectiveness of the model. PMID:27057541

  10. Mathematical Model for an Effective Management of HIV Infection.

    PubMed

    Ogunlaran, Oladotun Matthew; Oukouomi Noutchie, Suares Clovis

    2016-01-01

    Human immunodeficiency virus infection destroys the body immune system, increases the risk of certain pathologies, damages body organs such as the brain, kidney, and heart, and causes death. Unfortunately, this infectious disease currently has no cure; however, there are effective retroviral drugs for improving the patients' health conditions but excessive use of these drugs is not without harmful side effects. This study presents a mathematical model with two control variables, where the uninfected CD4(+)T cells follow the logistic growth function and the incidence term is saturated with free virions. We use the efficacy of drug therapies to block the infection of new cells and prevent the production of new free virions. Our aim is to apply optimal control approach to maximize the concentration of uninfected CD4(+)T cells in the body by using minimum drug therapies. We establish the existence of an optimal control pair and use Pontryagin's principle to characterize the optimal levels of the two controls. The resulting optimality system is solved numerically to obtain the optimal control pair. Finally, we discuss the numerical simulation results which confirm the effectiveness of the model. PMID:27057541

  11. Modeling the Dynamics of Plasmodium vivax Infection and Hypnozoite Reactivation In Vivo

    PubMed Central

    Adekunle, Adeshina I.; Pinkevych, Mykola; McGready, Rose; Luxemburger, Christine; White, Lisa J.; Nosten, François; Cromer, Deborah; Davenport, Miles P.

    2015-01-01

    The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90–96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG. PMID:25780913

  12. Screening of different stress factors and development of growth/no growth models for Zygosaccharomyces rouxii in modified Sabouraud medium, mimicking intermediate moisture foods (IMF).

    PubMed

    Vermeulen, A; Daelman, J; Van Steenkiste, J; Devlieghere, F

    2012-12-01

    The microbial stability of intermediate moisture foods (IMF) is linked with the possible growth of osmophilic yeast and xerophilic moulds. As most of these products have a long shelf life the assessment of the microbial stability is often an important hurdle in product innovation. In this study a screening of several Zygosaccharomyces rouxii strains towards individual stress factors was performed and growth/no growth models were developed, incorporating a(w), pH, acetic acid and ethanol concentrations. These stress factors are important for sweet IMF such as chocolate fillings, ganache, marzipan, etc. A comparison was made between a logistic regression model with and without the incorporation of time as an explanatory variable. Next to the model development, a screening of the effect of chemical preservatives (sorbate and benzoate) was performed, in combination with relevant stress factors within the experimental design of the model. The results of the study showed that the influence of the investigated environmental stress factors on the growth/no growth boundary of Z. rouxii is the most significant in the first 30-40 days of incubation. Incorporating time as an explanatory variable in the model had the advantage that the growth/no growth boundary could be predicted at each time between 0 and 60 days of incubation at 22 °C. However, the growth/no growth boundary enlarged significantly leading to a less accurate prediction on the growth probability of Z. rouxii. The developed models can be a useful tool for product developers of sweet IMF. Screening with chemical preservatives revealed that benzoic acid was much less active towards Z. rouxii than sorbic acid or a mixture of both acids. PMID:22986205

  13. Early Cytokine Response to Infection with Pathogenic vs Non-Pathogenic Organisms in a Mouse Model of Endodontic Infection.

    PubMed

    Matsui, Aritsune; Stephens, Danielle; Kantarci, Alpdogan; Rittling, Susan R

    2015-01-01

    Using the subcutaneous chamber model of infection, we showed previously that a mixture of four endodontic pathogens (EP: P. intermedia, F. nucleatum, S. intermedius and P. micra) are able to persist without clearance for up to seven days, while a non-pathogenic oral species, S. mitis, was substantially cleared in this time. Here we have compared the cytokine response inside the chambers against these microorganisms. A majority of cytokines tested (17/24) showed different patterns of expression. Several cytokines had a peak of expression at 2 h after infection in response to the EP, while none showed this pattern in S. mitis infections. Chemokines were uniformly present at similar or higher levels in response to S. mitis, with redundant expression of CXCR2 ligands, while several growth/survival factors were present at higher levels in EP infections. Protease activity expressed by EP may be responsible for the lower levels of some chemokines. T-cell associated cytokines were in general expressed at extremely low levels, and did not differ between the two infections. The inflammatory markers IL-6, IL-1α and IL1-β were expressed at similar levels in both infections at early times, while TNFα was preferentially present in S. mitis infections. In EP infected chambers, reciprocal changes in levels of IL-6 and IL-1α were observed at later times suggesting a switch in the inflammatory response. Analysis of the cytokine response to infection with the individual species from the EP mix suggests that P. intermedia drives this inflammatory switch. Together these results show a surprising level of divergence of the host response to pathogenic and non-pathogenic organisms associated with oral infections, and supports a dominant effect of P. intermedia in polymicrobial endodontic infections. PMID:26171605

  14. Development of a Mycoplasma gallisepticum infection model in turkeys.

    PubMed

    Wijesurendra, Dinidu S; Kanci, Anna; Tivendale, Kelly A; Bacci, Barbara; Noormohammadi, Amir H; Browning, Glenn F; Markham, Philip F

    2015-01-01

    Mycoplasma gallisepticum causes chronic respiratory disease in chickens and is also highly pathogenic in turkeys. Several live attenuated M. gallisepticum vaccines are available for prevention of disease in chickens but they are considered to be either not safe or not efficacious in turkeys. The studies presented here aimed to develop a suitable infection model in turkeys, a prerequisite for development of a vaccine against M. gallisepticum for turkeys. Two wild-type Australian M. gallisepticum strains, Ap3AS and 100809/31, were used and their capacity to induce lesions was evaluated in 5-week-old to 6-week-old turkeys exposed to aerosols of these strains. Gross air sac lesion scores in the group exposed to Ap3AS were significantly greater than those in the group exposed to 100809/31 (P < 0.05). Histological tracheal lesion scores and tracheal mucosal thicknesses were significantly greater in birds exposed to either strain than in the unexposed birds (P < 0.05), but no significant differences were observed between the two infected groups. In a subsequent experiment, 6-week-old to 7-week-old turkeys were exposed to different doses of M. gallisepticum Ap3AS. Serology and M. gallisepticum re-isolation performed 14 days after infection showed that all birds exposed to Ap3AS were positive by rapid serum agglutination and by culture. Gross air sac lesion scores in the groups exposed to the highest dose, 8.17 × 10(8) colour-changing units Ap3AS/ml, as well as a 10-fold lower dose were significantly more severe than in the uninfected control group. Lesion scores and tracheal mucosal thicknesses were significantly greater in birds exposed to Ap3AS than in the unexposed birds (P < 0.05). However, no significant differences were seen in tracheal mucosal thicknesses or lesion scores between the groups exposed to the different doses of Ap3AS. This study has established a reliable challenge model for M. gallisepticum infection in turkeys, which will be useful for evaluation of

  15. [Model index observations in SIVmac251-infected rhesus macaques].

    PubMed

    Zhang, Yu; Wang, Jing; Liu, Xiang-mei; Min, Fan-gui; Guo, Peng-jv; Huang, Ren

    2014-11-01

    In this study, five rhesus macaques were inoculated intravenously with SIVmac251 to establish a model of simian autoimmune deficiency syndrome (SAIDS). Peripheral blood samples were collected at different time points to monitor changes in the total T cell number and T lymphocyte subset. Plasma viral loads, cytokine expression levels and anti-SIV antibody levels were also assayed to acquire certain basic indexes to evaluate disease progression in the rhesus macaque SAIDS model. During the acute stage of infection, plasma viral loads reached a peak at week 1 post-inoculation and lasted for approximately 3 to 44 weeks. The CD3+ CD4+ T lymphocyte count in peripheral blood also transitorily decreased. During the same period, the level of interferon-gamma show an increasing trend, whereas IL-12 levels decreased; IL-2, IL-4, IL-10 and TNF-alpha were maintained at normal levels or could not be detected. During the asymptomatic and ARC phases, plasma viral loads persisted above 10(4) RNA copies/mL and either increased or declined during the later stages of disease; CD3+ CD4+ counts showed a steadily declining trend and the ratio of CD4 to CD8 decreased during late-stage disease. Moreover, antibodies against viral proteins were detected in the plasma and showed a significant increasing trend, while there were no apparently changes in the levels of IFN-gamma, IL-12, IL-2, IL-4, IL-10 and TNF-alpha. In conclusion, the characteristics of the SIV animal models in our study are similar to those of patients with AIDS. Therefore, the rhesus macaque SIVmac251 infection models can be applied for further studies into AIDS. PMID:25868283

  16. Models of intestinal infection by Salmonella enterica: introduction of a new neonate mouse model.

    PubMed

    Schulte, Marc; Hensel, Michael

    2016-01-01

    Salmonella enterica serovar Typhimurium is a foodborne pathogen causing inflammatory disease in the intestine following diarrhea and is responsible for thousands of deaths worldwide. Many in vitro investigations using cell culture models are available, but these do not represent the real natural environment present in the intestine of infected hosts. Several in vivo animal models have been used to study the host-pathogen interaction and to unravel the immune responses and cellular processes occurring during infection. An animal model for Salmonella-induced intestinal inflammation relies on the pretreatment of mice with streptomycin. This model is of great importance but still shows limitations to investigate the host-pathogen interaction in the small intestine in vivo. Here, we review the use of mouse models for Salmonella infections and focus on a new small animal model using 1-day-old neonate mice. The neonate model enables researchers to observe infection of both the small and large intestine, thereby offering perspectives for new experimental approaches, as well as to analyze the Salmonella-enterocyte interaction in the small intestine in vivo. PMID:27408697

  17. Models of intestinal infection by Salmonella enterica: introduction of a new neonate mouse model

    PubMed Central

    Schulte, Marc; Hensel, Michael

    2016-01-01

    Salmonella enterica serovar Typhimurium is a foodborne pathogen causing inflammatory disease in the intestine following diarrhea and is responsible for thousands of deaths worldwide. Many in vitro investigations using cell culture models are available, but these do not represent the real natural environment present in the intestine of infected hosts. Several in vivo animal models have been used to study the host-pathogen interaction and to unravel the immune responses and cellular processes occurring during infection. An animal model for Salmonella-induced intestinal inflammation relies on the pretreatment of mice with streptomycin. This model is of great importance but still shows limitations to investigate the host-pathogen interaction in the small intestine in vivo. Here, we review the use of mouse models for Salmonella infections and focus on a new small animal model using 1-day-old neonate mice. The neonate model enables researchers to observe infection of both the small and large intestine, thereby offering perspectives for new experimental approaches, as well as to analyze the Salmonella-enterocyte interaction in the small intestine in vivo. PMID:27408697

  18. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    PubMed Central

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  19. Mimicking Metastases Including Tumor Stroma: A New Technique to Generate a Three-Dimensional Colorectal Cancer Model Based on a Biological Decellularized Intestinal Scaffold.

    PubMed

    Nietzer, Sarah; Baur, Florentin; Sieber, Stefan; Hansmann, Jan; Schwarz, Thomas; Stoffer, Carolin; Häfner, Heide; Gasser, Martin; Waaga-Gasser, Ana Maria; Walles, Heike; Dandekar, Gudrun

    2016-07-01

    Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of β-catenin in a subset of cells. One central drawback of 2D cultures-especially in consideration of drug testing-is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue

  20. Mimicking Metastases Including Tumor Stroma: A New Technique to Generate a Three-Dimensional Colorectal Cancer Model Based on a Biological Decellularized Intestinal Scaffold

    PubMed Central

    Nietzer, Sarah; Baur, Florentin; Sieber, Stefan; Hansmann, Jan; Schwarz, Thomas; Stoffer, Carolin; Häfner, Heide; Gasser, Martin; Waaga-Gasser, Ana Maria; Walles, Heike

    2016-01-01

    Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of β-catenin in a subset of cells. One central drawback of 2D cultures—especially in consideration of drug testing—is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue

  1. Pleuropulmonary paragonimiasis: mimicker of tuberculosis.

    PubMed

    Lall, Mahima; Sahni, Ajay Kumar; Rajput, A K

    2013-01-01

    Infection caused by the lung fluke is endemic in north eastern parts of India. Paragonimus westermani and Paragonimus heterotremus are known to be endemic in eastern Indian states of Manipur and Nagaland. The infection is related to eating habits of the locals and is acquired by ingestion of raw, inadequately cooked crabs or crayfish containing encysted metacercariae which act as second intermediate hosts during the life cycle of the lung fluke. Diagnosis is generally delayed due to lack of suspicion and presentation similar to tuberculosis which is endemic in the population. We report pleuropulmonary paragonimiasis in a soldier from eastern India who presented with chest pain, haemoptysis, and eosinophilia. He gave history of consumption of raw crabs while on leave at his native village in Nagaland. Ova morphologically resembling Paragonimus heterotremus were detected in sputum and bronchoalveolar lavage specimen. Symptoms resolved with praziquantel treatment. PMID:23432864

  2. Zebrafish Egg Infection Model for Studying Candida albicans Adhesion Factors.

    PubMed

    Chen, Yin-Zhi; Yang, Yun-Liang; Chu, Wen-Li; You, May-Su; Lo, Hsiu-Jung

    2015-01-01

    Disseminated candidiasis is associated with 30-40% mortality in severely immunocompromised patients. Among the causal agents, Candida albicans is the dominant one. Various animal models have been developed for investigating gene functions in C. albicans. Zebrafish injection models have increasingly been applied in elucidating C. albicans pathogenesis because of the conserved immunity, prolific fecundity of the zebrafish and the low costs of care systems. In this study, we established a simple, noninvasive zebrafish egg bath infection model, defined its optimal conditions, and evaluated the model with various C. albicans mutant strains. The deletion of SAP6 did not have significant effect on the virulence. By contrast, the deletion of BCR1, CPH1, EFG1, or TEC1 significantly reduced the virulence under current conditions. Furthermore, all embryos survived when co-incubated with bcr1/bcr1, cph1/cph1 efg1/efg1, efg1/efg1, or tec1/tec1 mutant cells. The results indicated that our novel zebrafish model is time-saving and cost effective. PMID:26569623

  3. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

    PubMed

    Yiou, René; Mahrouf-Yorgov, Meriem; Trébeau, Céline; Zanaty, Marc; Lecointe, Cécile; Souktani, Richard; Zadigue, Patricia; Figeac, Florence; Rodriguez, Anne-Marie

    2016-02-01

    Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual. Stem Cells 2016;34:392-404. PMID:26439006

  4. Comparative inhibitory effects of Thymus vulgaris L. essential oil against Staphylococcus aureus, Listeria monocytogenes and mesophilic starter co-culture in cheese-mimicking models.

    PubMed

    de Carvalho, Rayssa Julliane; de Souza, Geanny Targino; Honório, Vanessa Gonçalves; de Sousa, Jossana Pereira; da Conceição, Maria Lúcia; Maganani, Marciane; de Souza, Evandro Leite

    2015-12-01

    In the present study, we assessed the effects of Thymus vulgaris L. essential oil (TVEO) on Staphylococcus aureus and Listeria monocytogenes, pathogenic bacteria frequently associated with fresh or low-ripened cheeses (e.g., Brazilian coalho cheese), and on a starter co-culture comprising Lactococcus lactis subsp. lactis and L. lactis subsp. cremoris, which are commonly used for the production of different cheeses. To measure these effects, we determined the minimum inhibitory concentration (MIC) and assessed bacterial cell viability over time in (coalho) cheese-based broth and in a semi-solid (coalho) cheese model at 10 °C. The MIC for TVEO was 2.5 μL/mL against S. aureus and L. monocytogenes, while the MIC was 1.25 μL/mL against the starter co-culture. The TVEO (5 and 2.5 μL/mL) sharply reduced the viable counts of all assayed bacteria in cheese broth over 24 h; although, at 5 μL/mL, TVEO more severely affected the viability of the starter co-culture compared with pathogenic bacteria. The addition of 1.25 μL/g of TVEO in the semi-solid cheese model did not reduce the viable counts of all assayed bacteria. At 2.5 μL/g, TVEO slightly decreased the viable counts of S. aureus, L. monocytogenes and Lactococcus spp. in the semi-solid cheese model over 72 h. The final counts of Lactococcus spp. in a semi-solid cheese model containing 2.5 μL/mL TVEO were lower than those of pathogenic bacteria under the same conditions. These results suggest that the doses of TVEO used to control pathogenic bacteria in fermented dairy products, especially in low-ripened cheeses, should be cautiously considered for potential negative effects on the growth and survival of starter cultures. PMID:26338117

  5. Tissue mimicking materials for dental ultrasound.

    PubMed

    Singh, Rahul S; Culjat, Martin O; Grundfest, Warren S; Brown, Elliott R; White, Shane N

    2008-04-01

    While acoustic tissue mimicking materials have been explored for a variety of soft and hard biological tissues, no dental hard tissue mimicking materials have been characterized. Tooth phantoms are necessary to better understand acoustic phenomenology within the tooth environment and to accelerate the advancement of dental ultrasound imaging systems. In this study, soda lime glass and dental composite were explored as surrogates for human enamel and dentin, respectively, in terms of compressional velocity, attenuation, and acoustic impedance. The results suggest that a tooth phantom consisting of glass and composite can effectively mimic the acoustic behavior of a natural human tooth. PMID:18396919

  6. Optimal Vaccination of an Endemic Model with Variable Infectivity and Infinite Delay

    NASA Astrophysics Data System (ADS)

    Zaman, Gul; Saito, Yasuhisa; Khan, Madad

    2013-11-01

    In this work, we consider a nonlinear SEIR (susceptible, exposed, infectious, and removed) endemic model, which describes the dynamics of the interaction between susceptible and infected individuals in a population. The model represents the disease evolution through a system of nonlinear differential equations with variable infectivity which determines that the infectivity of an infected individual may not be constant during the time after infection. To control the spread of infection and to find a vaccination schedule for an endemic situation, we use optimal control strategies which reduce the susceptible, exposed, and infected individuals and increase the total number of recovered individuals. In order to do this, we introduce the optimal control problem with a suitable control function using an objective functional. We first show the existence of an optimal control for the control problem and then derive the optimality system. Finally the numerical simulations of the model is identified to fit realistic measurement which shows the effectiveness of the model.

  7. Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery

    PubMed Central

    Kang, Hyun; Chung, Yoon Sang; Kim, Sang Wook; Choi, Geun Joo; Kim, Beom Gyu; Park, Suk Won; Seok, Ju Won; Hong, Joonhwa

    2015-01-01

    Objective We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. Methods A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. Results In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. Conclusions In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required. PMID:26580394

  8. A perspective on modelling hepatitis C virus infection.

    PubMed

    Guedj, J; Rong, L; Dahari, H; Perelson, A S

    2010-12-01

    By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)-based antiviral therapy, crucial parameters of the in vivo viral kinetics have been estimated, such as the rate of production and clearance of free virus, and the rate of loss of infected cells. Furthermore, by suggesting mechanisms of action for IFN and ribavirin mathematical modelling has provided a means for evaluating and optimizing treatment strategies. Here, we review recent modelling developments for understanding complex viral kinetics patterns, such as triphasic HCV RNA declines and viral rebounds observed in patients treated with pegylated interferon and ribavirin. Moreover, we discuss new modelling approaches developed to interpret the viral kinetics observed in clinical trials with direct-acting antiviral agents, which induce a rapid decline of wild-type virus but also engender a higher risk for emergence of drug-resistant variants. Lastly, as in vitro systems have allowed a better characterization of the virus lifecycle, we discuss new modelling approaches that combine the intracellular and the extracellular viral dynamics. PMID:20723038

  9. A new in vitro model using small intestinal epithelial cells to enhance infection of Cryptosporidium parvum

    EPA Science Inventory

    To better understand and study the infection of the protozoan parasite Cryptosporidium parvum, a more sensitive in vitro assay is required. In vivo, this parasite infects the epithelial cells of the microvilli layer in the small intestine. While cell infection models using colon,...

  10. Evaluating the Risks: A Bernoulli Process Model of HIV Infection and Risk Reduction.

    ERIC Educational Resources Information Center

    Pinkerton, Steven D.; Abramson, Paul R.

    1993-01-01

    A Bernoulli process model of human immunodeficiency virus (HIV) is used to evaluate infection risks associated with various sexual behaviors (condom use, abstinence, or monogamy). Results suggest that infection is best mitigated through measures that decrease infectivity, such as condom use. (SLD)