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Sample records for infection model mimicking

  1. Odontogenic infection mimicking antral polyps.

    PubMed

    Kaplowitz, G J

    1997-01-01

    Odontogenic infections can extend into the maxillary sinus and produce sinusitis that mimics other pathoses. Infection of odontogenic origin should be considered in the differential diagnosis of maxillary sinusitis. Sinusitis should be considered in the differential diagnosis of maxillary posterior teeth with acute or chronic symptoms.

  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

    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.

  5. Infection-mimicking materials to program dendritic cells in situ

    NASA Astrophysics Data System (ADS)

    Ali, Omar A.; Huebsch, Nathaniel; Cao, Lan; Dranoff, Glenn; Mooney, David J.

    2009-02-01

    Cancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body.

  6. 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

  7. Primary pulmonary botryomycosis: a bacterial lung infection mimicking lung cancer.

    PubMed

    Ariza-Prota, M A; Pando-Sandoval, A; García-Clemente, M; Jiménez, H; Álvarez-Álvarez, C; Casan-Clara, P

    2013-07-01

    Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.

  8. Primary herpes simplex virus infection mimicking cervical cancer.

    PubMed

    Tomkins, Andrew; White, Catherine; Higgins, Stephen Peter

    2015-06-02

    We report the case of an 18-year-old woman presenting with ulceration of the cervix caused by primary type 2 herpes simplex infection in the absence of skin lesions. The differential diagnosis included cervical cancer and we referred the patient for urgent colposcopy. However, laboratory tests proved the viral aetiology of the cervical ulceration and the cervix had healed completely 3 weeks later. The case highlights the need to consider herpes simplex infection in the differential diagnosis of ulceration of the cervix even when there are no cutaneous signs of herpes.

  9. Mycobacterium haemophilum infection with prominent facial manifestation mimicking leprosy.

    PubMed

    Ishii, Kentaro; Ishii, Norihisa; Nakanaga, Kazue; Nakano, Kazuaki; Saito, Ikuo; Asahina, Akihiko

    2015-10-01

    Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69-year-old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking "facies leontina" appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases. PMID:26017241

  10. A case of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection.

    PubMed

    Das, Joyutpal; Layton, Benjamin; Lamb, Harriet; Sinnott, Nicola; Leahy, Bernard C

    2015-11-01

    Serratia marcescens is a saprophytic gram-negative bacillus capable of causing a wide range of infections. A 57-year-old female was admitted to our hospital for four weeks with community acquired pneumonia. A chest x-ray, six weeks after discharge, demonstrated multiple, bilateral 'cannon ball'-like opacities and mediastinal lymphadenopathy which were highly suspicious of disseminated malignancy or tuberculosis. The only symptom that this patient had was a productive cough. She had multiple commodities, but no specific immunodeficiency disorder. Interestingly, her sputum and bronchial washing samples grew S. marcescens. The computed tomography-guided lung biopsy demonstrated necrotic granulomatous changes. There was no pathological evidence of tuberculosis or fungal infection, malignancy or vasculitis. There are only a handful of reported cases of Serratia granulomas. Thus, we are reporting a rare instance of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    2016-05-01

    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

  17. Metastatic Calcinosis of Aortic Valve Secondary to Renal Failure Mimicking Infective Endocarditis

    PubMed Central

    Khan, Masroor A.; Chardon, Guillermo Juan Morell

    2016-01-01

    End stage renal disease has a list of consequences, cardiovascular being the most common. Inefficient dialysis can cause significant deposition of calcium all over the body, including heart valves making heart function impaired. We illustrate a case of 38-year-old female with end stage renal disease on peritoneal dialysis. The patient had been complaining of pain and swelling of the right hand for the last few months and had been seen by hand surgeon and was admitted electively for the biopsy of hand lesions. Before her planned surgery, she developed severe shortness of breath. Urgent echocardiogram revealed severe aortic regurgitation and large vegetation on the aortic valve. Infective endocarditis was suspected but blood cultures were negative for any microorganism and the patient did not meet the Duke criteria. Because of her hemodynamic instability immediate mechanical valve replacement surgery was performed. The pathology report showed extensive calcification and myxoid degeneration. No infectious agent was found. Later on, biopsy of her hand lesions showed extensive calcification with macrophages and giant cells. No atypia or malignancy was identified. This is a rare case of the metastatic calcinosis of aortic valve secondary to renal failure mimicking aortic valve infective endocarditis. PMID:27738529

  18. Increased FDG uptake of the bone marrow mimicking malignancy in a patient of eosinophilia secondary to Sparganum mansoni infection.

    PubMed

    Dong, Aisheng; Wang, Yang; Gao, Lei; Zuo, Changjing

    2014-07-01

    Secondary eosinophilia is usually associated with parasitosis in Third World countries. We present a case of eosinophilia secondary to Sparganum mansoni infection showing multifocal FDG uptake in the axial bones mimicking malignancy. Bone marrow aspirations and biopsy revealed remarkable proliferation of eosinophils which may be related to the increased FDG uptake. This case indicates that secondary eosinophilia associated with parasitosis may be one cause of diffuse FDG uptake in the bone marrow.

  19. Infection-mimicking poly(γ-glutamic acid) as adjuvant material for effective anti-tumor immune response.

    PubMed

    Seth, Anushree; Heo, Min Beom; Sung, Moon Hee; Lim, Yong Taik

    2015-04-01

    Bio-derived low molecular weight poly(γ-glutamic acid) (γ-PGA) was suggested as a novel adjuvant material for use in cancer vaccines. When the infection-mimicking γ-PGA was immunized with ovalbumin (OVA) as a model antigen, increase in the dendritic cell (DC)-mediated functions such as activation, maturation, antigen uptake, migration to lymph nodes, and priming of lymphocytes, which included cross-presentation, was observed. These DC-mediated functions were found to be facilitated by γ-PGA in a dose-dependent manner, with stimulation of toll-like receptor 4 (TLR4) being one of the underlying mechanisms. The in vivo efficacy of γ-PGA was tested in a mouse tumor model where both arms of adaptive immunity (humoral and cell-mediated) were found to be significantly enhanced in the presence of γ-PGA, indicating efficient priming of B and T cells. Moreover, immunization of mice with γ-PGA followed by EG7-OVA tumor challenge led to dramatic inhibition of tumor growth. After 71 days, the cured mice were rechallenged with tumor cells at a distant site in order to test the memory effect. No tumor growth was observed, which indicates the presence of a systemic, long-lasting immune response. Based on these results, low molecular weight γ-PGA is expected to have tremendous potential for applications in cancer immunotherapy.

  20. 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

  1. (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

  2. 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

  3. 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

  4. Deriving a blood-mimicking fluid for particle image velocimetry in Sylgard-184 vascular models.

    PubMed

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

    2009-01-01

    A new blood-mimicking fluid (BMF) has been developed for particle image velocimetry (PIV), which enables flow studies in vascular models (phantoms). A major difficulty in PIV that affects measurement accuracy is the refraction and distortion of light passing through the interface between the model and the fluid, due to the difference in refractive index (n) between the two materials. The problem can be eliminated by using a fluid with a refractive index matching that of the model. Such fluids are not commonly available, especially for vascular research where the fluid should also have a viscosity similar to human blood. In this work, a blood-mimicking fluid, composed of water (47.38% by weight), glycerol (36.94% by weight) and sodium iodide salt (15.68% by weight), was developed for compatibility with our silicone (Sylgard 184; n = 1.414) phantoms. The fluid exhibits a dynamic viscosity of 4.31+/-0.03 cP which lies within the range of human blood viscosity (4.4+/-0.6 cP). Both refractive index and viscosity were attained at 22.2+/-0.2 degrees C, which is a feasible room temperature, thus eliminating the need for a temperature-control system. The fluid will be used to study hemodynamics in vascular flow models fabricated from Sylgard 184.

  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. 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.

  8. 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

  9. Vaccination with viral protein-mimicking peptides postpones mortality in domestic pigs infected by African swine fever virus.

    PubMed

    Ivanov, Vadim; Efremov, Evgeniy E; Novikov, Boris V; Balyshev, Vladimir M; Tsibanov, Sodnom Zh; Kalinovsky, Tatiana; Kolbasov, Denis V; Niedzwiecki, Aleksandra; Rath, Matthias

    2011-01-01

    Periodic outbreaks of African swine fever virus (ASFV) infection around the world threaten local populations of domestic pigs with lethal disease and provide grounds for pandemic spread. Effective vaccination may bring this threat under control. We investigated the effectiveness of select peptides mimicking viral proteins in establishing a protective immune response. Forty-six synthetic peptides based on the analysis of the complete nucleotide sequence of ASFV were tested for immunogenicity in mice. The 17 best immune response-inducing peptide candidates were selected for further investigation. Twenty-four domestic pigs, 3-4 months old and weighing 20-25 kg, were divided into six groups (n = 4) and immunized by subcutaneous injection using a standard three-round injection protocol with one of four peptide combinations prepared from the 17 peptides (Groups 1-4) or with carrier only (Group 5). Group 6, the control, was not vaccinated. Animal body temperature and behavior were monitored during and post immunization for health assessment. Two weeks after the last round of immunizations, the pigs were infected with live ASFV (Espania 70) at 6.0 Ig GAE50/cm3, and the survival rate was monitored. Blood samples were collected for analysis the day before infection and on days 3, 7 and 10 post-infection, or from deceased animals. The serum titers of specific immunoglobulins against synthetic peptides and whole inactivated ASFV were determined by enzyme immunoassay before and after infection. The presence of viral DNA in blood serum samples was determined by polymerase chain reaction. Viral infection activity in blood sera was determined by heme absorption in cultured porcine bone marrow and porcine leukocyte cells. Repeating the injection of synthetic peptides in both the mice and pigs produced an immune response specific to individual peptides, which differed widely in the intensity scale. Specific anti-whole virus immunoglobulin binding activity in the swine serum samples

  10. Nodular Erythema Elevatum Diutinum Mimicking Kaposi's Sarcoma in a Human Immunodeficiency Virus Infected Patient

    PubMed Central

    Rao, G Raghurama; Joshi, Rajiv; Phaneendra Prasad, A Krishna; Amareswar, A; Sandhya, S; Sridevi, M

    2014-01-01

    Erythema elevatum diutinum (EED) has been emerging as a specific Human Immunodeficiency Virus (HIV) associated dermatosis in recent times. It is an extremely rare chronic disease of unknown origin and part of the spectrum of leukocytoclastic vasculitis. We describe a case of EED simulating Kaposi's sarcoma in a 52-year-old HIV infected female patient with no previous opportunistic infections and CD4+ count of 164/mm3. Therapy with oral dapsone (100 mg/day) for two weeks resulted in resolution of some lesions. PMID:25484391

  11. Legionella jordanis in hematopoietic SCT patients radiographically mimicking invasive mold infection.

    PubMed

    Meyer, R; Rappo, U; Glickman, M; Seo, S K; Sepkowitz, K; Eagan, J; Small, T N

    2011-08-01

    Opportunistic pulmonary infections are a major cause of post-transplant morbidity and mortality. Among these infections, Aspergillus is a common cause of fatal pneumonia. Owing to the precarious clinical condition of many patients who acquire invasive mold infections, clinicians often treat them on the basis of radiographic findings, such as the halo sign. However, in patients who do not respond to treatment or who have uncommon presentations, bronchoscopy or lung biopsy looking for other pathogens should be considered. This study describes two cases in which the radiographic halo signs characteristic of Aspergillus were in fact due to Legionella jordanis, a pathogen that has been culture proven only in two patients previously (both of whom had underlying lung pathology) and diagnosed by serologic evidence in several other patients. In immunocompromised patients, Legionella can present as a cavitary lesion. Thus, presumptive treatment for this organism should be considered in post-transplant patients who do not have a classic presentation for invasive fungal infection and/or who fail to respond to conventional treatment. These cases illustrate the importance of obtaining tissue cultures to differentiate among the wide variety of pathogens present in this patient population. PMID:21572462

  12. Chronic Trichuris trichiura Infection Presenting as Ileocecal Valve Swelling Mimicking Malignancy.

    PubMed

    Tuan Sharif, Sharifah Emilia; Ewe Seng, Ch'ng; Mustaffa, Nazri; Mohd Shah, Nurul Azira; Mohamed, Zeehaida

    2011-01-01

    A 46-year-old man presented with a history of passing bright red blood per rectum over the last one month. He also had on and off diarrhea with visible mucus in the stool for two months' duration. Further history was unremarkable, and physical examination revealed hemorrhoids which were subsequently banded. A colonoscopy was arranged in view of the prolonged diarrhea whereby an edematous and swollen ileocecal valve was seen. This was shown to be due to Trichuris trichiura infection, confirmed on histopathological examination of biopsies taken from the site. The patient was started on oral albendazole treatment and has been asymptomatic on latest followup. This case illustrates an accidental finding of T. trichuria infection on colonoscopic examination, which was done to investigate the patient's prolonged diarrhea.

  13. Nocardia brasiliensis infection mimicking juvenile idiopathic arthritis in a 4-year-old girl.

    PubMed

    Kapur, Nitin; Adib, Navid; Grimwood, Keith

    2013-11-01

    Nocardia are ubiquitous environmental saprophytes that cause pneumonia and disseminated disease in immunocompromised patients. They can also cause localized cutaneous and soft tissue infections in healthy people after direct percutaneous inoculation. Nocardia arthritis is rare in both forms of the disease. Here we present the first published case of a child with septic arthritis caused by N brasiliensis. Importantly, this otherwise well 4-year-old girl had no known history of trauma but presented with transient cutaneous lesions and a 6-week history of arthritis involving the right fourth digit proximal interphalangeal joint without accompanying fever or raised systemic inflammatory markers. She received a diagnosis of juvenile idiopathic arthritis and underwent antiinflammatory and immunosuppressant therapy. After 2 months she developed frank septic arthritis, which necessitated a surgical joint washout, from which an intraoperative swab grew N brasiliensis. The patient received 6 months of high-dose trimethoprim-sulfamethoxazole and remains well more than 4 years after treatment. This unusual case highlights the importance of considering an indolent infection from slow-growing organisms, including Nocardia, when diagnosing the oligoarthritis subtype of juvenile idiopathic arthritis. This is especially relevant when a single joint is involved and response to antiinflammatory therapy is suboptimal because antiinflammatory agents may mask evolving signs of infection.

  14. 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.

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

    PubMed

    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

  16. 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

  17. A case of Fasciola hepatica infection mimicking cholangiocarcinoma and ITS-1 sequencing of the worm.

    PubMed

    Kang, Bong Kyun; Jung, Bong-Kwang; Lee, Yoon Suk; Hwang, In Kyeom; Lim, Hyemi; Cho, Jaeeun; Hwang, Jin-Hyeok; Chai, Jong-Yil

    2014-04-01

    Fascioliasis is a zoonotic infection caused by Fasciola hepatica or Fasciola gigantica. We report an 87-year-old Korean male patient with postprandial abdominal pain and discomfort due to F. hepatica infection who was diagnosed and managed by endoscopic retrograde cholangiopancreatography (ERCP) with extraction of 2 worms. At his first visit to the hospital, a gallbladder stone was suspected. CT and magnetic retrograde cholangiopancreatography (MRCP) showed an intraductal mass in the common bile duct (CBD) without proximal duct dilatation. Based on radiological findings, the presumed diagnosis was intraductal cholangiocarcinoma. However, in ERCP which was performed for biliary decompression and tissue diagnosis, movable materials were detected in the CBD. Using a basket, 2 living leaf-like parasites were removed. The worms were morphologically compatible with F. hepatica. To rule out the possibility of the worms to be another morphologically close species, in particular F. gigantica, 1 specimen was processed for genetic analysis of its ITS-1 region. The results showed that the present worms were genetically identical (100%) with F. hepatica but different from F. gigantica.

  18. Infection by Panton-Valentine leukocidin-producing Staphylococcus aureus clinically mimicking Lemierre's syndrome.

    PubMed

    Shivashankar, Girish H; Murukesh, Nishanth; Varma, M P S; Sharif, Ikram M; Glynn, Gerard

    2008-01-01

    Lemierre's syndrome is an oropharyngeal infection which leads to severe septic thrombophlebitis of the internal jugular vein and metastatic abscesses of the lungs and other organs. It is usually caused by Fusobacterium necrophorum, a Gram-negative obligate anaerobe. An unusual case of Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus infection masquerading as Lemierre's syndrome is reported here. A 32-year-old fit and otherwise healthy male presented on Christmas morning with a boil on his left cheek for 2 days and generalized rash for 3 h. His general condition began to worsen, he developed facial swelling and loss of vision in the left eye and was transferred to the intensive care unit. His treatment was taken over by team of specialists and further investigations revealed thrombophlebitis of the left internal jugular vein and cavernous sinus thrombosis with multiple brain infarcts and lung abscesses. His condition remained critical with multiple cranial nerve involvement despite being on broad-spectrum antibiotics. Blood cultures grew S. aureus which was producing PVL toxin. He improved gradually over several weeks. He underwent intensive physiotherapy and made a good recovery. Although a rare entity, it is important to consider Lemierre's syndrome in septic patients who present with rapidly worsening symptoms.

  19. Sporadic Burkitt Lymphoma Mimicking Osteomyelitis of the Mandible Revealing Clinically Unsuspected HIV Infection.

    PubMed

    Sivolella, Stefano; Rizzo, Giovanni; Valente, Marialuisa; Lumachi, Franco

    2015-09-01

    Adult sporadic Burkitt lymphoma is a rare and highly aggressive malignancy, accounting for approximately 1-2% of adult lymphomas in Western countries, and exclusively intra-oral localization is very uncommon. We describe a rare case of a moderately painful sporadic Burkitt lymphoma localized in the posterior third of the left mandibular bone, initially misdiagnosed as osteomyelitis-like lesion, in a patient Epstein-Barr virus infection-negative with unknown human immunodeficiency virus (HIV) positivity and acquired immunodeficiency syndrome. A 52-year-old man was referred to our Department complaining of persistent moderate pain localized in the left mandibular arch. According to clinical and radiological features, a diagnosis of post-extraction osteomyelitis was made and a surgical revision, including soft and hard tissue biopsy, was performed. Histopathology revealed the presence of a diffuse proliferation of lymphoid cells, exhibiting the typical 'starry-sky' appearance that was consistent with the diagnosis of B-type non-Hodgkin lymphoma. Unexpectedly, HIV seropositivity was also found, but the patient was unaware of this, and the history did not reveal any particular risk factor for HIV infection. Positron-emission tomography showed a highly (18)F-fluorodeoxyglucose-avid mass in the left maxillofacial region and extensive disease in bone marrow and mediastinum. Thus, the patient was referred to our onco-hematological team for final assessment and care. In conclusion, sporadic Burkitt lymphoma is an aggressive malignancy, which rarely affects adults with initial intra-oral manifestations. In the presence of abnormal gingival or alveolar lesions, a non-odontogenic disease should be suspected and the appropriate diagnostic test should be performed.

  20. Calea zacatechichi dichloromethane extract exhibits antidiarrheal and antinociceptive effects in mouse models mimicking irritable bowel syndrome.

    PubMed

    Sałaga, M; Kowalczuk, A; Zielinska, M; Błażewicz, A; Fichna, J

    2015-10-01

    Calea zacatechichi Schltdl. (Asteraceae alt. Compositae) is a Mexican plant commonly used in folk medicine to treat respiratory and gastrointestinal (GI) disorders. The objective of this study is to characterize the effect of C. zacatechichi extracts in mouse models mimicking the symptoms of irritable bowel syndrome (IBS). Powdered C. zacatechichi herb (leaves, stems, and flowers) was extracted with methanol. Methanolic extract was filtered and evaporated giving methanolic fraction. The residue was extracted with dichloromethane (DCM). Methanolic and DCM (200 mg/kg, per os) extracts were screened for their effect on GI motility in several in vitro tests, and the antidiarrheal and antinociceptive effects were assessed using mouse models. The influence of the DCM extract on motoric parameters and exploratory behaviors was also assessed. Finally, the composition of C. zacatechichi DCM extract was qualitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) method. C. zacatechichi DCM extract significantly inhibited the contractility of mouse colon in vitro (IC50 = 17 ± 2 μg/ml). Administration of the DCM extract in vivo (200 mg/kg, per os) significantly prolonged the time of whole GI transit (46 ± 1 vs. 117 ± 27 min for control and DCM-treated animals, respectively; P = 0.0023), inhibited hypermotility, and reduced pain in mouse models mimicking functional GI disorders. Our findings suggest that constituents of the C. zacatechichi DCM extract exhibit antidiarrheal and analgesic activity. The extract may thus become an attractive material for isolation of compounds that may be used as a supplementary treatment for pain and diarrhea associated with IBS in the future. PMID:26068703

  1. 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.

  2. 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

  3. MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.

    PubMed

    Kossivas, Fotis; Angeli, S; Kafouris, D; Patrickios, C S; Tzagarakis, V; Constantinides, C

    2012-06-01

    three-dimensional tissue-mimicking models of cardiac anatomy from 2D MR images using rapid prototyping manufacturing processes was developed. For synthesized elastomers, doping strategies with two different concentrations of the MRI contrast agent Dotarem allowed independent and concurrent control of the imaging characteristics (contrast and relaxivity) during the synthetic process for increased contrast agent absorption, with tremendous potential for non-destructive in vivo use and applications to cardiovascular and cerebrovascular diseases.

  4. 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.

  5. Animal infection models and ethics -- the perfect infection model.

    PubMed

    Zak, Oto; O'Reilly, Terence

    1993-05-01

    Experimental infection models have long been recognized as an essential part of testing anti-infective therapies. A perfect animal model would be a model that satisfied not only scientific criteria, but ethical criteria as well. In the design and execution of such experiments, scientific and ethical considerations are not mutually exclusive, but should be convergent and therefore result in the optimal model.

  6. 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

  7. 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.

  8. Artificial Klebsiella pneumoniae biofilm model mimicking in vivo system: altered morphological characteristics and antibiotic resistance.

    PubMed

    Singla, Saloni; Harjai, Kusum; Chhibber, Sanjay

    2014-04-01

    The purpose of this study was to develop a biofilm model of Klebsiella pneumoniae B5055, mimicking in vivo biofilm system so as to determine susceptibility of different phases of biofilm to antibiotics by three-dimensional analysis. Artificial mature biofilm of K. pneumoniae was made on black, polycarbonate membranes. Biofilm structure was visualized by scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM). Viable count method, CLSM and SEM analysis confirmed that mature, uniform and viable biofilms can be formed on the polycarbonate membranes by this method. The three-dimensional heterogeneity of biofilm was confirmed on the basis of results of CLSM, which is an important characteristics of in vivo biofilm system. Staining with the LIVE/DEAD BacLight viability kit and acridine orange suggested that the center of biofilm had more inactive cells compared with actively dividing cells on the periphery. Amikacin at a concentration of 40 μg ml⁻¹ was effective against younger biofilm whereas ineffective against older biofilm that showed sparsely populated dead cells using the BacLight viability staining kit. Role of altered morphological characteristics toward increased antibiotic susceptibility was also studied for different phases of K. pneumoniae biofilm by CLSM and light microscopy. Thickness of biofilm increased from 0.093 to 0.231 mm with time. So, both heterogeneity and thickness of the biofilm are likely to influence the ineffectiveness of amikacin in older biofilm. The present model holds considerable clinical relevance and may be useful for evaluating the efficacy of antimicrobial agent on bacterial biofilms in vitro.

  9. Interaction of fengycin with stratum corneum mimicking model membranes: a calorimetry study.

    PubMed

    Eeman, Marc; Olofsson, Gerd; Sparr, Emma; Nasir, Mehmet Nail; Nylander, Tommy; Deleu, Magali

    2014-09-01

    Based on its outstanding antifungal properties, it is reasonable to believe that fengycin might be efficient to topically treat localized dermatomycoses. Since most of the fungi species involved in the formation of those mycotic skin diseases colonize primarily the stratum corneum (SC), studying the interaction between fengycin and SC-mimicking lipid membranes is a primary step to determine the potential of fengycin to overcome the physical barrier of the skin. In this respect, multilamellar lipid vesicles (MLVs), with a lipid composition mimicking that of the SC, were prepared and characterized by differential scanning calorimetry (DSC). The critical micelle concentration (CMC) of fengycin was also assessed under skin conditions and found to be 1.2±0.1μM. The molecular interactions of fengycin with SC-mimicking MLVs were investigated by both DSC and isothermal titration calorimetry (ITC). Results showed that the interactions were considerably affected by changes in lipid phase behaviour. At 40°C and below, fengycin induced exothermic changes in the lipid structures suggesting that less-ordered lipid domains became more-ordered in presence of fengycin. At 60°C, clearly endothermic interaction enthalpies were observed, which could arise from the "melting" of remaining solid domains enriched in high melting lipids that without fengycin melt at higher temperatures.

  10. Dirofilariasis Mimicking an Acute Scrotum.

    PubMed

    Bertozzi, Mirko; Rinaldi, Victoria Elisa; Prestipino, Marco; Giovenali, Paolo; Appignani, Antonino

    2015-10-01

    Human infections caused by Dirofilaria repens have been reported in many areas of the world. We describe a case of a 3-year-old child with an intrascrotal mass caused by D repens mimicking an acute scrotum. This represents the first case of scrotal dirofilariasis described in pediatric age with such an unusual presentation.

  11. 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

  12. Fatal bacillary angiomatosis mimicking an infiltrative vascular tumour in the immune restoration phase of an HIV-infected patient.

    PubMed

    Murillo, Oscar; Mimbrera, Daniel; Petit, Ana; Gil, Horacio; Anda, Pedro; Carrera, Marta; Podzamczer, Daniel

    2012-01-01

    Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.

  13. Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections

    PubMed Central

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

    2013-01-01

    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 Th1 and Th17 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

  14. 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.

  15. Methylesterase behaviour is related to polysaccharide organisation in model systems mimicking cell walls.

    PubMed

    Bonnin, Estelle; Mutic, Jelena; Nikolic, Jasna; Burr, Sally; Robert, Paul; Crépeau, Marie-Jeanne

    2015-06-25

    Pectin gels and pectin-cellulose binary gels were used as cell wall-mimicking systems to investigate the diffusion ability of a fungal pectin methylesterase. Increasing content of cellulose in the gel appears to result: (i) in longer demethylated blocks thus favouring AaPME processivity, and (ii) in accelerated enzyme kinetics. To better understand this unexpected behaviour, a method was set up to investigate the gel porosity as a function of the cellulose content by following the passive diffusion of three pullulans having different hydrodynamic volumes. Like the enzyme, the pullulans diffused more efficiently in the gels containing the highest proportions of cellulose. Altogether, these results suggest that the gel settled differently during formation according to the respective proportions of the two polysaccharides. With cellulose present, a fraction of pectin would form close interactions with the microfibrils resulting in a larger volume accessible to diffusing molecules. This volume would be related to the cellulose concentration. PMID:25839794

  16. 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

  17. Burn-induced subepicardial injury in frog heart: a simple model mimicking ST segment changes in ischemic heart disease

    PubMed Central

    KAZAMA, Itsuro

    2015-01-01

    To mimic ischemic heart disease in humans, several animal models have been created, mainly in rodents by surgically ligating their coronary arteries. In the present study, by simply inducing burn injuries on the bullfrog heart, we reproduced abnormal ST segment changes in the electrocardiogram (ECG), mimicking those observed in ischemic heart disease, such as acute myocardial infarction and angina pectoris. The “currents of injury” created by a voltage gradient between the intact and damaged areas of the myocardium, negatively deflected the ECG vector during the diastolic phase, making the ST segment appear elevated during the systolic phase. This frog model of heart injury would be suitable to explain the mechanisms of ST segment changes observed in ischemic heart disease. PMID:26346747

  18. 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.

  19. 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.

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

    PubMed Central

    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

  1. 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

  2. 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.

  3. Insulin-Mimicking Bioactivities of Acylated Inositol Glycans in Several Mouse Models of Diabetes with or without Obesity

    PubMed Central

    Suzuki, Susumu; Suzuki, Chitose; Hinokio, Yoshinori; Ishigaki, Yasushi; Katagiri, Hideki; Kanzaki, Makoto; Azev, Viatcheslav N.; Chakraborty, Nilanjana; d'Alarcao, Marc

    2014-01-01

    Insulin-mimetic species of low molecular weight are speculated to mediate some intracellular insulin actions. These inositol glycans, which are generated upon insulin stimulation from glycosylphosphatidylinositols, might control the activity of a multitude of insulin effector enzymes. Acylated inositol glycans (AIGs) are generated by cleavage of protein-free GPI precursors through the action of GPI-specific phospholipase C (GPI-PLC) and D (GPI-PLD). We synthesized AIGs (IG-1, IG-2, IG-13, IG-14, and IG-15) and then evaluated their insulin-mimicking bioactivities. IG-1 significantly stimulated glycogen synthesis and lipogenesis in 3T3-L1 adipocytes and rat isolated adipocytes dose-dependently. IG-2 significantly stimulated lipogenesis in rat isolated adipocytes dose-dependently. IG-15 also enhanced glycogen synthesis and lipogenesis in 3T3-L1 adipocytes. The administration of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with normal diets. The administration of IG-1 decreased plasma glucose in STZ-diabetic C57B6N mice. The treatment of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with high fat-diets and db/db mice. The long-term treatment of IG-1 decreased plasma glucose and reduced food intake and body weight in C57B6N mice with high fat-diets and ob/ob mice. Thus, IG-1 has insulin-mimicking bioactivities and improves glucose tolerance in mice models of diabetes with or without obesity. PMID:24971987

  4. Insulin-mimicking bioactivities of acylated inositol glycans in several mouse models of diabetes with or without obesity.

    PubMed

    Suzuki, Susumu; Suzuki, Chitose; Hinokio, Yoshinori; Ishigaki, Yasushi; Katagiri, Hideki; Kanzaki, Makoto; Azev, Viatcheslav N; Chakraborty, Nilanjana; d'Alarcao, Marc

    2014-01-01

    Insulin-mimetic species of low molecular weight are speculated to mediate some intracellular insulin actions. These inositol glycans, which are generated upon insulin stimulation from glycosylphosphatidylinositols, might control the activity of a multitude of insulin effector enzymes. Acylated inositol glycans (AIGs) are generated by cleavage of protein-free GPI precursors through the action of GPI-specific phospholipase C (GPI-PLC) and D (GPI-PLD). We synthesized AIGs (IG-1, IG-2, IG-13, IG-14, and IG-15) and then evaluated their insulin-mimicking bioactivities. IG-1 significantly stimulated glycogen synthesis and lipogenesis in 3T3-L1 adipocytes and rat isolated adipocytes dose-dependently. IG-2 significantly stimulated lipogenesis in rat isolated adipocytes dose-dependently. IG-15 also enhanced glycogen synthesis and lipogenesis in 3T3-L1 adipocytes. The administration of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with normal diets. The administration of IG-1 decreased plasma glucose in STZ-diabetic C57B6N mice. The treatment of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with high fat-diets and db/db mice. The long-term treatment of IG-1 decreased plasma glucose and reduced food intake and body weight in C57B6N mice with high fat-diets and ob/ob mice. Thus, IG-1 has insulin-mimicking bioactivities and improves glucose tolerance in mice models of diabetes with or without obesity.

  5. 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

    2016-04-28

    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] (1) closely mimicking the structure of the native OEC was obtained. In this study, we extensively examined the geometric, electronic and spin structures of 1 using the density functional theory method. Our results showed that the geometric structure of 1 can be accurately reproduced by theoretical calculations, and revealed many similarities in the ground valence and spin states between 1 and the native OEC. We also revealed two different valence states in the one-electron oxidized state of 1 (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 1 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 1. 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 1.

  6. Models of dengue virus infection.

    PubMed

    Bente, Dennis A; Rico-Hesse, Rebeca

    2006-01-01

    The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models. PMID:18087566

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity.

    PubMed

    Gürcan, Önder; Türker, Kemal S; Mano, Jean-Pierre; Bernon, Carole; Dikenelli, Oğuz; Glize, Pierre

    2014-04-01

    We present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments.

  12. Lessons learned from mice and man: mimicking human allergy through mouse models.

    PubMed

    Graham, Michelle T; Nadeau, Kari C

    2014-11-01

    The relevance of using mouse models to represent human allergic pathologies is still unclear. Recent studies suggest the limitations of using models as a standard for assessing immune response and tolerance mechanisms, as mouse models often do not sufficiently depict human atopic conditions. Allergy is a combination of aberrant responses to innocuous environmental agents and the subsequent TH2-mediated inflammatory responses. In this review, we will discuss current paradigms of allergy - specifically, TH2-mediated and IgE-associated immune responses - and current mouse models used to recreate these TH2-mediated pathologies. Our overall goal is to highlight discrepancies that exist between mice and men by examining the advantages and disadvantages of allergic mouse models with respect to the human allergic condition.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD.

    PubMed

    Solinas, Paola; Isola, Michela; Lilliu, Maria Alberta; Conti, Gabriele; Civolani, Alberto; Demelia, Luigi; Loy, Francesco; Isola, Raffaella

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that includes a wide spectrum of morphological alterations. In research, animal models are crucial in evaluating not only the pathogenesis of NAFLD and its progression, but also the therapeutic effects of various agents. Investigations on the ultrastructural features of NAFLD in humans are not copious, due to the difficulty to obtain human samples and to the long time of NAFLD to evolve. Translational comparative studies on the reliability of animal models in representing the histopathologic picture as seen in humans are missing. To overcome this lack of investigations, we compared the ultrastructural NAFLD features of an animal model versus human. Sprague-Dawley rats were fed with a high fat diet (HFD) for 1-4 weeks, while control rats were fed with a standard diet. Human specimens were collected from patients with diagnosed fatty liver disease, undergoing liver biopsies or surgery. Rat and human samples were examined by light microscopy and by transmission and high resolution scanning electron microscopy. The present work demonstrated that NAFLD in animal model and in human, share overlapping ultrastructural features. In conclusion, animal HFD represent an appropriate tool in studying the pathogenesis of NAFLD.

  18. Murine models of vaginal trichomonad infections.

    PubMed

    Cobo, Eduardo R; Eckmann, Lars; Corbeil, Lynette B

    2011-10-01

    Trichomonas vaginalis and Tritrichomonas foetus cause common sexually transmitted infections in humans and cattle, respectively. Mouse models of trichomoniasis are important for pathogenic and therapeutic studies. Here, we compared murine genital infections with T. vaginalis and T. foetus. Persistent vaginal infection with T. foetus was established with 100 parasites but T. vaginalis infection required doses of 10(6), perhaps because of greater susceptibility to killing by mouse vaginal polymorphonuclear leukocytes. Infection with T. vaginalis persisted longest after combined treatment of mice with estrogen and dexamethasone, whereas infection was only short-lived when mice were given estrogen or dexamethasone alone, co-infected with Lactobacillus acidophilus, and/or pretreated with antibiotics. Infection rates were similar with metronidazole-resistant (MR) and metronidazole-sensitive (MS) T. vaginalis. High dose but not low dose metronidazole treatment controlled infection with MS better than MR T. vaginalis. These murine models will be valuable for investigating the pathogenesis and treatment of trichomoniasis. PMID:21976570

  19. Blunt cavernous nerve injury: A new animal model mimicking postradical prostatectomy neurogenic impotence.

    PubMed

    Karakiewicz, P I; Bazinet, M; Zvara, P; Begin, L R; Brock, G B

    1996-01-01

    Our goal was to develop an animal model of cavernous nerve injury similar to that encountered among patients having undergone a successful nerve sparing radical prostatectomy and to compare patterns of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining to quality of erections using the newly developed model. We studied 50 mature Sprague Dawley rats, which were divided into five equal groups. Animals were either observed (sham), underwent an exploratory laparotomy, underwent moderate or severe percussive injury to both cavernous nerves, or underwent ablation of both cavernous nerves. Between 28 and 30 days later, all animals underwent electrostimulation and simultaneous recording of intracavernosal pressure. After sacrifice, penes were harvested and penile tissue NADPH-diaphorase staining pattern was assessed. Severity of cavernous nerve percussive injury and NADPH-diaphorase staining patterns correlated with the quality of recorded erections. This model is a useful experimental tool for research in the field of erectile dysfunction such as is encountered following a successful nerve sparing radical prostatectomy. Penile biopsy assessing NADPH-diaphorase staining may potentially prove to be a useful minimally-invasive diagnostic modality quantifying neurogenic erectile function among patients following radical prostatectomy. PMID:21224162

  20. Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

    PubMed Central

    Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka; Schierwagen, Robert; Uschner, Frank Erhard; Strassburg, Christian P.; Fischer, Hans-Peter; Spengler, Ulrich; Trebicka, Jonel

    2016-01-01

    Background Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared it to human NCIPH. Methods Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one week after last embolization), hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in patients with NCIPH. Results Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. Discussion This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies. PMID:27589391

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

    PubMed Central

    Pas, Suzan D.; van der Net, Guido; de Man, Robert A.; Osterhaus, Albert D. M. E.; Haagmans, Bart L.; Boonstra, Andre

    2016-01-01

    and antiviral drugs. We compared the in vivo infectivity of clinical samples from chronic HEV patients in human liver chimeric mice to an in vitro virus culture system. Efficient in vivo HEV infection is observed after inoculation with feces- and liver-derived HEV but not with HEV RNA-containing plasma or cell culture supernatant. HEV in chimeric mice is preferentially shed toward bile and feces, mimicking the HEV infection course in humans. The observed in vivo infectivity differences may be relevant for the epidemiology of HEV in humans. This novel small-animal model therefore offers new avenues to unravel HEV's pathobiology. PMID:26889028

  8. Ebola virus infection modeling and identifiability problems

    PubMed Central

    Nguyen, Van Kinh; Binder, Sebastian C.; Boianelli, Alessandro; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection. PMID:25914675

  9. 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

  10. Animal models of orthopedic implant infection.

    PubMed

    An, Y H; Friedman, R J

    1998-01-01

    Prosthetic infection following total joint replacement can have catastrophic results both physically and psychologically for patients, leading to complete failure of the arthroplasty, possible amputation, prolonged hospitalization, and even death. Although with the use of prophylactic antibiotics and greatly improved operating room techniques the infection rate has decreased markedly during the years, challenges still remain for better preventive and therapeutic measures. In this review the in vivo experimental methods for studies of prosthetic infection are discussed, concentrating on (1) the animal models that have been established and the use of these animal models for studies of pathogenesis of bacteria, behavior of biofilm, effect of biomaterials on prosthetic infection rate, and the effect of infection on biomaterial surfaces, and (2) how to design and conduct an animal model of orthopedic prosthetic infection including animal selection, implant fabrication, bacterial inoculation, surgical technique, and the methods for evaluating the results.

  11. Modeling cytomegalovirus infection in mouse tumor models.

    PubMed

    Price, Richard Lee; Chiocca, Ennio Antonio

    2015-01-01

    The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving. Originally discovered in glioblastoma in 2002, the number of cancers, where intratumoral CMV antigen is detected, has increased in recent years suggesting that CMV actively affects the pathobiology of certain tumors. These findings are controversial as several groups have also reported inability to replicate these results. Regardless, several clinical trials for glioblastoma are underway or have been completed that target intratumoral CMV with anti-viral drugs or immunotherapy. Therefore, a better understanding of the possible pathobiology of CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and orthotopic malignant glioma mouse models to study the role of CMV in cancer development and progression. These models recapitulate for the most part intratumoral CMV expression as seen in human tumors. Additionally, we discovered that CMV infection in Trp53(-/+) mice promotes pleomorphic rhabdomyosarcomas. These mouse models are not only a vehicle for studying pathobiology of the viral-tumor interaction but also a platform for developing and testing cancer therapeutics. PMID:25853089

  12. 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

  13. 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

  14. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    PubMed

    Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

    2010-01-01

    The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  15. 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

  16. Zebrafish embryo model of Bartonella henselae infection.

    PubMed

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

    2014-10-01

    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.

  17. 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

  18. 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

  19. Isolated giant molluscum contagiosum mimicking epidermoid cyst.

    PubMed

    Uzuncakmak, Tugba K; Kuru, Burce C; Zemheri, Ebru I; Zindanci, Ilkin; Turkoglu, Zafer; Kavala, Mukaddes

    2016-07-01

    Molluscum contagiosum is a benign cutaneous viral infection which is caused by double- stranded DNA poxvirus. It affects mainly children and young adults and usually presents with single or multiple umblicated papules or nodules on face, arms, legs and anogenital regions. It may present in atypical size and clinical appearance in patients with altered or impaired immunity and rarely in immuncompetent patients. Herein we present an immuncompetent young adult patient with isolated giant molluscum contagiosum, which was mimicking epidermoid cyst clinically. PMID:27648389

  20. Isolated giant molluscum contagiosum mimicking epidermoid cyst

    PubMed Central

    Uzuncakmak, Tugba K.; Kuru, Burce C.; Zemheri, Ebru I.; Zindanci, Ilkin; Turkoglu, Zafer; Kavala, Mukaddes

    2016-01-01

    Molluscum contagiosum is a benign cutaneous viral infection which is caused by double- stranded DNA poxvirus. It affects mainly children and young adults and usually presents with single or multiple umblicated papules or nodules on face, arms, legs and anogenital regions. It may present in atypical size and clinical appearance in patients with altered or impaired immunity and rarely in immuncompetent patients. Herein we present an immuncompetent young adult patient with isolated giant molluscum contagiosum, which was mimicking epidermoid cyst clinically. PMID:27648389

  1. Isolated giant molluscum contagiosum mimicking epidermoid cyst

    PubMed Central

    Uzuncakmak, Tugba K.; Kuru, Burce C.; Zemheri, Ebru I.; Zindanci, Ilkin; Turkoglu, Zafer; Kavala, Mukaddes

    2016-01-01

    Molluscum contagiosum is a benign cutaneous viral infection which is caused by double- stranded DNA poxvirus. It affects mainly children and young adults and usually presents with single or multiple umblicated papules or nodules on face, arms, legs and anogenital regions. It may present in atypical size and clinical appearance in patients with altered or impaired immunity and rarely in immuncompetent patients. Herein we present an immuncompetent young adult patient with isolated giant molluscum contagiosum, which was mimicking epidermoid cyst clinically.

  2. 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

  3. 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.

  4. Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

    PubMed

    Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

    2016-01-01

    The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue.

  5. 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

  6. 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).

  7. 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

  8. Dynamics of the evolution of Batesian mimicry: molecular phylogenetic analysis of ant-mimicking Myrmarachne (Araneae: Salticidae) species and their ant models.

    PubMed

    Ceccarelli, F S; Crozier, R H

    2007-01-01

    Batesian mimicry is seen as an example of evolution by natural selection, with predation as the main driving force. The mimic is under selective pressure to resemble its model, whereas it is disadvantageous for the model to be associated with the palatable mimic. In consequence one might expect there to be an evolutionary arms race, similar to the one involving host-parasite coevolution. In this study, the evolutionary dynamics of a Batesian mimicry system of model ants and ant-mimicking salticids is investigated by comparing the phylogenies of the two groups. Although Batesian mimics are expected to coevolve with their models, we found the phylogenetic patterns of the models and the mimics to be indicative of adaptive radiation by the mimic rather than co-speciation between the mimic and the model. This shows that there is strong selection pressure on Myrmarachne, leading to a high degree of polymorphism. There is also evidence of sympatric speciation in Myrmarachne, the reproductive isolation possibly driven by female mate choice in polymorphic species.

  9. 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.

  10. Zebrafish: modeling for herpes simplex virus infections.

    PubMed

    Antoine, Thessicar Evadney; Jones, Kevin S; Dale, Rodney M; Shukla, Deepak; Tiwari, Vaibhav

    2014-02-01

    For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

  11. 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

  12. Epidemiological models of Mycobacterium tuberculosis complex infections.

    PubMed

    Ozcaglar, Cagri; Shabbeer, Amina; Vandenberg, Scott L; Yener, Bülent; Bennett, Kristin P

    2012-04-01

    The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted using simulations of epidemiological models. This study provides a review of earlier study on modeling different aspects of tuberculosis dynamics. The models simulate tuberculosis transmission dynamics, treatment, drug resistance, control strategies for increasing compliance to treatment, HIV/TB co-infection, and patient groups. The models are based on various mathematical systems, such as systems of ordinary differential equations, simulation models, and Markov Chain Monte Carlo methods. The inferences from the models are justified by case studies and statistical analysis of TB patient datasets. PMID:22387570

  13. 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

  14. Hosting Infection: Experimental Models to Assay Candida Virulence

    PubMed Central

    MacCallum, Donna M.

    2012-01-01

    Although normally commensals in humans, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei are capable of causing opportunistic infections in individuals with altered physiological and/or immunological responses. These fungal species are linked with a variety of infections, including oral, vaginal, gastrointestinal, and systemic infections, with C. albicans the major cause of infection. To assess the ability of different Candida species and strains to cause infection and disease requires the use of experimental infection models. This paper discusses the mucosal and systemic models of infection available to assay Candida virulence and gives examples of some of the knowledge that has been gained to date from these models. PMID:22235206

  15. 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

  16. 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

  17. Periocular dirofilariasis mimicking lacrimal sac mucocoele.

    PubMed

    Pauly, Marian; Biswas, Jyotirmay; Hussain, Rameez N; Anantharaman, Giridhar

    2013-10-01

    Dirofilariasis is a zoonotic infection caused by filarial nematodes belonging to the genus dirofilariae. Dirofilaria is commonly seen in dogs, cats and other carnivorous animals world wide. Mosquitoes of the genus Culex, Anopheles and Aedes are the vectors and the humans are either incidental hosts or dead-end hosts. It affects lungs, liver and other visceral organs. Ocular involvement is rarely been reported. We present a case of 51-year-old female from Kerala, the southern State of India presented with a mass mimicking lacrimal sac mucocoele whose biopsy is proved to be dirofilariasis.

  18. 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.

  19. 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.

  20. Fuzzy Modeling and Control of HIV Infection

    PubMed Central

    Zarei, Hassan; Kamyad, Ali Vahidian; Heydari, Ali Akbar

    2012-01-01

    The present study proposes a fuzzy mathematical model of HIV infection consisting of a linear fuzzy differential equations (FDEs) system describing the ambiguous immune cells level and the viral load which are due to the intrinsic fuzziness of the immune system's strength in HIV-infected patients. The immune cells in question are considered CD4+ T-cells and cytotoxic T-lymphocytes (CTLs). The dynamic behavior of the immune cells level and the viral load within the three groups of patients with weak, moderate, and strong immune systems are analyzed and compared. Moreover, the approximate explicit solutions of the proposed model are derived using a fitting-based method. In particular, a fuzzy control function indicating the drug dosage is incorporated into the proposed model and a fuzzy optimal control problem (FOCP) minimizing both the viral load and the drug costs is constructed. An optimality condition is achieved as a fuzzy boundary value problem (FBVP). In addition, the optimal fuzzy control function is completely characterized and a numerical solution for the optimality system is computed. PMID:22536298

  1. An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier.

    PubMed

    Lehmann, Andrea D; Daum, Nicole; Bur, Michael; Lehr, Claus-Michael; Gehr, Peter; Rothen-Rutishauser, Barbara M

    2011-04-01

    A triple cell co-culture model was recently established by the authors, consisting of either A549 or 16HBE14o- epithelial cells, human blood monocyte-derived macrophages and dendritic cells, which offers the possibility to study the interaction of xenobiotics with those cells. The 16HBE14o- containing co-culture model mimics the airway epithelial barrier, whereas the A549 co-cultures mimic the alveolar type II-like epithelial barrier. The goal of the present work was to establish a new triple cell co-culture model composed of primary alveolar type I-like cells isolated from human lung biopsies (hAEpC) representing a more realistic alveolar epithelial barrier wall, since type I epithelial cells cover >93% of the alveolar surface. Monocultures of A549 and 16HBE14o- were morphologically and functionally compared with the hAEpC using laser scanning microscopy, as well as transmission electron microscopy, and by determining the epithelial integrity. The triple cell co-cultures were characterized using the same methods. It could be shown that the epithelial integrity of hAEpC (mean ± SD, 1180 ± 188 Ω cm(2)) was higher than in A549 (172 ± 59 Ω cm(2)) but similar to 16HBE14o- cells (1469 ± 156 Ω cm(2)). The triple cell co-culture model with hAEpC (1113 ± 30 Ω cm(2)) showed the highest integrity compared to the ones with A549 (93 ± 14 Ω cm(2)) and 16HBE14o- (558 ± 267 Ω cm(2)). The tight junction protein zonula occludens-1 in hAEpC and 16HBE14o- were more regularly expressed but not in A549. The epithelial alveolar model with hAEpC combined with two immune cells (i.e. macrophages and dendritic cells) will offer a novel and more realistic cell co-culture system to study possible cell interactions of inhaled xenobiotics and their toxic potential on the human alveolar type I epithelial wall.

  2. 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

  3. Mimicking human texture classification

    NASA Astrophysics Data System (ADS)

    van Rikxoort, Eva M.; van den Broek, Egon L.; Schouten, Theo E.

    2005-03-01

    In an attempt to mimic human (colorful) texture classification by a clustering algorithm three lines of research have been encountered, in which as test set 180 texture images (both their color and gray-scale equivalent) were drawn from the OuTex and VisTex databases. First, a k-means algorithm was applied with three feature vectors, based on color/gray values, four texture features, and their combination. Second, 18 participants clustered the images using a newly developed card sorting program. The mutual agreement between the participants was 57% and 56% and between the algorithm and the participants it was 47% and 45%, for respectively color and gray-scale texture images. Third, in a benchmark, 30 participants judged the algorithms' clusters with gray-scale textures as more homogeneous then those with colored textures. However, a high interpersonal variability was present for both the color and the gray-scale clusters. So, despite the promising results, it is questionable whether average human texture classification can be mimicked (if it exists at all).

  4. Xanthomatous pleuritis mimicking mesothelioma.

    PubMed

    McGuire, Franklin R; Gourdin, Todd; Finley, James L; Downie, Gordon

    2009-01-01

    Recurrent non-malignant exudative effusions remain a diagnostic and potentially management dilemma. Fluid characteristics frequently narrow the differential but fail to offer a definitive diagnosis. Medical thoracoscopy is well tolerated and allows direct visualization and biopsy of pleural processes under conscious sedation. Rarely, macroscopic appearance and even histology may be misleading. We present a case of xanthomatous pleuritis that mimicked early mesothelioma. Our patient was a 69-year-old female with a large left pleural effusion. Her medical history was significant for a recent small pericardial effusion without cardiac dysfunction. Thoracentesis revealed a non-malignant exudative effusion. Thoracoscopy demonstrated two foci of raised soft plaques with petechial hemorrhage and adhesions. Preliminary evaluation suggested chronic inflammation admixed with proliferating spindle cells and necrosis. The immunohistochemical phenotype of the spindle cells favored a spindle and epithelioid cell neoplasm, mesothelioma. Because of discord between pathologists, we repeated the thoracoscopy through the existing chest tube/thoracoscopy site. We acquired more tissue for special stains and outside review. Following extensive immunohistochemistry, the diagnosis of xanthomatous pleuritis was made. Our patient quickly recovered with steroid therapy and is without recurrence 18 months later. This case demonstrates the utility and nuances of medical thoracoscopy in a perplexing case of xanthomatous pleuritis. PMID:18223309

  5. 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

  6. 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.

  7. Influence of Antarctic Ice Sheet Lowering on the Southern Hemisphere Climate: Model Experiments Mimicking the Mid-Miocene

    NASA Astrophysics Data System (ADS)

    Justino, Flavio; Stordal, Frode

    2013-04-01

    Conditions in Antarctica have varied substantially in the Earth's climate history. During the early Miocene (23-17 Ma), as suggested by records from the Ocean Drilling Program (ODP) Sites 1090 and 1218, the ice volume was approximately 50%-125% of its present-day values. It has been argued that the rapid Cenozoic glaciation of Antarctica was induced by a decline in atmospheric CO2 from 4 times to 2 times preindustrial atmospheric level over a 10-Myr period. Minor contributions to this glaciation have also been associated with the opening of Southern Ocean gateways between Antarctica and the Australia-Tasmanian Passage, and Antarctica and the South America-Drake Passage, although it has been argued that the total amount of water owing in the Drake passage during the Eocene/Oligocene boundary may have been insufficient for reducing the poleward heat transport. The AIS is responsible for the greater amount of reflected solar radiation in the SH, and has significantly influenced meridional circulation due to its role in the characterization of the latitudinal thermal gradient. Moreover significant interaction between the polar and tropical regions through the link between the ENSO and West Antarctica has been demonstrated. It has been suggested that warming episodes during the Miocene were closely related to small changes in the Southern Ocean's freshwater balance. Paleorecords (ODP Sites 1090 and 1218) have also been utilized to disentangle the nature of deep-sea water mass. The analyses have demonstrated that warmer bottom water coexisted with increased production of Antarctic Bottom Water during the Plio-Pleistocene (1.6Ma) compared to today. We have investigated impacts of changes to the AIS topography on the climate system by using a coupled climate model, an Earth Model of Intermediate Complexity (EMIC), namely Speedy-Ocean (SPEEDO). We have designed experiments to inter-compare the nature of the atmospheric and oceanic circulation under modern conditions and

  8. Discrete virus infection model of hepatitis B virus.

    PubMed

    Zhang, Pengfei; Min, Lequan; Pian, Jianwei

    2015-01-01

    In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al's virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E1 and E2, represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R0<1 then the virus free equilibrium E1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data.

  9. 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

  10. 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

  11. 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

  12. Pulmonary "cyclosporinoma" mimicking infection after heart transplantation.

    PubMed

    Gould, K; Freeman, R; Odom, N J; Locke, T J; McGregor, C G

    1987-01-01

    Tissue from a transthoracic needle biopsy, which was performed as part of the investigation of an undiagnosed left upper lobe opacity in a patient after orthotopic heart transplantation, revealed numerous macrophages loaded with oil globules. No causative organisms were present. High-pressure liquid chromatography showed a similar profile to the oil in which cyclosporine is suspended. The lesion appears to have been caused by aspiration of cyclosporine.

  13. Global stability of infection-free state and endemic infection state of a modified human immunodeficiency virus infection model.

    PubMed

    Sun, Qilin; Min, Lequan; Kuang, Yang

    2015-06-01

    This study proposes a modified human immunodeficiency virus (HIV) infection differential equation model with a saturated infection rate. This model has an infection-free equilibrium point and an endemic infection equilibrium point. Using Lyapunov functions and LaSalle's invariance principle shows that if the model's basic reproductive number R0 < 1, the infection-free equilibrium point is globally asymptotically stable, otherwise the endemic infection equilibrium point is globally asymptotically stable. It is shown that a forward bifurcation will occur when R0 = 1. The basic reproductive number R0 of the modified model is independent of plasma total CD4⁺ T cell counts and thus the modified model is more reasonable than the original model proposed by Buonomo and Vargas-De-León. Based on the clinical data from HIV drug resistance database of Stanford University, using the proposed model simulates the dynamics of two group patients' anti-HIV infection treatments. The simulation results have shown that the first 4 weeks' treatments made the two group patients' R'0 < 1, respectively. After the period, drug resistance made the two group patients' R'0 > 1. The results explain why the two group patients' mean CD4⁺ T cell counts raised and mean HIV RNA levels declined in the first period, but contrary in the following weeks.

  14. 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

  15. 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

  16. 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

  17. An integrated stewardship model: antimicrobial, infection prevention and diagnostic (AID).

    PubMed

    Dik, Jan-Willem H; Poelman, Randy; Friedrich, Alexander W; Panday, Prashant Nannan; Lo-Ten-Foe, Jerome R; van Assen, Sander; van Gemert-Pijnen, Julia E W C; Niesters, Hubert G M; Hendrix, Ron; Sinha, Bhanu

    2016-01-01

    Considering the threat of antimicrobial resistance and the difficulties it entails in treating infections, it is necessary to cross borders and approach infection management in an integrated, multidisciplinary manner. We propose the antimicrobial, infection prevention and diagnostic stewardship model comprising three intertwined programs: antimicrobial, infection prevention and diagnostic stewardship, involving all stakeholders. The focus is a so-called 'theragnostics' approach. This leads to a personalized infection management plan, improving patient care and minimizing resistance development. Furthermore, it is important that healthcare regions nationally and internationally work together, ensuring that the patient (and microorganism) transfers will not cause problems in a neighboring institution. This antimicrobial, infection prevention and diagnostic stewardship model can serve as a blue print to implement innovative, integrative infection management.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Disseminated sporotrichosis mimicking sarcoidosis.

    PubMed

    Yang, Deborah J; Krishnan, Ravi S; Guillen, David R; Schmiege, Lorenz M; Leis, Paula F; Hsu, Sylvia

    2006-04-01

    A 40-year-old Caucasian man presented to the dermatology clinic at Baylor College of Medicine, Houston, Texas, in February 2003, for the evaluation of three nonhealing ulcers. The patient's past medical history was significant for hypothyroidism and pulmonary sarcoidosis, the diagnosis of which was made in June 2000. In March 2000, the patient had complained of cough and shortness of breath. A purified protein derivative (PPD) (Mantoux text) was negative. Computed tomography (CT) scans of the chest revealed diffuse hilar and mediastinal adenopathy and bilateral interstitial and alveolar infiltrates. Although consistent with sarcoidosis, these findings were insufficient to exclude other etiologies, including disseminated fungal infection. Cultures and stains of subsequent bronchoscopy specimens failed to reveal any organisms, and histopathologic evaluation of the specimens was nondiagnostic. Based on the imaging studies and the negative cultures, a diagnosis of sarcoidosis was made, and the patient was started on therapy with prednisone. Before coming to our clinic, the patient had been on several courses of prednisone. In May 2002, the patient had presented to a private dermatologist with a 1-year history of a nonhealing 2.4 cm x 2.0 cm ulcer on the left medial forearm. Two biopsies were reported as nondiagnostic. The patient's presentation was interpreted as most consistent with Mycobacterium marinum infection, and so he was empirically treated with minocycline. This treatment was continued for almost 3 months without improvement in the ulcer. A few months after the minocycline had been discontinued, the patient was treated empirically for 2 months with ciprofloxacin. This treatment was also unsuccessful in ameliorating the ulcer. In between the two courses of antibiotics, specimens from the lesion were sent for bacterial and fungal cultures, which revealed normal skin flora. In January 2003, the patient returned to his private dermatologist with three ulcerations

  3. 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.

  4. 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

  5. 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

  6. A probability cellular automaton model for hepatitis B viral infections.

    PubMed

    Xiao, Xuan; Shao, Shi-Huang; Chou, Kuo-Chen

    2006-04-01

    The existing models of hepatitis B virus (HBV) infection dynamics are based on the assumption that the populations of viruses and cells are uniformly mixed. However, the real virus infection system is actually not homogeneous and some spatial factors might play a nontrivial role in governing the development of HBV infection and its outcome. For instance, the localized populations of dead cells might adversely affect the spread of infection. To consider this kind of inhomogeneous feature, a simple 2D (dimensional) probability Cellular Automaton model was introduced to study the dynamic process of HBV infection. The model took into account the existence of different types of HBV infectious and non-infectious particles. The simulation results thus obtained showed that the Cellular Automaton model could successfully account for some important features of the disease, such as its wide variety in manifestation and its age dependency. Meanwhile, the effects of the model's parameters on the dynamical process of the infection were also investigated. It is anticipated that the Cellular Automaton model may be extended to serve as a useful vehicle for studying, among many other complicated dynamic biological systems, various persistent infections with replicating parasites.

  7. 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

  8. 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.

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

    PubMed

    Pilloux, Ludovic; LeRoy, Didier; Brunel, Christophe; Roger, Thierry; Greub, Gilbert

    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

  10. 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

  11. 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.

  12. Mathematical analysis of a tuberculosis model with differential infectivity

    NASA Astrophysics Data System (ADS)

    Bowong, Samuel; Tewa, Jean Jules

    2009-11-01

    This paper deals with the global properties of a tuberculosis model with mass action incidence and two differential infectivity. The direct Lyapunov method enables us to prove that the considered model is globally stable: There is always a globally asymptotically stable equilibrium state. Depending on the value of the basic reproduction number R0 , this state can be either endemic (R0 > 1), or infection-free (R0 ⩽ 1). Numerical results are provided to illustrate analytical results.

  13. Paracoccidioidomycosis Mimicking Sarcoidosis: A Review of 8 Cases.

    PubMed

    Coelho, Mariana Guimarães; Severo, Cecília Bittencourt; de Mattos Oliveira, Flávio; Hochhegger, Bruno; Severo, Luiz Carlos

    2016-02-01

    Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with this disease. The diagnosis is based on exhaustive exclusion of differential diagnoses, particularly granulomatous infections. We report data on eight patients with paracoccidioidomycosis mimicking sarcoidosis. Five patients presented with a chronic pulmonary type infection and three had a disseminated form after immunosuppressive treatment. The mycological diagnosis in noncaseating granulomas is emphasized and reviewed.

  14. Modeling inoculum dose dependent patterns of acute virus infections.

    PubMed

    Li, Yan; Handel, Andreas

    2014-04-21

    Inoculum dose, i.e. the number of pathogens at the beginning of an infection, often affects key aspects of pathogen and immune response dynamics. These in turn determine clinically relevant outcomes, such as morbidity and mortality. Despite the general recognition that inoculum dose is an important component of infection outcomes, we currently do not understand its impact in much detail. This study is intended to start filling this knowledge gap by analyzing inoculum dependent patterns of viral load dynamics in acute infections. Using experimental data for adenovirus and infectious bronchitis virus infections as examples, we demonstrate inoculum dose dependent patterns of virus dynamics. We analyze the data with the help of mathematical models to investigate what mechanisms can reproduce the patterns observed in experimental data. We find that models including components of both the innate and adaptive immune response are needed to reproduce the patterns found in the data. We further analyze which types of innate or adaptive immune response models agree with observed data. One interesting finding is that only models for the adaptive immune response that contain growth terms partially independent of viral load can properly reproduce observed patterns. This agrees with the idea that an antigen-independent, programmed response is part of the adaptive response. Our analysis provides useful insights into the types of model structures that are required to properly reproduce observed virus dynamics for varying inoculum doses. We suggest that such models should be taken as basis for future models of acute viral infections.

  15. 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.

  16. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.

  17. Berloque dermatitis mimicking child abuse.

    PubMed

    Gruson, Lisa Moed; Chang, Mary Wu

    2002-11-01

    Berloque dermatitis is a type of photocontact dermatitis. It occurs after perfumed products containing bergamot (or a psoralen) are applied to the skin followed by exposure to sunlight. Striking linear patterns of hyperpigmentation are characteristic, corresponding to local application of the scented product. In the acute phase, erythema and even blistering can be seen. We report a case of berloque dermatitis in a 9-year-old girl that was initially reported as child abuse. To our knowledge, this is the first report of berloque dermatitis mimicking child abuse. Questioning to elicit a history of perfume application coupled with sunlight exposure should help to prevent this misdiagnosis in children.

  18. 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.

  19. 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.

  20. 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.

  1. [Animal models for the study of Helicobacter pylori infection].

    PubMed

    Miszczyk, Eliza; Walencka, Maria; Mikołajczyk-Chmiela, Magdalena

    2014-05-15

    The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural history of H. pylori infection. Preclinical investigations on animal models are an essential stage of research which enrich the knowledge on treatment and prevention strategies.

  2. Mouse models of dengue virus infection for vaccine testing.

    PubMed

    Sarathy, Vanessa V; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-12-10

    Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple

  3. Mouse models of dengue virus infection for vaccine testing.

    PubMed

    Sarathy, Vanessa V; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-12-10

    Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple

  4. Trichuris muris: a model of gastrointestinal parasite infection.

    PubMed

    Klementowicz, Joanna E; Travis, Mark A; Grencis, Richard K

    2012-11-01

    Infection with soil-transmitted gastrointestinal parasites, such as Trichuris trichiura, affects more than a billion people worldwide, causing significant morbidity and health problems especially in poverty-stricken developing countries. Despite extensive research, the role of the immune system in triggering parasite expulsion is incompletely understood which hinders the development of anti-parasite therapies. Trichuris muris infection in mice serves as a useful model of T. trichiura infection in humans and has proven to be an invaluable tool in increasing our understanding of the role of the immune system in promoting either susceptibility or resistance to infection. The old paradigm of a susceptibility-associated Th1 versus a resistance-associated Th2-type response has been supplemented in recent years with cell populations such as novel innate lymphoid cells, basophils, dendritic cells and regulatory T cells proposed to play an active role in responses to T. muris infection. Moreover, new immune-controlled mechanisms of expulsion, such as increased epithelial cell turnover and mucin secretion, have been described in recent years increasing the number of possible targets for anti-parasite therapies. In this review, we give a comprehensive overview of experimental work conducted on the T. muris infection model, focusing on important findings and the most recent reports on the role of the immune system in parasite expulsion.

  5. Animal models of enteroaggregative Escherichia coli infection

    PubMed Central

    Philipson, Casandra W.; Bassaganya-Riera, Josep; Hontecillas, Raquel

    2013-01-01

    Enteroaggregative Escherichia coli (EAEC) has been acknowledged as an emerging cause of gastroenteritis worldwide for over two decades. Epidemiologists are revealing the role of EAEC in diarrheal outbreaks as a more common occurrence than ever suggested before. EAEC induced diarrhea is most commonly associated with travelers, children and immunocompromised individuals however its afflictions are not limited to any particular demographic. Many attributes have been discovered and characterized surrounding the capability of EAEC to provoke a potent pro-inflammatory immune response, however cellular and molecular mechanisms underlying initiation, progression and outcomes are largely unknown. This limited understanding can be attributed to heterogeneity in strains and the lack of adequate animal models. This review aims to summarize current knowledge about EAEC etiology, pathogenesis and clinical manifestation. Additionally, current animal models and their limitations will be discussed along with the value of applying systems-wide approaches such as computational modeling to study host-EAEC interactions. PMID:23680797

  6. 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.

  7. Modeling malaria and typhoid fever co-infection dynamics.

    PubMed

    Mutua, Jones M; Wang, Feng-Bin; Vaidya, Naveen K

    2015-06-01

    Malaria and typhoid are among the most endemic diseases, and thus, of major public health concerns in tropical developing countries. In addition to true co-infection of malaria and typhoid, false diagnoses due to similar signs and symptoms and false positive results in testing methods, leading to improper controls, are the major challenges on managing these diseases. In this study, we develop novel mathematical models describing the co-infection dynamics of malaria and typhoid. Through mathematical analyses of our models, we identify distinct features of typhoid and malaria infection dynamics as well as relationships associated to their co-infection. The global dynamics of typhoid can be determined by a single threshold (the typhoid basic reproduction number, R0(T)) while two thresholds (the malaria basic reproduction number, R0(M), and the extinction index, R0(MM)) are needed to determine the global dynamics of malaria. We demonstrate that by using efficient simultaneous prevention programs, the co-infection basic reproduction number, R0, can be brought down to below one, thereby eradicating the diseases. Using our model, we present illustrative numerical results with a case study in the Eastern Province of Kenya to quantify the possible false diagnosis resulting from this co-infection. In Kenya, despite having higher prevalence of typhoid, malaria is more problematic in terms of new infections and disease deaths. We find that false diagnosis-with higher possible cases for typhoid than malaria-cause significant devastating impacts on Kenyan societies. Our results demonstrate that both diseases need to be simultaneously managed for successful control of co-epidemics. PMID:25865934

  8. 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

  9. Achalasia mimicking prepubertal anorexia nervosa.

    PubMed

    Richterich, Andreas; Brunner, Romuald; Resch, Franz

    2003-04-01

    A 9-year-old girl presents for continuing weight loss of 10 kg over the course of 1 year. Medical history showed three episodes of pneumonia requiring hospital admission in the 6 months before presentation and 4 months of weekly psychotherapy for anorexia nervosa. A thorough history of eating behavior and a review of systems revealed not only typical aspects of prepubertal anorexia nervosa but also vomiting at night while asleep, difficulty drinking liquids, epigastric pain, and a frequent experience of "a lump in the throat"; these symptoms were not suggestive of a diagnosis of anorexia nervosa but rather of esophageal achalasia. The patient was transferred to the Department of Pediatrics, and a diagnosis of esophageal achalasia was made by chest x-ray and barium swallow. After dilatation and botulinum toxin application, the patient regained weight easily and was discharged in stable condition. In this case, esophageal achalasia mimicked prepubertal anorexia nervosa.

  10. 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

  11. 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.

  12. 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

  13. A Golden Hamster Model for Human Acute Nipah Virus Infection

    PubMed Central

    Wong, K. Thong; Grosjean, Isabelle; Brisson, Christine; Blanquier, Barissa; Fevre-Montange, Michelle; Bernard, Arlette; Loth, Philippe; Georges-Courbot, Marie-Claude; Chevallier, Michelle; Akaoka, Hideo; Marianneau, Philippe; Lam, Sai Kit; Wild, T. Fabian; Deubel, Vincent

    2003-01-01

    A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153–2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection. PMID:14578210

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Models for the study of Clostridium difficile infection.

    PubMed

    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

  20. 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

  1. Effects of infection on honey bee population dynamics: a model.

    PubMed

    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.

  2. Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient.

    PubMed

    Ruiz-Villaverde, Ricardo; Sanchez-Cano, Daniel; Martinez-Peinado, Carmen M; Galan-Gutierrez, Manuel

    2016-01-01

    Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed. PMID:27267196

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

    PubMed

    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. PMID:27630637

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

    PubMed

    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.

  5. Pyomyositis mimicking right iliac fossa mass: review of the literature.

    PubMed Central

    Iwuagwu, O. C.; Deans, G. T.

    2000-01-01

    Pyomyositis is a pyogenic infection of skeletal muscle. Its incidence in temperate countries though low is rising. Most cases from the temperate region involve immuno-compromised patients. The onset is usually insidious with progression to large purulent collections. Because of its low incidence in temperate countries, it is often initially misdiagnosed. A high index of suspicion with appropriate imaging techniques, aggressive surgical intervention and adjunctive antibiotic therapy are the keys to prompt resolution. A case of pyomyositis mimicking right iliac fossa (RIF) mass is described with a review of the literature. Images Figure 1 PMID:11041041

  6. 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.

  7. 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. PMID:27630637

  8. Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved.

    PubMed

    Ostorhazi, Eszter; Holub, Marianna Csilla; Rozgonyi, Ferenc; Harmos, Ferenc; Cassone, Marco; Wade, John D; Otvos, Laszlo

    2011-05-01

    Although the designer proline-rich antimicrobial peptide A3-APO has only modest activity against Escherichia coli and Acinetobacter baumannii in vitro, in mouse models of systemic and wound infections it shows superior efficacy compared with conventional antibiotics. In this study, the efficacy of A3-APO in several additional mouse models was investigated, including Staphylococcus aureus wound infection, mixed Klebsiella pneumoniae-A. baumannii-Proteus mirabilis wound infection and K. pneumoniae lung infection, mimicking blast wound infections, foot ulcers and ventilator-induced nosocomial infections, respectively. Whilst the peptide practically did not kill the strains in vitro, when administered intramuscularly or as an aerosol it significantly improved mouse survival and reduced bacterial counts at the infection site and in blood. In the lung infection study, the blood bacterial counts following A3-APO treatment were as low as after treatment with colistin and were lower than after treatment with imipenem or amikacin. The wounds of treated animals, unlike their untreated counterparts, lacked pus and signs of inflammation. In human peripheral blood mononuclear cells, A3-APO upregulated the expression of the anti-inflammatory cytokines interleukin-4 and interleukin-10 by four- to six-fold. One of the mechanisms mediating the in vivo protective effects might be the prevention of inflammation around bacterial infiltration.

  9. Exploration of West Nile Virus Infection in Mouse Models.

    PubMed

    Wang, Penghua

    2016-01-01

    West Nile virus (WNV) causes neurological diseases by penetrating the central nervous system (CNS)-an immune-privileged system. Although the CNS residential cells can produce antiviral immune responses, the blood leukocytes are required to contain virus spread. However, infiltrating leukocytes may also contribute to immunopathology if they overreact. Thus analyses of WNV infectivity and leukocyte numbers in the CNS are critical for understanding of WNV pathogenesis in experimental mouse models. Here I describe two basic assays for quantification of viral titers and infiltrating leukocytes in the mouse brain after WNV infection.

  10. 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

  11. Estimation of HIV infection and incubation via state space models.

    PubMed

    Tan, W Y; Ye, Z

    2000-09-01

    By using the state space model (Kalman filter model) of the HIV epidemic, in this paper we have developed a general Bayesian procedure to estimate simultaneously the HIV infection distribution, the HIV incubation distribution, the numbers of susceptible people, infective people and AIDS cases. The basic approach is to use the Gibbs sampling method combined with the weighted bootstrap method. We have applied this method to the San Francisco AIDS incidence data from January 1981 to December 1992. The results show clearly that both the probability density function of the HIV infection and the probability density function of the HIV incubation are curves with two peaks. The results of the HIV infection distribution are clearly consistent with the finding by Tan et al. [W.Y. Tan, S.C. Tang, S.R. Lee, Estimation of HIV seroconversion and effects of age in San Francisco homosexual populations, J. Appl. Stat. 25 (1998) 85]. The results of HIV incubation distribution seem to confirm the staged model used by Satten and Longini [G. Satten, I. Longini, Markov chain with measurement error: estimating the 'true' course of marker of the progression of human immunodeficiency virus disease, Appl. Stat. 45 (1996) 275]. PMID:10942785

  12. Rat indwelling urinary catheter model of Candida albicans biofilm infection.

    PubMed

    Nett, Jeniel E; Brooks, Erin G; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen; Andes, David R

    2014-12-01

    Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Infection.

    PubMed

    Miclau, Theodore; Schmidt, Andrew H; Wenke, Joseph C; Webb, Lawrence X; Harro, Janette M; Prabhakara, Ranjani; Shirtliff, Mark E

    2010-09-01

    Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections.

  18. 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

  19. 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.

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

    DOE PAGES

    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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Fibrosing mediastinitis mimicking bronchogenic carcinoma

    PubMed Central

    Bayiz, Hulya; Mutluay, Neslihan; Koyuncu, Adem; Demirag, Funda; Dagli, Gulfidan; Berktas, Bahadir; Berkoglu, Mine

    2013-01-01

    Fibrosing mediastinitis is a rare but benign disorder characterized by an excessive fibrotic reaction in the mediastinum which can result in compromise of airways, great vessels, and other mediastinal structures. In this paper we presented a patient with fibrosing mediastinitis mimicking bronchogenic carcinoma. The patient was a 32-year-old diabetic male admitting with cough and hemoptysis. There was a right hilar mass and multiple mediastinal conglomerated lymph nodes on chest computed tomography. Positron emission tomography with computed tomography (PET/CT) scan demonstrated increased fluorodeoxyglucose (FDG) uptake at the right hilar mass lesion and mediastinal lymph nodes. Fiberoptic bronchoscopy showed mucosal distortion of right upper lobe. Pathologic examination of the mucosal biopsy revealed inflammation. Endobronchial ultrasound guided transbronchial needle and cervical mediastinoscopic lymph node biopsies were undiagnostic. Diagnostic thoracotomy confirmed the diagnosis fibrosing mediastinitis. Administration of six months of systemic corticosteroid and antituberculous therapy was not beneficial. In conclusion, despite being a rare clinical entity, fibrosing mediastinitis should be kept in mind in the differential diagnosis of mediastinal mass lesions of unknown etiology. The diagnosis is exceptionally difficult in the presence of atypical radiological findings. The treatment is particularly challenging without any proven effective therapy. PMID:23372962

  6. Gel-Entrapped Staphylococcus aureus Bacteria as Models of Biofilm Infection Exhibit Growth in Dense Aggregates, Oxygen Limitation, Antibiotic Tolerance, and Heterogeneous Gene Expression.

    PubMed

    Pabst, Breana; Pitts, Betsey; Lauchnor, Ellen; Stewart, Philip S

    2016-10-01

    An experimental model that mimicked the structure and characteristics of in vivo biofilm infections, such as those occurring in the lung or in dermal wounds where no biomaterial surface is present, was developed. In these infections, microbial biofilm forms as cell aggregates interspersed in a layer of mucus or host matrix material. This structure was modeled by filling glass capillary tubes with an agarose gel that had been seeded with Staphylococcus aureus bacteria and then incubating the gel biofilm in medium for up to 30 h. Confocal microscopy showed that the bacteria formed in discrete pockets distributed throughout the gel matrix. These aggregates enlarged over time and also developed a size gradient, with the clusters being larger near the nutrient- and oxygen-supplied interface and smaller at greater depths. Bacteria entrapped in gels for 24 h grew slowly (specific growth rate, 0.06 h(-1)) and were much less susceptible to oxacillin, minocycline, or ciprofloxacin than planktonic cells. Microelectrode measurements showed that the oxygen concentration decreased with depth into the gel biofilm, falling to values less than 3% of air saturation at depths of 500 μm. An anaerobiosis-responsive green fluorescent protein reporter gene for lactate dehydrogenase was induced in the region of the gel where the measured oxygen concentrations were low, confirming biologically relevant hypoxia. These results show that the gel biofilm model captures key features of biofilm infection in mucus or compromised tissue: formation of dense, distinct aggregates, reduced specific growth rates, local hypoxia, and antibiotic tolerance. PMID:27503656

  7. Immunology of fungal infections: lessons learned from animal models.

    PubMed

    Steele, Chad; Wormley, Floyd L

    2012-08-01

    The continuing AIDS epidemic coupled with increased usage of immunosuppressive drugs to prevent organ rejection or treat autoimmune diseases has resulted in an increase in individuals at risk for acquiring fungal diseases. These concerns highlight the need to elucidate mechanisms of inducing protective immune responses against fungal pathogens. Consequently, several experimental models of human mycoses have been developed to study these diseases. The availability of transgenic animal models allows for in-depth analysis of specific components, receptors, and signaling pathways that elicit protection against fungal diseases. This review focuses on recent advances in our understanding of immune responses to fungal infections gained using animal models.

  8. Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection.

    PubMed

    Mahanty, Siddhartha; Gupta, Manisha; Paragas, Jason; Bray, Mike; Ahmed, Rafi; Rollin, Pierre E

    2003-08-01

    A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc "immune" mice rechallenged ip (10(6) PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-alpha and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-alpha and IFN-gamma were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-alpha levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-alpha, as compared with lethal ip infection. PMID:12919746

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Target cell limitation constrains chlamydial load in persistent infections: results from mathematical modelling applied to mouse genital tract infection data.

    PubMed

    Craig, Andrew P; Rank, Roger G; Bowlin, Anne K; Wand, Handan; Wilson, David P

    2015-02-01

    The interactions between chlamydial pathogens and their host contribute to the outcome of infection. Nonresolving infections in immunodeficient mice can provide insights into these mechanisms by allowing observation of a form of persistent infection. Using a mathematical model, we predict that in a nonresolving infection, the number of chlamydiae in the host will attain a stable equilibrium and that this equilibrium will be independent of the inoculum size. We test this hypothesis by infecting RAG(-/-) mice with 10(4)-10(7) inclusion-forming units (IFU) of Chlamydia muridarum and comparing the IFU levels at equilibrium. There were no statistically significant differences in equilibrium IFU levels between the reference group and other inoculation groups, supporting the hypothesis. Using the mathematical model, we estimated that at equilibrium just 3% of the chlamydiae infect a target cell. We predict that the equilibrium IFU level is highly sensitive to the rate of replenishment of healthy cells. The limitation of target cells is a key driver of infection dynamics, affecting both the peak of infection and the equilibrium level of persistent infections. Target cell limitation likely plays an important role in the dynamics of human infections as well.

  19. Animal Models of Respiratory Syncytial Virus Infection and Disease

    PubMed Central

    Sacco, Randy E.; Durbin, Russell K.; Durbin, Joan E.

    2015-01-01

    The study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. The reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. This review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and describes the advantages and disadvantages of alternative model systems. PMID:26176495

  20. Primary central nervous system lymphoma in an human immunodeficiency virus-infected patient mimicking bilateral eye sign in brain seen in fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusany; Thirugnanam, Rajasekar; Shibu, Deepu; Kalarikal, Radhakrishnan Edathurthy; Shinto, Ajit Sugunan

    2014-01-01

    Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) has proven useful in the diagnosis, staging, and detection of metastasis and posttreatment monitoring of several malignancies in human immunodeficiency virus (HIV)-infected patients. It also has the ability to make the important distinction between malignancy and infection in the evaluation of central nervous system (CNS) lesions, leading to the initiation of the appropriate treatment and precluding the need for invasive biopsy. We report an interesting case of HIV positive 35-year-old woman presented with headache, disorientation, and decreased level of consciousness. She underwent whole body PET/CT which showed multiple lesions in the cerebrum which mimics bilateral eye in brain. A diagnosis of a primary CNS lymphoma was made and patient was started on chemotherapy. PMID:24761060

  1. Primary central nervous system lymphoma in an human immunodeficiency virus-infected patient mimicking bilateral eye sign in brain seen in fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusany; Thirugnanam, Rajasekar; Shibu, Deepu; Kalarikal, Radhakrishnan Edathurthy; Shinto, Ajit Sugunan

    2014-04-01

    Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) has proven useful in the diagnosis, staging, and detection of metastasis and posttreatment monitoring of several malignancies in human immunodeficiency virus (HIV)-infected patients. It also has the ability to make the important distinction between malignancy and infection in the evaluation of central nervous system (CNS) lesions, leading to the initiation of the appropriate treatment and precluding the need for invasive biopsy. We report an interesting case of HIV positive 35-year-old woman presented with headache, disorientation, and decreased level of consciousness. She underwent whole body PET/CT which showed multiple lesions in the cerebrum which mimics bilateral eye in brain. A diagnosis of a primary CNS lymphoma was made and patient was started on chemotherapy.

  2. A mouse model for Chlamydia suis genital infection.

    PubMed

    Donati, Manuela; Di Paolo, Maria; Favaroni, Alison; Aldini, Rita; Di Francesco, Antonietta; Ostanello, Fabio; Biondi, Roberta; Cremonini, Eleonora; Ginocchietti, Laura; Cevenini, Roberto

    2015-02-01

    A mouse model for Chlamydia suis genital infection was developed. Ninety-nine mice were randomly divided into three groups and intravaginally inoculated with chlamydia: 45 mice (group 1) received C. suis purified elementary bodies (EBs), 27 (group 2) were inoculated with C. trachomatis genotype E EBs and 27 mice (group 3) with C. trachomatis genotype F EBs. Additionally, 10 mice were used as a negative control. At seven days post-infection (dpi) secretory anti-C. suis IgA were recovered from vaginal swabs of all C. suis inoculated mice. Chlamydia suis was isolated from 93, 84, 71 and 33% vaginal swabs at 3, 5, 7 and 12 dpi. Chlamydia trachomatis genotype E and F were isolated from 100% vaginal swabs up to 7 dpi and from 61 and 72%, respectively, at 12 dpi. Viable C. suis and C. trachomatis organisms were isolated from uterus and tubes up to 16 and 28 dpi, respectively. The results of the present study show the susceptibility of mice to intravaginal inoculation with C. suis. A more rapid course and resolution of C. suis infection, in comparison to C. trachomatis, was highlighted. The mouse model could be useful for comparative investigations involving C. suis and C. trachomatis species.

  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. The plaque-antiserum method: an assay of virus infectivity and an experimental model of virus infection.

    PubMed

    De Flora, S

    1974-05-01

    Areas of cytopathic effect can be circumscribed in cell monolayers by adding antiserum to the liquid nutrient medium after adsorption of virus. This procedure represents a simple and reliable tool for the titration of virus infectivity and provides an experimental model for studying some aspects of virus infection.

  5. 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

  6. 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

  7. Mimicking the effect of gravity using an elastic membrane

    NASA Astrophysics Data System (ADS)

    Wu, Yecun; Zhu, Changqing; Wang, Yijun; Shi, Qingfan

    2014-05-01

    Comparing astrospace with an elastic membrane is an interesting analogy but it lacks a theoretical basis and experimental support. We develop a theoretical model that brings to light the relationship between the conceptual model of a gravity well and an elastic deformation equation of a membrane supporting a heavy ball, and further derive the ‘gravitational constant’ for such a small ‘elastic space’. The experimental data obtained are consistent with the prediction of our model, in mimicking the revolution of a small planet. Teaching practice shows that using an elastic membrane is a simple, intuitive and reliable method to enhance the quality of learning about the effect of gravity.

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

    PubMed

    Wang, Ya-Fang; Yu, Chun-Keung

    2014-04-17

    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.

  9. A generalized chain binomial model with application to HIV infection.

    PubMed

    Ng, J; Orav, E J

    1990-09-01

    The original Reed-Frost formulation of the chain binomial model is mathematically equivalent to a stochastic model allowing a Poisson number of effective contacts in a time interval. Their formulation cannot accommodate survey data that necessarily correspond to more complex distributions of partners or contacts, or to large populations where complete random mixing is unlikely. This paper generalizes the Reed-Frost model to accommodate these situations in both the one- and two-population settings. The extension to multiple populations is also outlined. Using the model to predict HIV incidence in San Francisco's homosexual population, we show that the total number of contacts over all partners is more important than the distribution of contacts among partners in determining the number of infected. PMID:2134482

  10. Global stability of a multiple delayed viral infection model with general incidence rate and an application to HIV infection.

    PubMed

    Ji, Yu

    2015-06-01

    In this paper, the dynamical behavior of a viral infection model with general incidence rate and two time delays is studied. By using the Lyapunov functional and LaSalle invariance principle, the global stabilities of the infection-free equilibrium and the endemic equilibrium are obtained. We obtain a threshold of the global stability for the uninfected equilibrium, which means the disease will be under control eventually. These results can be applied to a variety of viral infections of disease that would make it possible to devise optimal treatment strategies. Numerical simulations with application to HIV infection are given to verify the analytical results.

  11. 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.

  12. Slice Culture Modeling of Central Nervous System (CNS) Viral Infection

    PubMed Central

    Dionne, Kalen R.; Tyler, Kenneth L.

    2016-01-01

    The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease. Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize “CNS-specific” cytokine production, and (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology. PMID:23975824

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Interaction of a peptide derived from C-terminus of human TRPA1 channel with model membranes mimicking the inner leaflet of the plasma membrane.

    PubMed

    Witschas, Katja; Jobin, Marie-Lise; Korkut, Dursun Nizam; Vladan, Maria Magdalena; Salgado, Gilmar; Lecomte, Sophie; Vlachova, Viktorie; Alves, Isabel D

    2015-05-01

    The transient receptor potential ankyrin 1 channel (TRPA1) belongs to the TRP cation channel superfamily that responds to a panoply of stimuli such as changes in temperature, calcium levels, reactive oxygen and nitrogen species and lipid mediators among others. The TRP superfamily has been implicated in diverse pathological states including neurodegenerative disorders, kidney diseases, inflammation, pain and cancer. The intracellular C-terminus is an important regulator of TRP channel activity. Studies with this and other TRP superfamily members have shown that the C-terminus association with lipid bilayer alters channel sensitivity and activation, especially interactions occurring through basic residues. Nevertheless, it is not yet clear how this process takes place and which regions in the C-terminus would be responsible for such membrane recognition. With that in mind, herein the first putative membrane interacting region of the C-terminus of human TRPA1, (corresponding to a 29 residue peptide, IAEVQKHASLKRIAMQVELHTSLEKKLPL) named H1 due to its potential helical character was chosen for studies of membrane interaction. The affinity of H1 to lipid membranes, H1 structural changes occurring upon this interaction as well as effects of this interaction in lipid organization and integrity were investigated using a biophysical approach. Lipid models systems composed of zwitterionic and anionic lipids, namely those present in the lipid membrane inner leaflet, where H1 is prone to interact, where used. The study reveals a strong interaction and affinity of H1 as well as peptide structuration especially with membranes containing anionic lipids. Moreover, the interactions and peptide structure adoption are headgroup specific.

  5. β-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): the first step towards an experimental model for sporadic ALS.

    PubMed

    de Munck, Estefanía; Muñoz-Sáez, Emma; Miguel, Begoña G; Solas, M Teresa; Ojeda, Irene; Martínez, Ana; Gil, Carmen; Arahuetes, Rosa Ma

    2013-09-01

    β-N-methylamino-l-alanine (L-BMAA) is a neurotoxic amino acid that has been related to various neurodegenerative diseases. The aim of this work was to analyze the biotoxicity produced by L-BMAA in vivo in rats, trying to elucidate its physiopathological mechanisms and to search for analogies between the found effects and pathologies like Amyotrophic Lateral Sclerosis (ALS). Our data demonstrated that the neurotoxic effects in vivo were dosage-dependent. For evaluating the state of the animals, a neurological evaluation scale was developed as well as a set of functional tests. Ultrastructural cell analysis of spinal motoneurons has revealed alterations both in endoplasmic reticulum and mitochondria. Since GSK3β could play a role in some neuropathological processes, we analyzed the alterations occurring in GSK3β levels in L-BMAA treated rats, we have observed an increase in the active form of GSK3β levels in lumbar spinal cord and motor cerebral cortex. On the other hand, (TAR)-DNA-binding protein 43 (TDP-43) increased in L-BMAA treated animals. Our results indicated that N-acetylaspartate (NAA) declined in animals treated with L-BMAA, and the ratio of N-acetylaspartate/choline (NAA/Cho), N-acetylaspartate/creatine (NAA/Cr) and N-acetylaspartate/choline+creatine (NAA/Cho+Cr) tended to decrease in lumbar spinal cord and motor cortex. This project offers some encouraging results that could help establishing the progress in the development of an animal model of sporadic ALS and L-BMAA could be a useful tool for this purpose.

  6. 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

  7. 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

  8. 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

  9. 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

  10. Animal models of Middle East Respiratory Syndrome coronavirus infection

    PubMed Central

    van Doremalen, Neeltje; Munster, Vincent J.

    2015-01-01

    The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used laboratory animal species such as Syrian hamsters, mice and ferrets are not susceptible to MERS-CoV, due to differences in the MERS-CoV receptor dipeptyl peptidase 4 (DPP4). The initially developed animal models comprise two nonhuman primate species, the rhesus macaque and the common marmoset. Rhesus macaques develop a mild to moderate respiratory disease upon inoculation, reminiscent of milder MERS cases, whereas marmosets develop a moderate to severe respiratory disease, recapitulating the severe disease observed in some patients. Dromedary camels, considered to be the reservoir for MERS-CoV, develop a mild upper respiratory tract infection with abundant viral shedding. Although normal mice are not susceptible to MERS-CoV, expression of the human DPP4 (hDPP4) overcomes the lack of susceptibility. Transgenic hDPP4 mice develop severe and lethal respiratory disease upon inoculation with MERS-CoV. These hDPP4 transgenic mice are potentially the ideal first line animal model for efficacy testing of therapeutic and prophylactic countermeasures. Further characterization of identified countermeasures would ideally be performed in the common marmoset model, due to the more severe disease outcome. This article forms part of a symposium in Antiviral Research on “From SARS to MERS: research on highly pathogenic human coronaviruses.” PMID:26192750

  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. Rare Mimickers of Exostosis: A Case Series

    PubMed Central

    Perubhotla, Lakshmi Manasa

    2016-01-01

    Exophytic growths from bones are a common entity. Osteochondroma is the most common benign exophytic lesion and we tend to diagnose every benign looking exophytic lesion as osteochondroma. Here we reported two entities of cases, one was Nora’s lesion and another one was supracondylar process of humerus, both of which were mimickers of osteochondroma and their salient and differentiating features from osteochondromas.

  13. Pulmonary hyalinizing granuloma mimicking lung carcinoma.

    PubMed

    Basoglu, A; Findik, S; Celik, B; Yildiz, L

    2006-06-01

    Pulmonary hyalinizing granuloma has rarely been reported and is a benign entity of unknown origin. The chest radiograph reveals multiple and frequently bilateral pulmonary nodules. We describe a patient with pulmonary hyalinizing granuloma who presented with a central mass in the left lung mimicking lung carcinoma. PMID:16755455

  14. [Two cystic retroperitoneal lesions mimicking adrenal cysts].

    PubMed

    Grabellus, F; Dereskewitz, C; Schmitz, K J; Kaiser, G M; Kühl, H; Kersting, C; Frilling, A; Metz, K A; Baba, H A

    2005-05-01

    Adrenal cysts are uncommon lesions and most of them are found incidentally during abdominal imaging. We report on two benign extraadrenal lesions mimicking adrenal tumors in abdominal imaging. The histopathological investigation of the lesions revealed a foregut duplication cyst of the lesser gastric curvature and an epithelial inclusion cyst (epidermoid cyst) in an intrapancreatic accessory spleen respectively.

  15. 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

  16. A nosocomial epidemic model with infection of patients due to contaminated rooms.

    PubMed

    Browne, Cameron; Webb, Glenn F

    2015-08-01

    A model of epidemic bacterial infections in hospitals is developed. The model incorporates the infection of patients and the contamination of healthcare workers due to environmental causes. The model is analyzed with respect to the asymptotic behavior of solutions. The model is interpreted to provide insight for controlling these nosocomial epidemics.

  17. Osteoid osteoma mimicking monoarticular juvenile idiopathic arthritis in a girl.

    PubMed

    Massei, Francesco; Laccetta, Gianluigi; Barrani, Monica; Fabbri, Luca; Zampa, Virna; Paolicchi, Alessandro; Cioni, Roberto; Ciancia, Eugenio Mario; Scaglione, Michelangelo; Consolini, Rita

    2016-08-01

    Osteoid osteoma (OO) is a benign osteogenic neoplasm, usually affecting children and young adults, that is typically characterized by nocturnal pain and response to non-steroidal anti-inflammatory drugs. OO is frequently misdiagnosed because it mimics juvenile idiopathic arthritis (JIA), bone infection or malignancy. Herein we report the case of a girl who presented with chronic monoarthritis of the knee mimicking JIA. After 1 year, OO of the femoral distal metaphysis was diagnosed. OO was treated with computed tomography-guided radiofrequency ablation with disappearance of the symptoms and resolution of the neoplasm. No recurrences have been observed 3 years after the treatment. This case highlights that intra-articular or juxta-articular OO should be suspected in the case of misleading symptoms and signs, such as swelling, lack of typical pain and synovial thickening on ultrasound; needle biopsy of the lesion is necessary in the case of confusing imaging.

  18. Cervical vertebral actinomycosis mimicking malignancy in a paediatric patient.

    PubMed

    Prajapati, Shyam; Yoon, Daniel J; Benitez, Carlos L; Buyuk, Arzu

    2016-01-01

    Actinomyces spp are found in the flora of the oral cavity and vagina and may cause infection with abscess formation and draining sinuses. Cervicofacial manifestations of actinomycosis involve head and neck soft tissue, however, spread to the cervical spine is rare. We report a case of an 8-year-old boy, presenting with neck pain for 1 month and denying a history of trauma or procedures. Radiography revealed an ulceration of the posterior oropharyngeal mucosa with a defect extending to the C1-C2 vertebra, mimicking a neoplastic process. The patient underwent laryngoscopy and multiple biopsies were taken from the ulcer and bone, showing severe osteomyelitis and intraosseous filamentous organisms, morphologically consistent with Actinomyces spp. The boy received long-term antibiotics with response to treatment. Actinomycosis has rarely been reported in the cervical vertebrae of paediatric patients. This should be considered as a differential diagnosis for such a presentation as prompt antibiotic treatment may be lifesaving. PMID:27033296

  19. The role of seasonality and import in a minimalistic multi-strain dengue model capturing differences between primary and secondary infections: complex dynamics and its implications for data analysis.

    PubMed

    Aguiar, Maíra; Ballesteros, Sebastien; Kooi, Bob W; Stollenwerk, Nico

    2011-11-21

    In many countries in Asia and South-America dengue fever (DF) and dengue hemorrhagic fever (DHF) has become a substantial public health concern leading to serious social-economic costs. Mathematical models describing the transmission of dengue viruses have focussed on the so-called antibody-dependent enhancement (ADE) effect and temporary cross-immunity trying to explain the irregular behavior of dengue epidemics by analyzing available data. However, no systematic investigation of the possible dynamical structures has been performed so far. Our study focuses on a seasonally forced (non-autonomous) model with temporary cross-immunity and possible secondary infection, motivated by dengue fever epidemiology. The notion of at least two different strains is needed in a minimalistic model to describe differences between primary infections, often asymptomatic, and secondary infection, associated with the severe form of the disease. We extend the previously studied non-seasonal (autonomous) model by adding seasonal forcing, mimicking the vectorial dynamics, and a low import of infected individuals, which is realistic in the dynamics of dengue fever epidemics. A comparative study between three different scenarios (non-seasonal, low seasonal and high seasonal with a low import of infected individuals) is performed. The extended models show complex dynamics and qualitatively a good agreement between empirical DHF monitoring data and the obtained model simulation. We discuss the role of seasonal forcing and the import of infected individuals in such systems, the biological relevance and its implications for the analysis of the available dengue data. At the moment only such minimalistic models have a chance to be qualitatively understood well and eventually tested against existing data. The simplicity of the model (low number of parameters and state variables) offer a promising perspective on parameter values inference from the DHF case notifications.

  20. Understanding Lipid Recognition by Protein-Mimicking Cyclic Peptides.

    PubMed

    Hosseini, Azade S; Zheng, Hong; Gao, Jianmin

    2014-10-21

    This paper describes our investigation of the structural determinants of a designed cyclic peptide (cLac, cyclic peptide mimicking lactadherin)(1) for phosphatidylserine (PS) recognition. A highly efficient strategy that takes advantage of the native chemical ligation (NCL) chemistry has been developed for the synthesis and labeling of cyclic peptides in general. Ala scanning of the cLac peptide revealed a sophisticated model for PS binding, in which the peptide scaffold assembles multiple polar residues to balance the desolvation and electrostatic interactions (salt bridge and hydrogen bonding) to achieve lipid selectivity. The results suggest that cLac effectively mimics the membrane binding mechanism of the parent protein lactadherin.

  1. Basic Reproduction Number of a Gamma-Distributed Within-Host Infection Model

    NASA Astrophysics Data System (ADS)

    Rodriguez, Irma; Dobrovolny, Hana

    2015-03-01

    In epidemiology, the basic reproduction number (R0) is used to measure the spread potential of a disease. It is defined as the number of secondary infections produced by a first infection in a homogeneous susceptible population. Traditional ordinary differential equation infection models assume exponential transitions between different stages of cell infection. This assumption is not biologically realistic, so non-exponential models are now being investigated. The basic reproduction number of non-exponential models has yet to be calculated. Here we present an analysis of a gamma-distributed model that has allowed us to calculate R0 for this model.

  2. Stochastic disease dynamics of a hospital infection model.

    PubMed

    Wang, Xia; Xiao, Yanni; Wang, Junrui; Lu, Xinxin

    2013-01-01

    A stochastic model for hospital infection incorporating both direct transmission and indirect transmission via free-living bacteria in the environment is investigated. We examine the long term behavior of the model by calculating a stationary distribution and normal approximation of the distribution. The quasi-stationary distribution of the model is studied to investigate the models' behavior before extinction and the time to extinction. Numerical results show agreement between the calculated distributions and results of event-driven simulations. Hand hygiene of volunteers is more effective in terms of reducing the mean (or standard deviation) of the stationary distribution of colonized patients and the expected time to extinction compared to hand hygiene of health care workers (HCWs), on the basis of our parameter values. However, the indirect (or direct) transmission rate can lead to either increase or decrease in the standard deviation of the stationary distribution, but the impact of the indirect transmission is much greater than that of the direct transmission. The findings suggest that isolation of new admitted colonized patients is most effective in reducing both the mean and standard deviation of the stationary distribution and measures related to indirect transmission are secondary in their effects compared to other interventions. PMID:23103300

  3. Mimicking interacting relativistic theories with stationary pulses of light.

    PubMed

    Angelakis, Dimitris G; Huo, Ming-Xia; Chang, Darrick; Kwek, Leong Chuan; Korepin, Vladimir

    2013-03-01

    One of the most well known relativistic field theory models is the Thirring model. Its realization can demonstrate the famous prediction for the renormalization of mass due to interactions. However, experimental verification of the latter requires complex accelerator experiments whereas analytical solutions of the model can be extremely cumbersome to obtain. In this work, following Feynman's original proposal, we propose an alternative quantum system as a simulator of the Thirring model dynamics. Here, the relativistic particles are mimicked, counterintuitively, by polarized photons in a quantum nonlinear medium. We show that the entire set of regimes of the Thirring model--bosonic or fermionic, and massless or massive--can be faithfully reproduced using coherent light trapping techniques. The correlation functions of the model can be extracted by simple probing of the coherence functions of the output light using standard optical techniques.

  4. 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,...

  5. A Stochastic Model for Infective Events in Operating Room Caused by Air Contamination

    NASA Astrophysics Data System (ADS)

    Abundo, Paolo; Rosato, Nicola; Abundo, Mario

    2008-07-01

    We propose a simple stochastic model for the movement of a potentially infective particle in operating room in which the local air contamination level is reduced by using a double laminar flow. Numerical simulation is used to obtain qualitative scenario analysis, in order to prevent infection, i.e. impact of the infective particle with the surgical wound, during the operation.

  6. Immune response to infection by Leishmania: A mathematical model.

    PubMed

    Siewe, Nourridine; Yakubu, Abdul-Aziz; Satoskar, Abhay R; Friedman, Avner

    2016-06-01

    Leishmaniasis is a disease caused by the Leishmania parasites. The injection of the parasites into the host occurs when a sand fly, which is the vector, bites the skin of the host. The parasites, which are obligate, take advantage of the immune system response and invade both the classically activated macrophages (M1) and the alternatively activated macrophages (M2). In this paper, we develop a mathematical model to explain the evolution of the disease. Simulations of the model show that, M2 macrophages steadily increase and M1 macrophages steadily decrease, while M1+M2 reach a steady state which is approximately the same as at healthy state of the host. Furthermore, the ratio of Leishmania parasites to macrophages depends homogeneously on their ratio at the time of the initial infection, in agreement with in vitro experimental data. The model is used to simulate treatment by existing or potential new drugs, and to compare the efficacy of different schedules of drug delivery. PMID:26987853

  7. Use of viral infections in animal models to assess changes in the immune system.

    PubMed Central

    Kern, E R

    1982-01-01

    Viral infections in animal models appear to be ideal systems for determining toxicity to the immune system by environmental substances. Since many viral infections that are utilized in animals produce systemic disease, these models provide an opportunity to evaluate the interaction between virus and components of host resistance. In these infections it is possible to delineate the role of antibody, interferon, cell-mediated immunity, neutrophils and macrophages in response to infection. A change in any of these components responsible for resistance to a particular virus may be correlated with an alteration of mortality an pathogenesis of the viral infection. Three experimental viral infections in mice that are potential candidates for use in determining immunotoxicity are discussed in terms of the response of individual components of resistance to infection and how changes in there components result in alterations of viral pathogenesis. The resistance to encephalomyocarditis virus infection in mice appears to be primarily mediated by antibody and interferon while with herpes simplex virus, infections are mainly controlled through cell-mediated immunity, macrophages, and possible interferon. Cellular immunity also appears to be primarily responsible for resistance to cytomegalovirus infections. Therefore, it is important in the use of these systems for evaluating immunotoxicity to define the pathogenesis of the viral infection and the specific host responses to these infections and to be able to correlate a change in host resistance with an alteration of the viral infection. PMID:6174323

  8. Gnotobiotic Piglet Infection Model for Evaluating the Safe Use of Antibiotics against Escherichia coli O157:H7 Infection

    PubMed Central

    Zhang, Quanshun; Donohue-Rolfe, Arthur; Krautz-Peterson, Greice; Sevo, Milica; Parry, Nicola; Abeijon, Claudia; Tzipori, Saul

    2010-01-01

    Background Shiga toxin (Stx)–producing Escherichia coli (STEC), especially O157:H7, cause bloody diarrhea, and in 3%–15% of individuals the infection leads to hemolytic uremic syndrome (HUS) or other complications. Use of antibiotics to treat STEC infections is controversial. Here, we describe the use of piglets to evaluate the efficacy and mechanism of action of antibiotics in these infections. Methods The effects of 2 antibiotics on STEC toxin production and their mechanisms of action were first determined by enzyme-linked immunosorbent assay and subsequently evaluated clinically in the gnotobiotic piglet infection model. Results In vitro treatment of clinical and isogenic strains with ciprofloxacin increased the production of Stx2 via phage induction but not the production of Stx1. Azithromycin caused no significant increase in toxin production. After treatment with ciprofloxacin, infected piglets had diarrhea and the severe fatal neurological symptoms associated with Stx2 intoxication. Characteristic petechial hemorrhages in the cerebellum were more severe in ciprofloxacin-treated animals than in control animals. In contrast, azithromycin-treated piglets survived the infection and had little or no brain hemorrhaging. Conclusions The increased in vitro toxin production caused by ciprofloxacin was strongly correlated with death and an increased rate of cerebellar hemorrhage, in contrast to the effect of azithromycin. The piglet is a suitable model for determining the effectiveness and safety of antibiotics available to treat patients. PMID:19125676

  9. Characterization of transverse isotropy in compressed tissue-mimicking phantoms.

    PubMed

    Urban, Matthew W; Lopera, Manuela; Aristizabal, Sara; Amador, Carolina; Nenadic, Ivan; Kinnick, Randall R; Weston, Alexander D; Qiang, Bo; Zhang, Xiaoming; Greenleaf, James F

    2015-06-01

    Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue-mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest that makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested six phantoms made with different concentrations of gelatin and agar. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique. Autocorrelation was applied to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0° to 360°, where the stress is applied along 0° to 180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue-mimicking phantom. PMID:26067038

  10. Characterization of transverse isotropy in compressed tissue-mimicking phantoms.

    PubMed

    Urban, Matthew W; Lopera, Manuela; Aristizabal, Sara; Amador, Carolina; Nenadic, Ivan; Kinnick, Randall R; Weston, Alexander D; Qiang, Bo; Zhang, Xiaoming; Greenleaf, James F

    2015-06-01

    Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue-mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest that makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested six phantoms made with different concentrations of gelatin and agar. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique. Autocorrelation was applied to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0° to 360°, where the stress is applied along 0° to 180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue-mimicking phantom.

  11. Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.

    PubMed

    Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher

    2015-08-01

    Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

  12. Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

    PubMed Central

    Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F.; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon

    2015-01-01

    Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. PMID:26092919

  13. Cardiac sarcoidosis mimicking right ventricular dysplasia.

    PubMed

    Shiraishi, Jun; Tatsumi, Tetsuya; Shimoo, Kazutoshi; Katsume, Asako; Mani, Hiroki; Kobara, Miyuki; Shirayama, Takeshi; Azuma, Akihiro; Nakagawa, Masao

    2003-02-01

    A 59-year-old woman with skin sarcoidosis was admitted to hospital for assessment of complete atrioventricular block. Cross-sectional echocardiography showed that the apical free wall of the right ventricle was thin and dyskinetic with dilation of the right ventricle. Thallium-201 myocardial imaging revealed a normal distribution. Both gallium-67 and technetium-99m pyrophosphate scintigraphy revealed no abnormal uptake in the myocardium. Right ventriculography showed chamber dilation and dyskinesis of the apical free wall, whereas left ventriculography showed normokinesis, mimicking right ventricular dysplasia. Cardiac sarcoidosis was diagnosed on examination of an endomyocardial biopsy specimen from the right ventricle. A permanent pacemaker was implanted to manage the complete atrioventricular block. After steroid treatment, electrocardiography showed first-degree atrioventricular block and echocardiography revealed an improvement in the right ventricular chamber dilation. Reports of cardiac sarcoidosis mimicking right ventricular dysplasia are extremely rare and as this case shows, right ventricular involvement may be one of its manifestations.

  14. Mad honey intoxication mimicking acute coronary syndrome.

    PubMed

    Dur, Ali; Sonmez, Ertan; Civelek, Cemil; AhmetTurkdogan, Kenan; AkifVatankulu, Mehmet; Sogut, Ozgur

    2014-09-01

    Mad honey intoxication or grayanotoxin poisoning is caused by consumption of grayanotoxin-containing toxic honey produced from leaves and flowers of the Rhododendron family. Despite the rarity of intoxication cases, the correct diagnosis and treatment are required because of the significance of haemodynamic disturbance and confounding of symptoms for disease identification. We report herein a case of a patient with mad honey intoxication mimicking acute non-ST segment elevation myocardial infarction and review the pathophysiology and diagnostic considerations.

  15. Diffuse anaplastic leptomeningeal oligodendrogliomatosis mimicking neurosarcoidosis.

    PubMed

    Leep Hunderfund, Andrea N; Zabad, Rana K; Aksamit, Allen J; Morris, Jonathan M; Meyer, Fredric B; Thorell, William E; Parisi, Joseph E; Giannini, Caterina

    2013-06-01

    Diffuse leptomeningeal oligodendrogliomatosis is a rare, frequently fatal CNS malignancy that most often affects children.(1) Although potentially treatable with chemotherapy and radiation, the radiologic findings are nonspecific and pathologic confirmation of the diagnosis is difficult. We describe an adult patient whose initial presentation mimicked neurosarcoidosis. Despite extensive imaging abnormalities, 3 biopsies were required before the diagnosis of diffuse leptomeningeal oligodendrogliomatosis was confirmed. PMID:23914328

  16. [Pulmonary hyalinizing granuloma mimicking pulmonary carcinoma].

    PubMed

    Uçvet, Ahmet; Tözüm, Halil; Gürsoy, Soner; Gülle, Ali Alper; Yaldiz, Sadik; Aydoğdu Dinç, Zekiye

    2006-01-01

    Pulmonary hyalinizing granuloma is a rare fibrosing nodular disease of the lung characterized by solitary or multiple pulmonary nodules. They can occur after inflammatory or post-inflammatory changes. A 60 years old asymptomatic patient admitted to our clinic because of a solid mass of 6 cm in his routine chest radiography. A lobectomy was performed and the histological diagnosis was reported as pulmonary hyalinizing granuloma. This case, mimicking pulmonary carcinoma, is rarely found in the literature. PMID:16615022

  17. Rare Mimickers of Exostosis: A Case Series

    PubMed Central

    Perubhotla, Lakshmi Manasa

    2016-01-01

    Exophytic growths from bones are a common entity. Osteochondroma is the most common benign exophytic lesion and we tend to diagnose every benign looking exophytic lesion as osteochondroma. Here we reported two entities of cases, one was Nora’s lesion and another one was supracondylar process of humerus, both of which were mimickers of osteochondroma and their salient and differentiating features from osteochondromas. PMID:27630926

  18. Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections

    PubMed Central

    Vela, Eric

    2012-01-01

    Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection. PMID:23170184

  19. Establishing a new animal model for hepadnaviral infection: susceptibility of Chinese Marmota-species to woodchuck hepatitis virus infection.

    PubMed

    Wang, Bao-Ju; Tian, Yong-Jun; Meng, Zhong-Ji; Jiang, Min; Wei, Bo-Qing; Tao, Yuan-Qing; Fan, Wei; Li, An-Yi; Bao, Jun-Jie; Li, Xin-Yu; Zhang, Zheng-Mao; Wang, Zhong-Dong; Wang, Hu; Roggendorf, Michael; Lu, Meng-Ji; Yang, Dong-Liang

    2011-03-01

    Hepatitis B virus infection (HBV) is a major medical problem in China. The lack of a suitable infection model in China is recognized as an obstacle for research on HBV in China. Chinese Marmota-species is phylogenetically closely related to Marmota monax, thus, it might be suitable to serve as an animal model for HBV infection. Therefore, we attempted to prove the claim about the existence of woodchuck hepatitis virus (WHV)-like viruses in Chinese Marmota-species and to determine the susceptibility of these species to experimental WHV infection. In the present study, 653 sera from three Chinese Marmota-species, Marmota himalayana, Marmota baibacina and Marmota bobak, were screened for WHV-like viruses by serological and molecular assays. The susceptibility to WHV of three species was investigated by experimental infection and monitored by testing of anti-WHc and WHsAg by ELISA, detection of WHV DNA by PCR, and detection of WHV replication intermediates and antigens in liver samples. No evidence for the existence of a genetically closely related virus to WHV in three Chinese Marmota-species was found by serological assays and PCR. M. himalayana was susceptible to WHV infection as inoculated animals became positive for anti-WHc, WHsAg and WHV DNA. Further, WHV replication intermediates and proteins were detected in liver samples. In contrast, M. baibacina remained negative for tested virological parameters. M. bobak species showed a limited susceptibility to WHV. Our data do not support early reports about WHV-like viruses in China. M. himalayana is suitable for the establishment of a model for hepadnaviral infection.

  20. Bioengineering a humanized acne microenvironment model: Proteomics analysis of host responses to Propionibacterium acnes infection in vivo

    PubMed Central

    Nakatsuji, Teruaki; Shi, Yang; Zhu, Wenhong; Huang, Cheng-Po; Chen, Yun-Ru; Lee, Dong-Youn; Smith, Jeffery W.; Zouboulis, Christos C.; Gallo, Richard L.; Huang, Chun-Ming

    2009-01-01

    Acne is a human disease of the sebaceous hair follicle. Unlike humans, most animals produce little or no triglycerides in hair follicles to harbor Propionibacterium acnes a fact that has encumbered the development of novel treatments for acne lesions. Although genetic mutant mice with acne-like skins have been used for screening anti-acne drugs, the mice generally have deficits in immune system that turns out to be inappropriate to generate antibodies for developing acne vaccines. Here, we employed a bioengineering approach using a tissue chamber integrated with a dermis-based cell-trapped system (DBCTS) to mimic the in vivo microenvironment of acne lesions. Human sebocyte cell lines were grown in DBCTS as a scaffold and inserted into a perforated tissue chamber. After implantation of a tissue chamber bearing human sebocytes into ICR mice, P. acnes or PBS was injected into a tissue chamber to induce host immune response. Infiltrated cells such as neutrophils and macrophages were detectable in tissue chamber fluids. In addition, a proinflammatory cytokine macrophage-inflammatory protein-2 (MIP-2) was elevated after P. acnes injection. In tissue chamber fluids, 13 proteins including secreted proteins and cell matrix derived from mouse, human cells or P. acnes were identified by proteomics using isotope-coded protein label (ICPL) coupled to nano-LC-MS analysis. After P. acnes infection, four proteins including fibrinogen, α polypeptide, fibrinogen β chain, S100A9, and serine protease inhibitor A3K showed altered concentrations in the mimicked acne microenvironment. The bioengineered acne model thus provides an in vivo microenvironment to study the interaction of host with P. acnes and offers a unique set-up for screening novel anti-acne drugs and vaccines. PMID:18651708

  1. Identification of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

    NASA Astrophysics Data System (ADS)

    Kong, Cin; Rahman, Noorsaadah Abd; Nathan, Sheila

    2014-09-01

    The alarming increase of antibiotic-resistant Staphylococcus aureus and a delay in antibiotics development point to the need for novel therapeutic approaches to combat infection. To discover novel anti-infective agents, we screened a number of synthetic compounds comprising mainly of chalcone derivatives to explore their potential in promoting the survival of the nematode Caenorhabditis elegans upon infection by S. aureus. Screening of seven chalcone derivatives using both agar- and liquid-based assays revealed three positive hits that significantly prolonged the survival of S. aureus-infected nematodes. All the hits did not interfere with bacterial growth in vitro, proposing that the three compounds identified most probably act through mechanisms distinct from conventional antibiotics that target bacterial replication.

  2. Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik

    2005-12-01

    This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

  3. Current Animal Models of Postoperative Spine Infection and Potential Future Advances

    PubMed Central

    Stavrakis, A. I.; Loftin, A. H.; Lord, E. L.; Hu, Y.; Manegold, J. E.; Dworsky, E. M.; Scaduto, A. A.; Bernthal, N. M.

    2015-01-01

    Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition, there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions. PMID:26131448

  4. Trickle or clumped infection process? A stochastic model for the infection process of the parasitic roundworm of humans, Ascaris lumbricoides.

    PubMed

    Walker, Martin; Hall, Andrew; Basáñez, María-Gloria

    2010-10-01

    The importance of the mode of acquisition of infectious stages of directly-transmitted parasitic helminths has been acknowledged in population dynamics models; hosts may acquire eggs/larvae singly in a "trickle" type manner or in "clumps". Such models have shown that the mode of acquisition influences the distribution and dynamics of parasite loads, the stability of host-parasite systems and the rate of emergence of anthelmintic resistance, yet very few field studies have allowed these questions to be explored with empirical data. We have analysed individual worm weight data for the parasitic roundworm of humans, Ascaris lumbricoides, collected from a three-round chemo-expulsion study in Dhaka, Bangladesh, with the aim of discerning whether a trickle or a clumped infection process predominates. We found that hosts tend to harbour female worms of a similar weight, indicative of a clumped infection process, but acknowledged that unmeasured host heterogeneities (random effects) could not be completely excluded as a cause. Here, we complement our previous statistical analyses using a stochastic infection model to simulate sizes of individual A. lumbricoides infecting a population of humans. We use the intraclass correlation coefficient (ICC) as a quantitative measure of similarity among simulated worm sizes and explore the behaviour of this statistic under assumptions corresponding to trickle or clumped infections and unmeasured host heterogeneities. We confirm that both mechanisms are capable of generating aggregates of similar-sized worms, but that the particular pattern of ICCs described pre- and post-anthelmintic treatment in the data is more consistent with aggregation generated by clumped infections than by host heterogeneities alone. This provides support to the notion that worms may be acquired in clumps. We discuss our results in terms of the population biology of A. lumbricoides and highlight the significance of our modelling approach for the study of the

  5. Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

    PubMed

    Sulaiman, Helmi; Ismail, Muhammad Dzafir; Jalalonmuhali, Maisarah; Atiya, Nadia; Ponnampalavanar, Sasheela

    2014-08-30

    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

  6. Giant kidney worm (Dioctophyma renale) infection mimicking retroperitoneal neoplasm.

    PubMed

    Sun, T; Turnbull, A; Lieberman, P H; Sternberg, S S

    1986-07-01

    A 50-year-old Chinese man was found by ultrasound and computed tomography to have a retroperitoneal mass in the right upper quadrant of the abdomen. At operation, a hemorrhagic cyst was detected at the upper pole of the right kidney adjacent to the adrenal gland. Microscopic examination revealed that the cyst wall was composed of granulomatous tissue loaded with eggs and cross-sections of parasites, identified as Dioctophyma renale. The eggs were characterized by a birefringent striated double wall. The presence of cross sections of adult worms of D. renale in human tissue has not been previously described. Another unique feature of this case was that the right kidney was intact, as examined grossly at laparotomy and by intravenous pyelography. Eggs were not detected in the urine.

  7. An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation.

    PubMed

    Reis, Sônia Regina Nogueira Ignácio; Sampaio, André Luiz Franco; Henriques, Maria das Graças Muller; Gandini, Mariana; Azeredo, Elzinandes Leal; Kubelka, Claire Fernandes

    2007-12-01

    An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune etiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applied for dengue fever.

  8. A Trichophyton Rubrum Infection Model Based on the Reconstructed Human Epidermis - Episkin®

    PubMed Central

    Liang, Pan-Pan; Huang, Xin-Zhu; Yi, Jin-Ling; Chen, Zhi-Rui; Ma, Han; Ye, Cong-Xiu; Chen, Xian-Yan; Lai, Wei; Chen, Jian

    2016-01-01

    Background: Trichophyton rubrum represents the most common infectious fungus responsible for dermatophytosis in human, but the mechanism involved is still not completely understood. An appropriate model constructed to simulate host infection is the prerequisite to study the pathogenesis of dermatophytosis caused by T. rubrum. In this study, we intended to develop a new T. rubrum infection model in vitro, using the three-dimensional reconstructed epidermis - EpiSkin®, and to pave the way for further investigation of the mechanisms involved in T. rubrum infection. Methods: The reconstructed human epidermis (RHE) was infected by inoculating low-dose (400 conidia) and high-dose (4000 conidia) T. rubrum conidia to optimize the infection dose. During the various periods after infection, the samples were processed for pathological examination and scanning electron microscopy (SEM) observation. Results: The histological analysis of RHE revealed a fully differentiated epidermis with a functional stratum corneum, which was analogous to the normal human epidermis. The results of hematoxylin and eosin staining and the periodic acid-Schiff staining showed that the infection dose of 400 conidia was in accord with the pathological characteristics of host dermatophytosis caused by T. rubrum. SEM observations further exhibited the process of T. rubrum infection in an intuitionistic way. Conclusions: We established the T. rubrum infection model on RHE in vitro successfully. It is a promising model for further investigation of the mechanisms involved in T. rubrum infection. PMID:26712433

  9. The use of animal infection models to study the pathogenesis of melioidosis and glanders.

    PubMed

    Woods, Donald E

    2002-11-01

    The use of animal infection models is central to the study of microbial pathogenesis. In combination with genetic, immunological and antigen purification techniques, much can be learned regarding the pathogenesis of diseases caused by microorganisms. This update focuses on the recent use of animal infection models to study the pathogenesis of melioidosis and glanders.

  10. Modeling Dental Health Care Workers' Risk of Occupational Infection from Bloodborne Pathogens.

    ERIC Educational Resources Information Center

    Capilouto, Eli; And Others

    1990-01-01

    The brief paper offers a model which permits quantification of the dental health care workers' risk of occupationally acquiring infection from bloodborne pathogens such as human immunodeficiency virus and hepatitis B virus. The model incorporates five parameters such as the probability that any individual patient is infected and number of patients…

  11. Optimization of replica exchange molecular dynamics by fast mimicking.

    PubMed

    Hritz, Jozef; Oostenbrink, Chris

    2007-11-28

    We present an approach to mimic replica exchange molecular dynamics simulations (REMD) on a microsecond time scale within a few minutes rather than the years, which would be required for real REMD. The speed of mimicked REMD makes it a useful tool for "testing" the efficiency of different settings for REMD and then to select those settings, that give the highest efficiency. We present an optimization approach with the example of Hamiltonian REMD using soft-core interactions on two model systems, GTP and 8-Br-GTP. The optimization process using REMD mimicking is very fast. Optimization of Hamiltonian-REMD settings of GTP in explicit water took us less than one week. In our study we focus not only on finding the optimal distances between neighboring replicas, but also on finding the proper placement of the highest level of softness. In addition we suggest different REMD simulation settings at this softness level. We allow several replicas to be simulated at the same Hamiltonian simultaneously and reduce the frequency of switching attempts between them. This approach allows for more efficient conversions from one stable conformation to the other.

  12. Non-human primate models of SIV infection and CNS neuropathology.

    PubMed

    Williams, Kenneth; Lackner, Andrew; Mallard, Jaclyn

    2016-08-01

    Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages. Consistent in all of these models are data underscoring the importance of monocyte and macrophage activation, infection and accumulation in the CNS. PMID:27544476

  13. Plasmid CDS5 influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection.

    PubMed

    Ramsey, K H; Schripsema, J H; Smith, B J; Wang, Y; Jham, B C; O'Hagan, K P; Thomson, N R; Murthy, A K; Skilton, R J; Chu, P; Clarke, I N

    2014-08-01

    The native plasmid of both Chlamydia muridarum and Chlamydia trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene. PMID:24866804

  14. Plasmid CDS5 Influences Infectivity and Virulence in a Mouse Model of Chlamydia trachomatis Urogenital Infection

    PubMed Central

    Schripsema, J. H.; Smith, B. J.; Wang, Y.; Jham, B. C.; O'Hagan, K. P.; Thomson, N. R.; Murthy, A. K.; Skilton, R. J.; Chu, P.; Clarke, I. N.

    2014-01-01

    The native plasmid of both Chlamydia muridarum and Chlamydia trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene. PMID:24866804

  15. Modelling and analysis of dynamics of viral infection of cells and of interferon resistance

    NASA Astrophysics Data System (ADS)

    Getto, Ph.; Kimmel, M.; Marciniak-Czochra, A.

    2008-08-01

    Interferons are active biomolecules, which help fight viral infections by spreading from infected to uninfected cells and activate effector molecules, which confer resistance from the virus on cells. We propose a new model of dynamics of viral infection, including endocytosis, cell death, production of interferon and development of resistance. The novel element is a specific biologically justified mechanism of interferon action, which results in dynamics different from other infection models. The model reflects conditions prevailing in liquid cultures (ideal mixing), and the absence of cells or virus influx from outside. The basic model is a nonlinear system of five ordinary differential equations. For this variant, it is possible to characterise global behaviour, using a conservation law. Analytic results are supplemented by computational studies. The second variant of the model includes age-of-infection structure of infected cells, which is described by a transport-type partial differential equation for infected cells. The conclusions are: (i) If virus mortality is included, the virus becomes eventually extinct and subpopulations of uninfected and resistant cells are established. (ii) If virus mortality is not included, the dynamics may lead to extinction of uninfected cells. (iii) Switching off the interferon defense results in a decrease of the sum total of uninfected and resistant cells. (iv) Infection-age structure of infected cells may result in stabilisation or destabilisation of the system, depending on detailed assumptions. Our work seems to constitute the first comprehensive mathematical analysis of the cell-virus-interferon system based on biologically plausible hypotheses.

  16. Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction.

    PubMed

    Chen, S C; You, S H; Liu, C Y; Chio, C P; Liao, C M

    2012-09-01

    The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

  17. A Comprehensive Subcellular Proteomic Survey of Salmonella Grown under Phagosome-Mimicking versus Standard Laboratory Conditions

    SciTech Connect

    Brown, Roslyn N.; Sanford, James A.; Park, Jea H.; Deatherage, Brooke L.; Champion, Boyd L.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2012-06-01

    Towards developing a systems-level pathobiological understanding of Salmonella enterica, we performed a subcellular proteomic analysis of this pathogen grown under standard laboratory and infection-mimicking conditions in vitro. Analysis of proteins from cytoplasmic, inner membrane, periplasmic, and outer membrane fractions yielded coverage of over 30% of the theoretical proteome. Confident subcellular location could be assigned to over 1000 proteins, with good agreement between experimentally observed location and predicted/known protein properties. Comparison of protein location under the different environmental conditions provided insight into dynamic protein localization and possible moonlighting (multiple function) activities. Notable examples of dynamic localization were the response regulators of two-component regulatory systems (e.g., ArcB, PhoQ). The DNA-binding protein Dps that is generally regarded as cytoplasmic was significantly enriched in the outer membrane for all growth conditions examined, suggestive of moonlighting activities. These observations imply the existence of unknown transport mechanisms and novel functions for a subset of Salmonella proteins. Overall, this work provides a catalog of experimentally verified subcellular protein location for Salmonella and a framework for further investigations using computational modeling.

  18. A Mathematical Model of T1D Acceleration and Delay by Viral Infection.

    PubMed

    Moore, James R; Adler, Fred

    2016-03-01

    Type 1 diabetes (T1D) is often triggered by a viral infection, but the T1D prevalence is rising among populations that have a lower exposure to viral infection. In an animal model of T1D, the NOD mouse, viral infection at different ages may either accelerate or delay disease depending on the age of infection and the type of virus. Viral infection may affect the progression of T1D via multiple mechanisms: triggering inflammation, bystander activation of self-reactive T-cells, inducing a competitive immune response, or inducing a regulatory immune response. In this paper, we create mathematical models of the interaction of viral infection with T1D progression, incorporating each of these four mechanisms. Our goal is to understand how each viral mechanism interacts with the age of infection. The model predicts that each viral mechanism has a unique pattern of interaction with disease progression. Viral inflammation always accelerates disease, but the effect decreases with age of infection. Bystander activation has little effect at younger ages and actually decreases incidence at later ages while accelerating disease in mice that do get the disease. A competitive immune response to infection can decrease incidence at young ages and increase it at older ages, with the effect decreasing over time. Finally, an induced Treg response decreases incidence at any age of infection, but the effect decreases with age. Some of these patterns resemble those seen experimentally. PMID:27030351

  19. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model)

    PubMed Central

    Broeckel, Rebecca; Haese, Nicole; Messaoudi, Ilhem; Streblow, Daniel N.

    2015-01-01

    Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. PMID:26389957

  20. A Bayesian Weibull survival model for time to infection data measured with delay.

    PubMed

    Kostoulas, Polychronis; Nielsen, Søren S; Browne, William J; Leontides, Leonidas

    2010-05-01

    Survival analysis methods can be used to identify factors associated with the time to induction of infection. In the absence of a perfect test, detection of infection is generally delayed and depends on the duration of the latent infection period. We assess, via simulations, the impact of ignoring the delayed detection of infection on estimated survival times and propose a Bayesian Weibull regression model, which adjusts for the delayed detection of infection. The presence of non-differential detection delay seriously biased the baseline hazard and the shape of the hazard function. For differential detection delay, the associated regression coefficients were also biased. The extent of bias largely depended on the longevity of the delay. In all considered simulation scenarios our model led to corrected estimates. We utilized the proposed model in order to assess the age at natural infection with Mycobacterium avium subsp. paratuberculosis (MAP) in Danish dairy cattle from the analysis of available time to milk-seropositivity data that detected infection with delay. The proposed model captured the inverse relationship between the incidence rate of infection and that of seroconversion with time: susceptibility to infection decreases with time (shape parameter under the proposed model was rho=0.56<1), while older animals had a higher probability of sero-converting (rho=2.67>1, under standard Weibull regression). Cows infected earlier in their lives were more likely to subsequently shed detectable levels of MAP and, hence, be a liability to herd-mates. Our approach can be particularly useful in the case of chronic infections with a long latent infection period, which, if ignored, severely affects survival estimates.

  1. Modeling the effects of prior infection on vaccine efficacy

    SciTech Connect

    Smith, D.J.; Forrest, S.; Ackley, D.H.; Perelson, A.S.

    1997-11-01

    We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.

  2. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer

    PubMed Central

    Hong, Su Jin; Kim, Tae Jung; Lee, Jae-Ho; Park, Jeong-Soo

    2016-01-01

    Abstract To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass-like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed. Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6–7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens. NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID:27367996

  3. Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis

    PubMed Central

    Kalmar, Isabelle; Vanrompay, Daisy

    2013-01-01

    Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. PMID:23836817

  4. Theoretical models for near forward light scattering by a Plasmodium falciparum infected red blood cell

    NASA Astrophysics Data System (ADS)

    Sharma, S. K.

    2012-12-01

    A number of experimental elastic light scattering studies have been performed in the past few years with the aim of developing automated in vivo tools for differentiating a healthy red blood cell from a Plasmodium falciparum infected cell. This paper examines some theoretical aspects of the problem. An attempt has been made to simulate the scattering patterns of healthy as well as infected individual red blood cells. Two models, namely, a homogeneous sphere model and a coated sphere model have been considered. The scattering patterns predicted by these models are examined. A possible method for discriminating infected red blood cells from healthy ones has been suggested.

  5. A murine model of coxsackievirus A16 infection for anti-viral evaluation.

    PubMed

    Liu, Qingwei; Shi, Jinping; Huang, Xulin; Liu, Fei; Cai, Yicun; Lan, Ke; Huang, Zhong

    2014-05-01

    Coxsackievirus A16 (CA16) is one of the main causative agents of hand, foot and mouth disease (HFMD), which is a common infectious disease in children. CA16 infection may lead to severe nervous system damage and even death in humans. However, study of the pathogenesis of CA16 infection and development of vaccines and anti-viral agents are hindered partly by the lack of an appropriate small animal model. In the present study, we developed and characterized a murine model of CA16 infection. We show that neonatal mice are susceptible to CA16 infection via intraperitoneal inoculation. One-day-old mice infected with 2×10(6)TCID50 of CA16/SZ05 strain consistently exhibited clinical signs, including reduced mobility, and limb weakness and paralysis. About 57% of the mice died within 14days after infection. Significant damage in the brainstem, limb muscles and intestines of the infected mice in the moribund state was observed by histological examination, and the presence of CA16 in neurons of the brainstem was demonstrated by immunohistochemical staining with a CA16-specific polyclonal antibody, strongly suggesting the involvement of the central nervous system in CA16 infection. Analysis of virus titers in various organs/tissues collected at 3, 6 and 9days post-infection, showed that skeletal muscle was the major site of virus replication at the early stage of infection, while the virus mainly accumulated in the brain at the late stage. In addition, susceptibility of mice to CA16 infection was found to be age dependent. Moreover, different CA16 strains could exhibit varied virulence in vivo. Importantly, we demonstrated that post-exposure treatment with an anti-CA16 monoclonal antibody fully protected mice against lethal CA16 infection. Collectively, these results indicate the successful development of a CA16 infection mouse model for anti-viral evaluation. PMID:24583030

  6. Novel models for bacterial colonization and infection of full-thickness wounds in rats.

    PubMed

    Asada, Mayumi; Nakagami, Gojiro; Minematsu, Takeo; Nagase, Takashi; Akase, Tomoko; Huang, Lijuan; Yoshimura, Kotaro; Sanada, Hiromi

    2012-01-01

    An animal model is needed to study the pathophysiology of wound infections; however, an animal model that is reproducible and clinically relevant has not previously been available. In addition, an animal model of wound colonization generated in a manner similar to the wound infection model would be useful. Here, we describe new animal models of the wound infection continuum for the characterization of essential host-pathogen relationships. We determined the conditions needed to establish rat models of stable wound colonization and infection, without the use of disturbing factors (e.g., foreign bodies or induction of diabetes mellitus). We found that the age of the rats, bacterial inoculum size, and wound location were important elements in generating reproducible, obvious, spreading wound infections. We inoculated approximately 6-month-old rats with 2.06 × 10(9) or 4.12 × 10(9) colony-forming units of Pseudomonas aeruginosa to generate the wound colonization and wound infection models, respectively. Wounds were made 2 cm cranial to the greater trochanter. These clinically relevant and highly reproducible animal models can be used to investigate the mechanisms of wound infection and monitor the effect of therapeutic agents in vivo.

  7. Chondroblastoma of the acromion mimicking fibrous dysplasia.

    PubMed

    Gebert, Carsten; Hardes, Jendrik; Streitbürger, Arne; Vieth, Volker; Bürger, Horst; Winkelmann, Winfried; Gosheger, Georg

    2004-12-01

    The authors report the case of a 65-year-old man who presented with an expansive osteolytic lesion in the right acromion, mimicking cystic fibrous dysplasia. Magnetic resonance imaging showed a lesion with intermediate-signal intensity on T1-weighted images and a high-signal intensity on fat suppressed T2-weighted images. The biopsy led to the diagnosis of chondroblastoma. This tumour is rare in flat bones, and may mimic other benign or malignant lesions. It is therefore essential to perform a biopsy in order to obtain a definite diagnosis. The acromion was excised, and replaced with an iliac crest graft. PMID:15669467

  8. Primary cardiac lymphoma mimicking infiltrative cardiomyopathy.

    PubMed

    Lee, Ga Yeon; Kim, Won Seog; Ko, Young-Hyeh; Choi, Jin-Oh; Jeon, Eun-Seok

    2013-05-01

    Primary cardiac lymphoma is a rare malignancy which has been described as thickened myocardium due to the infiltration of atypical lymphocytes and accompanying intracardiac masses. Here, we report a case of a primary cardiac lymphoma without demonstrable intracardiac masses, mimicking infiltrative cardiomyopathy. A 40-year-old male presented with exertional dyspnoea and was diagnosed as having restrictive cardiomyopathy with severely decreased LV systolic function. Endomyocardial biopsy was performed and the diagnosis of primary cardiac lymphoma was confirmed. After appropriate chemotherapy, he recovered his systolic function fully. PMID:23248217

  9. Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

    PubMed

    Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

    2008-01-01

    Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

  10. Neglected foreign body aspiration mimicking bronchial carcinoma.

    PubMed

    Afghani, Reza; Khandashpour Ghomi, Mahmoud; Khandoozi, Seyed Reza; Yari, Behrouz

    2016-07-01

    Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma. PMID:27273232

  11. Effect of Vitamin A on Listeria monocytogenes Infection in a Silkworm Model

    PubMed Central

    Watanabe, Kenta; Shimizu, Takashi; Watarai, Masahisa

    2016-01-01

    Insect infection models have been used increasingly to study various pathogenic agents in evaluations of pathogenicity and drug efficacy. In this study, we demonstrated that larvae of the silkworm Bombyx mori are useful for studying Listeria monocytogenes infections in insects. Infection with the L. monocytogenes wild-type strain induced silkworm death. Infection by a listeriolysin O (LLO) deletion mutant also induced silkworm death, but the bacterial numbers in silkworms were lower than those of the wild-type strain. Intracellular growth was observed when the silkworm ovary-derived cell line BmN4 was infected with the wild-type strain. Explosive replication was not observed in BmN4 cells infected with the LLO mutant and the bacterial numbers of the LLO mutant were lower than those of the wild-type strain. Pretreatment with vitamin A did not affect silkworm mortality after bacterial infection, but the efficiency of infecting the hemocytes and BmN4 cells was decreased with vitamin A treatment. Our results indicate that silkworm larvae are a useful insect infection model for L. monocytogenes and that vitamin A has protective effects against bacterial infection in silkworms. PMID:27669511

  12. Zebrafish as a new model for herpes simplex virus type 1 infection.

    PubMed

    Burgos, Javier S; Ripoll-Gomez, Jorge; Alfaro, Juan M; Sastre, Isabel; Valdivieso, Fernando

    2008-12-01

    The zebrafish (Danio rerio) is rapidly gaining ground as a disease model. However, until now, the use of this species with human pathogens has been restricted to just three bacteria; no studies involving viruses that infect humans are recorded. In this study, the zebrafish was used as a model of herpes simplex virus type 1 (HSV-1) infection of the nervous system. Fish infected using viral culture supernatants showed detectable HSV-1 DNA concentrations 1-4 days after inoculation, indicating that this virus can experimentally infect and persist in this host. The kinetics of infection was dose dependent, especially in the head. Histological immunodetection of HSV-1 glycoproteins confirmed the presence of HSV-1 in the organs studied; infection led to histopathological changes. Moreover, the suppression of the immune system by cyclophosphamide and the antiviral effect of acyclovir were demonstrated. The infection of the encephalon was studied in detail, and the time course of viral colonization recorded. Immunofluorescence studies provided immunoreactive evidence of viral antigens in the encephalon and spinal cord. Viruses cleared from infected brains showed the ability to infect human neuroblastoma cells. This study is the first to demonstrate HSV-1 infection in the zebrafish and manifests the potential use of this species in herpesvirus studies.

  13. Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection

    PubMed Central

    Bailey, Adam L.; Lauck, Michael; Mohns, Mariel; Peterson, Eric J.; Beheler, Kerry; Brunner, Kevin G.; Crosno, Kristin; Mejia, Andres; Mutschler, James; Gehrke, Matthew; Greene, Justin; Ericsen, Adam J.; Weiler, Andrea; Lehrer-Brey, Gabrielle; Friedrich, Thomas C.; Sibley, Samuel D.; Kallas, Esper G.; Capuano, Saverio; Rogers, Jeffrey; Goldberg, Tony L.; Simmons, Heather A.; O’Connor, David H.

    2015-01-01

    Human Pegivirus (HPgV) – formerly known as GB virus C and hepatitis G virus – is a poorly characterized RNA virus that infects approximately one-sixth of the global human population and is transmitted frequently in the blood supply. Here, we create an animal model of HPgV infection by infecting macaque monkeys with a new simian pegivirus (SPgV) discovered in wild baboons. Using this model, we provide a high-resolution, longitudinal picture of SPgV viremia where the dose, route, and timing of infection are known. We detail the highly-variable acute-phase of SPgV infection, showing that the viral load trajectory early in infection is dependent upon the infecting dose, whereas the chronic-phase viremic set-point is not. We also show that SPgV has an extremely low propensity for accumulating sequence variation, with no consensus-level variants detected during the acute phase of infection and an average of only 1.5 variants generated per 100 infection days. Finally, we show that SPgV RNA is highly concentrated in only two tissues: spleen and bone marrow, with bone marrow likely producing the majority of virus detected in plasma. Together, these results reconcile several paradoxical observations from cross-sectional analyses of HPgV in humans and provide an animal model for studying pegivirus biology. PMID:26378244

  14. An in vitro model of bacterial infections in wounds and other soft tissues.

    PubMed

    Werthén, Maria; Henriksson, Lina; Jensen, Peter Østrup; Sternberg, Claus; Givskov, Michael; Bjarnsholt, Thomas

    2010-02-01

    There is growing evidence that bacteria play a crucial role in the persistence of chronic wounds. These bacteria are most probably present in polymer-embedded aggregates that represent the biofilm mode of growth. Much work has been carried out to study the development of biofilms in vitro, in particular in attachment to solid surfaces. The observations from the chronic wounds indicate that the bacteria are not attached to a solid surface. Consequently, a new in vitro model is required to investigate biofilms in more wound-like settings. This study describes such a novel in vitro model, with bacteria growing as biofilm aggregates in a collagen gel matrix with serum protein mimicking the wound bed of chronic wounds. The model was verified to comprise important hallmarks of biofilms such as the bacterial embedment in a matrix and increased antibiotic tolerance. Furthermore, we have verified the relevance of the model by comparing the organization of the bacteria in the model with the organization of the bacteria in a real chronic wound. We believe that we have developed an important new model for investigating bacterial biofilms in chronic wounds. This model may be used to study biofilm development in chronic wounds and to develop novel diagnostic tools as well as treatment strategies.

  15. A stochastic model of vaccine trials for endemic infections using group randomization.

    PubMed Central

    Riggs, T. W.; Koopman, J. S.

    2004-01-01

    To clarify the determinants of vaccine trial power for non-typable Haemophilus influenzae, we constructed stochastic SIS models of infection transmission in small units (e.g. day-care centres) to calculate the equilibrium distribution of the number infected. We investigated how unit size, contact rate (modelled as a function of the unit size), external force of infection and infection duration affected the statistical power for detection of vaccine effects on susceptibility or infectiousness. Given a frequency-dependent contact rate, the prevalence, proportion of infections generated internally and the power to detect vaccine effects each increased slightly with unit size. Under a density-dependent model, unit size had much stronger effects. To maximize information allowing inference from vaccine trials, contact functions should be empirically evaluated by studying units of differing size and molecular methods should be used to help distinguish internal vs. external transmission. PMID:15473157

  16. Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

    PubMed

    Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-ichi; Sumitomo, Shinichiro

    2015-12-01

    Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. PMID:26602450

  17. On the time to reach a critical number of infections in epidemic models with infective and susceptible immigrants.

    PubMed

    Almaraz, E; Gómez-Corral, A; Rodríguez-Bernal, M T

    2016-06-01

    In this paper we examine the time T to reach a critical number K0 of infections during an outbreak in an epidemic model with infective and susceptible immigrants. The underlying process X, which was first introduced by Ridler-Rowe (1967), is related to recurrent diseases and it appears to be analytically intractable. We present an approximating model inspired from the use of extreme values, and we derive formulae for the Laplace-Stieltjes transform of T and its moments, which are evaluated by using an iterative procedure. Numerical examples are presented to illustrate the effects of the contact and removal rates on the expected values of T and the threshold K0, when the initial time instant corresponds to an invasion time. We also study the exact reproduction number Rexact,0 and the population transmission number Rp, which are random versions of the basic reproduction number R0. PMID:27068519

  18. Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth

    PubMed Central

    Adams Waldorf, Kristina M.; Rubens, Craig E.; Gravett, Michael G.

    2010-01-01

    Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits, or sheep, demonstrate the key link between infection and premature birth, but differ in mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed emphasizing the role of infections, and potential development of preventative and therapeutic strategies. PMID:21040390

  19. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  20. A model for predicting nosocomial carbapenem-resistant Klebsiella pneumoniae infection

    PubMed Central

    Yang, Duo; Xie, Zeqiang; Xin, Xuli; Xue, Wenying; Zhang, Man

    2016-01-01

    Mortality associated with infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) is high and the infections need to be predicted early. The risk factors for CR-KP infection are heterogeneous. The aim of the present study was to construct a model allowing for the early prediction of CR-KP infection. Nosocomial infections due to K. pneumoniae were evaluated retrospectively over a 2-year period. The case cohort consisted of 370 inpatients with CR-KP infection. For each case enrolled, two matched controls with no CR-KP infection during their hospitalization were randomly selected. Matching involved month of admission, ward, as well as interval days. The Vitek 2 system was used for identification of isolates and antimicrobial susceptibility testing. General linear model with logistic regression was used to identify possible risk factors. The predicted power of the model was expressed as the area under the receiver-operating characteristic curve. Age, male gender, with cardiovascular disease, hospital stay, recent admission to intensive care unit, indwelling urinary catheter, mechanical ventilation, recent β-lactam-β-lactamase inhibitors, fourth-generation cephalosporins and/or carbapenems therapy were independent risk factors for CR-KP infection. Models predicting CR-KP infection developed by cumulative risk factors exhibited good power, with areas under the receiver-operating characteristic curves of 0.902 [95% confidence interval (CI), 0.883–0.920; P<0.001] and 0.899 (95% CI, 0.877–0.921; P<0.001) after filtering by age (≥70 years). The Yonden index was at the maximum when the cumulative risk factors were ≥3 in the two prediction models. The results show that the prediction model developed in the present study might be useful for controlling infections caused by CR-KP strains.

  1. Age-structured dynamic, stochastic and mechanistic simulation model of Salmonella Dublin infection within dairy herds.

    PubMed

    Nielsen, Liza Rosenbaum; Kudahl, Anne Braad; Østergaard, Søren

    2012-06-01

    In the demand for a decision support tool to guide farmers wanting to control Salmonella Dublin (S. Dublin) in Danish dairy herds, we developed an age-structured stochastic, mechanistic and dynamic simulation model of S. Dublin in dairy herds, which incorporated six age groups (neonatal, preweaned calves, weaned calves, growing heifers, breeding heifers and cows) and five infection states (susceptible, acutely infected, carrier, super shedder and resistant). The model simulated population and infection dynamics over a period of 10 years in weekly time steps as: 1) population sizes of each of the six age-groups; 2) S. Dublin incidence and number of animals in each infection state; and 3) S. Dublin related morbidity and mortality in the acutely infected animals. The effects of introducing one infectious heifer on the risk of spread of S. Dublin within the herd and on the duration of infection were estimated through 1000 simulation iterations for 48 scenarios. The scenarios covered all combinations of three herd sizes (70, 200 and 400 cows), four hygiene levels indicating infectious contact parameters, and four herd susceptibility levels indicating different susceptibility parameters for the individual animals in each of the six age groups in the herd. The hygiene level was highly influential on the probability that the infection spread within the herd, duration of infection and epidemic size. The herd susceptibility level was also influential, but not likely to provide sufficient prevention and control of infection on its own. Herd size did not affect the probability of infection spread upon exposure, but the larger the herd the more important were management and housing practices that improve hygiene and reduce susceptibility to shorten durations of infection in the herd and to increase the probability of extinction. In general, disease and mortality patterns followed epidemic waves in the herds. However, an interesting pattern was seen for acute infections and

  2. Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

    NASA Astrophysics Data System (ADS)

    Manna, Kalyan; Chakrabarty, Siddhartha P.

    2015-05-01

    We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

  3. Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks.

    PubMed

    Cai, Chao-Ran; Wu, Zhi-Xi; Chen, Michael Z Q; Holme, Petter; Guan, Jian-Yue

    2016-06-24

    The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches-the heterogeneous mean-field theory and the effective degree method-we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.

  4. Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks

    NASA Astrophysics Data System (ADS)

    Cai, Chao-Ran; Wu, Zhi-Xi; Chen, Michael Z. Q.; Holme, Petter; Guan, Jian-Yue

    2016-06-01

    The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches—the heterogeneous mean-field theory and the effective degree method—we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.

  5. Development of a Mouse Model of Helicobacter pylori Infection that Mimics Human Disease

    NASA Astrophysics Data System (ADS)

    Marchetti, Marta; Arico, Beatrice; Burroni, Daniela; Figura, Natale; Rappuoli, Rino; Ghiara, Paolo

    1995-03-01

    The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.

  6. Epineurium-mimicking chitosan conduits for peripheral nervous tissue engineering.

    PubMed

    Nawrotek, Katarzyna; Tylman, Michał; Rudnicka, Karolina; Gatkowska, Justyna; Wieczorek, Marek

    2016-11-01

    In this investigation, we report on a fabrication method of epineurium-mimicking tubular conduits based on electrodeposition from chitosan solution. The pre-enrichment of electrodeposition solution with hyaluronic acid and/or collagen components results in structures which structural, morphological, and physicochemical properties can be controlled. In order to determine the optimal composition of the initial chitosan solution resulting in conduits meeting the requirements imposed on peripheral nerve implants, we perform chemical, physical, and biological studies. Both the molecular weight of hyaluronic acid and the concentration of additives are found to be crucial for the final mechanical as well as biological performance of conduits. Because, the obtained structures show biocompatibility when contacting with a mouse hippocampal cell line (mHippoE-18), we further plan to test their application potential on an animal model. PMID:27516256

  7. Horizon closeness bounds for static black hole mimickers

    NASA Astrophysics Data System (ADS)

    Sushkov, Sergey V.; Zaslavskii, Oleg B.

    2009-03-01

    We consider the question whether a wormhole can be converted into a nonextremal quasiblack hole by a continuous change of parameters. In other words, we ask whether “black” wormholes can exist as end points of families of static wormhole geometries. The answer is negative since the corresponding limit is singular. Similar conclusions are valid also for other types of black hole mimickers. Our treatment is model independent and applies to any static geometries. We also find an asymptotic expression for the Kretschmann scalar for wormholes on the threshold of horizon formation. We point out complementarity between the ability of wormholes to mimic black holes and their ability to be traversable “in practice.”

  8. Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages

    PubMed Central

    Pawelek, Kasia A.; Dor, Daniel; Salmeron, Cristian; Handel, Andreas

    2016-01-01

    The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics. PMID:26918620

  9. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

    PubMed Central

    Slavuljica, Irena; Kveštak, Daria; Csaba Huszthy, Peter; Kosmac, Kate; Britt, William J; Jonjić, Stipan

    2015-01-01

    Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8+ T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed. PMID:25042632

  10. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model.

    PubMed

    Slavuljica, Irena; Kveštak, Daria; Huszthy, Peter Csaba; Kosmac, Kate; Britt, William J; Jonjić, Stipan

    2015-03-01

    Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8(+) T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.

  11. Hypoglycemia and hyperinsulinemia in rodent models of severe malaria infection.

    PubMed Central

    Elased, K; Playfair, J H

    1994-01-01

    Severe hypoglycemia developed during nonlethal Plasmodium chabaudi and lethal P. yoelii blood stage malaria infection in mice, always in association with hyperinsulinemia. Supernatants of lethal P. yoelii incubated overnight induced hypoglycemia and hyperinsulinemia in normal mice. In murine malaria, hypoglycemia may be largely secondary to increased insulin secretion. PMID:7927799

  12. Anti-infection activity of nanostructured titanium percutaneous implants with a postoperative infection model

    NASA Astrophysics Data System (ADS)

    Tan, Jing; Li, Yiting; Liu, Zhiyuan; Qu, Shuxin; Lu, Xiong; Wang, Jianxin; Duan, Ke; Weng, Jie; Feng, Bo

    2015-07-01

    The titanium percutaneous implants were widely used in clinic; however, they have an increased risk of infection since they breach the skin barrier. Lack of complete skin integration with the implants can cause infection and implant removal. In this work, three titania nanotubes (TNT) with different diameters, 50 nm (TNT-50), 100 nm (TNT-100) and 150 nm (TNT-150) arrays were prepared on titanium surfaces by anodization, pure titanium (pTi) was used as control. Samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle analysis. The antibacterial efficiency of TNT was evaluated in vitro against Staphylococcus aureus under the visible light. The results indicated that TNT-100 had the highest antibacterial efficiency under the visible light. Subsequently, TNT implants and pTi implants were placed subcutaneously to the dorsum of New Zealand White rabbits, 108 CFU S. aureus was inoculated into the implant sites 4 h after surgery. The TNF-alpha and IL-1alpha were determined using enzyme linked immunoassay (ELISA). TNT implants revealed less inflammatory factor release than pTi implants with or without injected S. aureus liquid. According to the histological results, the TNT implants displayed excellent tissue integration. Whereas, pTi implants were surrounded with fibrotic capsule, and the skin tissue was almost separated from the implant surface. Therefore, the TNT significantly inhibited the infection risk and enhanced tissue integration of the percutaneous implants compared to pTi. The immersion test in the culture medium suggested that one of causes be probably more proteins adsorbed on TNT than on pTi.

  13. Characterization of a murine model of intranasal infection suitable for testing vaccines against C. abortus.

    PubMed

    Buendía, A J; Nicolás, L; Ortega, N; Gallego, M C; Martinez, C M; Sanchez, J; Caro, M R; Navarro, J A; Salinas, J

    2007-01-15

    Mouse models have been widely used to test candidate vaccines against Chlamydophila abortus infection in mice. Although the induction of a systemic infection by endogenous or intraperitoneal inoculation is a useful tool for understanding the immune mechanism involved in the protection conferred by the vaccination, a different approach is necessary to understand other factors of the infection, such as mucosal immunity or the colonization of target organs. To test whether C. abortus intranasal model of infection in mice is a useful tool for testing vaccines in a first group of experiments mice, were infected intranasally with C. abortus to characterize the model of infection. When this model was used to test vaccines, two inactivated experimental vaccines, one of them adjuvated with QS-21 and another with aluminium hydroxide, and a live attenuated vaccine (strain 1B) were used. Non-vaccinated control mice died within the first 8 days, after displaying substantial loss of weight. Histologically, the mice showed lobar fibrinopurulent bronchointerstitial pneumonia. Prior immunization with QS-21 adjuvated vaccine or 1B vaccine presented mortality and the recipients showed a greater number of T cells in the lesions, especially CD8(+) T cells, than the control mice and mice immunized with vaccine adjuvated with aluminium hydroxide. The results confirm that the C. abortus intranasal model of infection in mice is a useful tool for testing vaccines.

  14. Lethal infection by Bordetella pertussis mutants in the infant mouse model.

    PubMed Central

    Weiss, A A; Goodwin, M S

    1989-01-01

    Different aspects of lethal infection of infant mice with Bordetella pertussis were examined. Mutants deficient in vir-regulated genes were tested for the ability to cause a lethal infection in the infant mouse model. Adenylate cyclase toxin-hemolysin and pertussis toxin were required to cause a lethal infection at low doses. Mixed infection caused by challenging the mice with an equal number of pertussis toxin and adenylate cyclase toxin-hemolysin mutants at a dose at which neither alone was lethal was also unable to cause a lethal infection. Production of the filamentous hemagglutinin and the dermonecrotic toxin was not required to cause a lethal infection. Nine other mutants in vir-regulated genes whose phenotypes have yet to be determined were also tested. Only two of these mutants were impaired in the ability to cause a lethal infection. Expression of fimbriae does not appear to affect the dose required to cause a lethal infection; however, fimbrial expression was correlated with the later stages of a nonlethal, persistent infection. Growth of the bacteria in MgSO4, a condition which reversibly suppresses expression of the genes required for virulence, did not alter the ability of the bacteria to cause a lethal infection. Auxotrophic mutants deficient in leucine biosynthesis were as virulent as the parental strain; however, mutants deficient in methionine biosynthesis were less virulent. A B. parapertussis strain was much less effective in promoting a lethal infection than any of the wild-type B. pertussis strains examined. A persistent infection in the lungs was observed for weeks after challenge for mice given a sublethal dose of B. pertussis, and transmission from infected infants to the mother was never observed. PMID:2572561

  15. A framework for the joint modeling of longitudinal diagnostic outcome data and latent infection status: application to investigating the temporal relationship between infection and disease.

    PubMed

    Jones, G; Johnson, W O; Vink, W D; French, N

    2012-06-01

    For many diseases the infection status of individuals cannot be observed directly, but can only be inferred from biomarkers that are subject to measurement error. Diagnosis of infection based on observed symptoms can itself be regarded as an imperfect test of infection status. The temporal relationship between infection and marker outcomes may be complex, especially for recurrent diseases where individuals can experience multiple bouts of infection. We propose an approach that first models the unobserved longitudinal infection status of individuals conditional on relevant covariates, and then jointly models the longitudinal sequence of biomarker outcomes conditional on infection status and covariate information through time, thus resulting in a joint model for longitudinal infection and biomarker sequences. This model can be used to investigate the temporal dynamics of infection, and to evaluate the usefulness of biomarkers for monitoring purposes. Our work is motivated and illustrated by a longitudinal study of bovine digital dermatitis (BDD) on commercial dairy farms in North West England and North Wales, in which the infection of interest is Treponeme spp., and the biomarkers of interest are a continuous enzyme-linked immunosorbent assay test outcome and a dichotomous outcome, foot lesion status. BDD is known to be one of the possible causes of foot lesions in cows.

  16. A co-infection model of malaria and cholera diseases with optimal control.

    PubMed

    Okosun, K O; Makinde, O D

    2014-12-01

    In this paper we formulate a mathematical model for malaria-cholera co-infection in order to investigate their synergistic relationship in the presence of treatments. We first analyze the single infection steady states, calculate the basic reproduction number and then investigate the existence and stability of equilibria. We then analyze the co-infection model, which is found to exhibit backward bifurcation. The impact of malaria and its treatment on the dynamics of cholera is further investigated. Secondly, we incorporate time dependent controls, using Pontryagin's Maximum Principle to derive necessary conditions for the optimal control of the disease. We found that malaria infection may be associated with an increased risk of cholera but however, cholera infection is not associated with an increased risk for malaria. Therefore, to effectively control malaria, the malaria intervention strategies by policy makers must at the same time also include cholera control.

  17. Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model.

    PubMed

    Beeton, M L; Alves, D R; Enright, M C; Jenkins, A T A

    2015-08-01

    The Galleria mellonella infection model was used to assess the in vivo efficacy of phage therapy against laboratory and clinical strains of Pseudomonas aeruginosa. In a first series of experiments, Galleria were infected with the laboratory strain P. aeruginosa PAO1 and were treated with varying multiplicity of infection (MOI) of phages either 2h post-infection (treatment) or 2h pre-infection (prevention) via injection into the haemolymph. To address the kinetics of infection, larvae were bled over a period of 24h for quantification of bacteria and phages. Survival rates at 24h when infected with 10 cells/larvae were greater in the prevention versus treatment model (47% vs. 40%, MOI=10; 47% vs. 20%, MOI=1; and 33% vs. 7%, MOI=0.1). This pattern held true when 100 cells/larvae were used (87% vs. 20%, MOI=10; 53% vs. 13%, MOI=1; 67% vs. 7%, MOI=0.1). By 24h post-infection, phages kept bacterial cell numbers in the haemolymph 1000-fold lower than in the non-treated group. In a second series of experiments using clinical strains to further validate the prevention model, phages protected Galleria when infected with both a bacteraemia (0% vs. 85%) and a cystic fibrosis (80% vs. 100%) isolate. Therefore, this study validates the use of G. mellonella as a simple, robust and cost-effective model for initial in vivo examination of P. aeruginosa-targeted phage therapy, which may be applied to other pathogens with similarly low infective doses. PMID:26100212

  18. The chicken as a natural model for extraintestinal infections caused by avian pathogenic Escherichia coli (APEC).

    PubMed

    Antão, Esther-Maria; Glodde, Susanne; Li, Ganwu; Sharifi, Reza; Homeier, Timo; Laturnus, Claudia; Diehl, Ines; Bethe, Astrid; Philipp, Hans-C; Preisinger, Rudolf; Wieler, Lothar H; Ewers, Christa

    2008-01-01

    E. coli infections in avian species have become an economic threat to the poultry industry worldwide. Several factors have been associated with the virulence of E. coli in avian hosts, but no specific virulence gene has been identified as being entirely responsible for the pathogenicity of avian pathogenic E. coli (APEC). Needless to say, the chicken would serve as the best model organism for unravelling the pathogenic mechanisms of APEC, an extraintestinal pathogen. Five-week-old white leghorn SPF chickens were infected intra-tracheally with a well characterized APEC field strain IMT5155 (O2:K1:H5) using different doses corresponding to the respective models of infection established, that is, the lung colonization model allowing re-isolation of bacteria only from the lung but not from other internal organs, and the systemic infection model. These two models represent the crucial steps in the pathogenesis of APEC infections, including the colonization of the lung epithelium and the spread of bacteria throughout the bloodstream. The read-out system includes a clinical score, pathomorphological changes and bacterial load determination. The lung colonization model has been established and described for the first time in this study, in addition to a comprehensive account of a systemic infection model which enables the study of severe extraintestinal pathogenic E. coli (ExPEC) infections. These in vivo models enable the application of various molecular approaches to study host-pathogen interactions more closely. The most important application of such genetic manipulation techniques is the identification of genes required for extraintestinal virulence, as well as host genes involved in immunity in vivo. The knowledge obtained from these studies serves the dual purpose of shedding light on the nature of virulence itself, as well as providing a route for rational attenuation of the pathogen for vaccine construction, a measure by which extraintestinal infections, including

  19. A Case of Multi-vector and Multi-host Epidemiological Model: Bartonella Infection

    NASA Astrophysics Data System (ADS)

    Anguelov, R.; Brettschneider, H.; Bastos, A. D. S.

    2010-11-01

    We consider a compartmental model for the Bartonella infection on rodents. More precisely, on the co-occurring populations of Rattus rattus and Rattus norvegicus where the vectors are two species of ectoparasites, namely ticks and fleas. As usual for such models a key stage is the modelling of the forces of infection. While the vital dynamics and the progression of the infection within each of the four species are sufficiently well known to determine the rest of the transfer rates, there is practically no data on the probability of infection. In order to determine appropriate values for the coefficients of the forces of infection we solve an optimal control problem where the objective function is the norm of the difference between the observed and the predicted by the model equilibrium infection prevalence rates in the four species. Within this setting the conjecture that the higher prevalence of the infection in Rattus norvegicus can be explained solely by their higher ectoparasite load is tested and disproved.

  20. Mad honey poisoning mimicking acute myocardial infarction.

    PubMed

    Chen, Sammy P L; Lam, Y H; Ng, Vember C H; Lau, F L; Sze, Y C; Chan, W T; Mak, Tony W L

    2013-08-01

    We report a case of acute poisoning in a 48-year-old man who presented with chest pain, abdominal pain, dizziness, sweatiness, blurred vision, and severe hypotension after ingestion of honey. His electrocardiogram showed sinus bradycardia and transient ST elevation. He made a good recovery after treatment with atropine and close monitoring. Grayanotoxin was detected in his urine and the honey he ingested, which confirmed a diagnosis of mad honey poisoning. This is a condition prevalent in the Black Sea region around Turkey but rarely seen locally. Although mad honey poisoning is life-threatening, early use of atropine is life-saving. Such poisoning may present with ST elevation in the electrocardiogram and symptoms mimicking acute myocardial infarction. It is therefore essential for clinicians to recognise this unusual form of poisoning and avoid the disastrous use of thrombolytic therapy.

  1. Orthokeratinised odontogenic cyst mimicking periapical cyst.

    PubMed

    Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

    2013-01-01

    Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth. PMID:24099763

  2. Orthokeratinised odontogenic cyst mimicking periapical cyst

    PubMed Central

    Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

    2013-01-01

    Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth. PMID:24099763

  3. Case report. Pityriasis versicolor mimicking Pityriasis rotunda.

    PubMed

    Aste, Nicola; Pau, Monica; Aste, Natalia; Biggio, P

    2002-04-01

    Pityriasis versicolor is a common dermatomycosis, occurring throughout the world, characterized by irregular, slightly scaly patches, varying in color from red/light brown to white. Pityriasis rotunda, on the other hand, is an uncommon disease, reported in specific ethnic groups, and characterized by perfectly round or oval patches of varying color, with a scaly surface. The histologic pattern is that of ichthyosis vulgaris. We report here the case of a male patient, aged 31, from Sardinia (Italy), affected by Pityriasis versicolor mimicking Pityriasis rotunda. Mycological examination allowed us to formulate the correct diagnosis, and ensuing treatment with antifungal drugs was entirely successful. The authors, while pointing out the rarity of this case, stress the possibility that Pityriasis versicolor mimics Pityriasis rotunda and vice-versa, especially in those countries in which the two diseases are endemic. More widespread recourse to microscopic examination can help avoid the risk of mistaken diagnosis and consequent incorrect treatment.

  4. A subtle mimicker in emergency department

    PubMed Central

    Angelis, Maria Vittoria De; Giacomo, Roberta Di; Muzio, Antonio Di; Onofrj, Marco; Bonanni, Laura

    2016-01-01

    Abstract Background: Movement disorder emergencies include any movement disorder which develops over hours to days, in which failure to appropriately diagnose and manage can result in patient morbidity or mortality. Movement disorder emergencies include acute dystonia: sustained or intermittent muscle contractions causing abnormal, often repetitive, movements. Acute dystonia is a serious challenge for emergency room doctors and neurologists, because of the high probability of misdiagnosis, due to the presence of several mimickers including partial seizures, meningitis, localized tetanus, serum electrolyte level abnormalities, strychnine poisoning, angioedema, malingering, catatonia, and conversion. Methods: We describe 2 examples, accompanied by videos, of acute drug-induced oro-mandibular dystonia, both subsequent to occasional haloperidol intake. Results: Management and treatment of this movement disorder are often difficult: neuroleptics withdrawal, treatment with benzodiazepines, and anticholinergics are recommended. Conclusion: Alternative treatment options are also discussed. PMID:27741141

  5. Retroperitoneal bronchogenic cyst mimicking pancreatic cystic lesion.

    PubMed

    Wang, Shin-E; Tsai, Yi-Fang; Su, Cheng-Hsi; Shyr, Yi-Ming; Lee, Rheun-Chuan; Tsai, Wan-Chen; Li, Fen-Yau; Chen, Tien-Hua; Wu, Chew-Wun; Lui, Wing-Yiu

    2006-11-01

    Retroperitoneal bronchogenic cyst is detected extremely rarely and often masquerades as other diseases. Here, we report 2 cases of retroperitoneal bronchogenic cyst mimicking pancreatic mucinous tumor. Histologically, both cysts were composed of ciliated respiratory-like epithelium with abundant mucin content, smooth muscle bundles and mature cartilage, compatible with the diagnosis of retroperitoneal bronchogenic cyst. In addition to these 2 cases, another 42 retroperitoneal bronchogenic cysts reported in the English literature were collected for review and analysis. Twelve (28%) were located over the peripancreatic area. Just over half (51%) of them were asymptomatic. No accurate preoperative diagnosis could be made for any of the lesions. About a third (33.3%) of the peripancreatic retroperitoneal bronchogenic cysts masqueraded as pancreatic cystic lesions.

  6. Peripheral effects induced in BALB/c mice infected with DENV by the intracerebral route.

    PubMed

    Oliveira, E R A; Amorim, J F S; Paes, M V; Azevedo, A S; Gonçalves, A J S; Costa, S M; Mantuano-Barradas, M; Póvoa, T F; de Meis, J; Basílio-de-Oliveira, C A; Nogueira, A C M A; Alves, A M B

    2016-02-01

    The lack of an immunocompetent animal model for dengue mimicking the disease in humans is a limitation for advances in this field. Inoculation by intracerebral route of neuroadapted dengue strains in mice is normally lethal and provides a straightforward readout parameter for vaccine testing. However, systemic effects of infection and the immune response elicited in this model remain poorly described. In the present work, BALB/c mice infected by the intracerebral route with neuroadapted DENV2 exhibited several evidences of systemic involvement. DENV-inoculated mice presented virus infective particles in the brain followed by viremia, especially in late stages of infection. Infection induced cellular and humoral responses, with presence of activated T cells in spleen and blood, lymphocyte infiltration and tissue damages in brain and liver, and an increase in serum levels of some pro-inflammatory cytokines. Data highlighted an interplay between the central nervous system commitment and peripheral effects under this experimental condition. PMID:26748331

  7. An agent-based model for Leishmania major infection

    NASA Astrophysics Data System (ADS)

    Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.

    Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if left untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].

  8. An agent-based model for Leishmania major infection

    NASA Astrophysics Data System (ADS)

    Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.

    Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].

  9. A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections

    PubMed Central

    2013-01-01

    Background Implant infection is one of the most severe complications within the field of orthopaedic surgery, associated with an enormous burden for the healthcare system. During the last decades, attempts have been made to lower the incidence of implant-related infections. In the case of cemented prostheses, the use of antibiotic-containing bone cement can be effective. However, in the case of non-cemented prostheses, osteosynthesis and spinal surgery, local antibacterial prophylaxis is not a standard procedure. For the development of implant coatings with antibacterial properties, there is a need for a reliable animal model to evaluate the preventive capacity of such coatings during a specific period of time. Existing animal models generally present a limited follow-up, with a limited number of outcome parameters and relatively large animal numbers in multiple groups. Methods To represent an early post-operative implant infection, we established an acute tibial intramedullary nail infection model in rabbits by contamination of the tibial nail with 3.8 × 105 colony forming units of Staphylococcus aureus. Clinical, haematological and radiological parameters for infection were weekly assessed during a 6-week follow-up with post-mortem bacteriological and histological analyses. Results S. aureus implant infection was confirmed by the above parameters. A saline control group did not develop osteomyelitis. By combining the clinical, haematological, radiological, bacteriological and histological data collected during the experimental follow-up, we were able to differentiate between the control and the infected condition and assess the severity of the infection at sequential timepoints in a parameter-dependent fashion. Conclusion We herein present an acute early post-operative rabbit implant infection model which, in contrast to previously published models, combines improved in-time insight into the development of an implant osteomyelitis with a relatively low

  10. Activation of innate immune responses in a pathogen-mimicking manner by amphiphilic polyanhydride nanoparticle adjuvants.

    PubMed

    Petersen, Latrisha K; Ramer-Tait, Amanda E; Broderick, Scott R; Kong, Chang-Sun; Ulery, Bret D; Rajan, Krishna; Wannemuehler, Michael J; Narasimhan, Balaji

    2011-10-01

    Techniques in materials design, immunophenotyping, and informatics can be valuable tools for using a molecular based approach to design vaccine adjuvants capable of inducing protective immunity that mimics a natural infection but without the toxic side effects. This work describes the molecular design of amphiphilic polyanhydride nanoparticles that activate antigen presenting cells in a pathogen-mimicking manner. Biodegradable polyanhydrides are well suited as vaccine delivery vehicles due to their adjuvant-like ability to: 1) enhance the immune response, 2) preserve protein structure, and 3) control protein release. The results of these studies indicate that amphiphilic nanoparticles possess pathogen-mimicking properties as evidenced by their ability to activate dendritic cells similarly to LPS. Specific molecular descriptors responsible for this behavior were identified using informatics analyses, including the number of backbone oxygen moieties, percent of hydroxyl end groups, polymer hydrophobicity, and number of alkyl ethers. Additional findings from this work suggest that the molecular characteristics mediating APC activation are not limited to hydrophobicity but vary in complexity (e.g., presentation of oxygen-rich molecular patterns to cells) and elicit unique patterns of cellular activation. The approach outlined herein demonstrates the ability to rationally design pathogen-mimicking nanoparticle adjuvants for use in next-generation vaccines against emerging and re-emerging diseases.

  11. Global Analysis of Viral Infection in an Archaeal Model System

    PubMed Central

    Maaty, Walid S.; Steffens, Joseph D.; Heinemann, Joshua; Ortmann, Alice C.; Reeves, Benjamin D.; Biswas, Swapan K.; Dratz, Edward A.; Grieco, Paul A.; Young, Mark J.; Bothner, Brian

    2012-01-01

    The origin and evolutionary relationship of viruses is poorly understood. This makes archaeal virus-host systems of particular interest because the hosts generally root near the base of phylogenetic trees, while some of the viruses have clear structural similarities to those that infect prokaryotic and eukaryotic cells. Despite the advantageous position for use in evolutionary studies, little is known about archaeal viruses or how they interact with their hosts, compared to viruses of bacteria and eukaryotes. In addition, many archaeal viruses have been isolated from extreme environments and present a unique opportunity for elucidating factors that are important for existence at the extremes. In this article we focus on virus-host interactions using a proteomics approach to study Sulfolobus Turreted Icosahedral Virus (STIV) infection of Sulfolobus solfataricus P2. Using cultures grown from the ATCC cell stock, a single cycle of STIV infection was sampled six times over a 72 h period. More than 700 proteins were identified throughout the course of the experiments. Seventy one host proteins were found to change their concentration by nearly twofold (p < 0.05) with 40 becoming more abundant and 31 less abundant. The modulated proteins represent 30 different cell pathways and 14 clusters of orthologous groups. 2D gel analysis showed that changes in post-translational modifications were a common feature of the affected proteins. The results from these studies showed that the prokaryotic antiviral adaptive immune system CRISPR-associated proteins (CAS proteins) were regulated in response to the virus infection. It was found that regulated proteins come from mRNAs with a shorter than average half-life. In addition, activity-based protein profiling (ABPP) profiling on 2D-gels showed caspase, hydrolase, and tyrosine phosphatase enzyme activity labeling at the protein isoform level. Together, this data provides a more detailed global view of archaeal cellular responses

  12. Asymptotic profiles of steady states for a diffusive SIS epidemic model with mass action infection mechanism

    NASA Astrophysics Data System (ADS)

    Wu, Yixiang; Zou, Xingfu

    2016-10-01

    Mass action and standard incidence are two major infection mechanisms in modelling spread of infectious diseases. Spatial heterogeneity plays an important role in spread of infectious diseases, and hence, motivates and advocates diffusive models for disease dynamics. By analyzing a diffusive SIS model with the standard incidence infection mechanism, some recent works [2,12] have investigated the asymptotical profiles of the endemic steady state for large and small diffusion rates, and the results show that controlling the diffusion rate of the susceptible individuals can help eradicate the infection, while controlling the diffusion rate of the infectious individuals cannot. This paper aims to reveal the difference between the two infection mechanisms in a spatially heterogeneous environment. To this end, we consider a diffusive SIS model of the same structure but with the mass action infection adopted, and explore the asymptotic profiles of the endemic steady state for small and large diffusion rates. It turns out that the new model poses some new challenges due to the nonlocal term in the equilibrium problem and the unboundedness of the nonlinear term. Our results on this new model reveal some fundamental differences between the two transmission mechanisms in such spatial models, which may provide some implications on disease modelling and controls.

  13. A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus

    PubMed Central

    Shelite, Thomas R.; Saito, Tais B.; Mendell, Nicole L.; Gong, Bin; Xu, Guang; Soong, Lynn; Valbuena, Gustavo; Bouyer, Donald H.; Walker, David H.

    2014-01-01

    Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25×106 focus (FFU) forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection. PMID:25010338

  14. Development of an Aeromonas hydrophila  infection model using the protozoan Tetrahymena thermophila.

    PubMed

    Li, Jing; Zhang, Xiao-Lu; Liu, Yong-Jie; Lu, Cheng-Ping

    2011-03-01

    Aeromonas hydrophila is a motile bacterium present in numerous freshwater habitats worldwide and is frequently the cause of infections in fish and numerous terrestrial vertebrates including humans. Because A. hydrophila is also a component of the normal intestinal flora of healthy fish, virulence mechanisms are not well understood. Considering that fish models used for the examination of A. hydrophila genes associated with virulence have not been well defined, we established an infection model using the free-living, ciliate protozoa Tetrahymena thermophila. The expression of A. hydrophila virulence genes following infection of T. thermophila was assessed by reverse transcription-PCR and demonstrated that the aerolysin (aerA) and Ahe2 serine protease (ahe2) genes (not present in the avirulent A. hydrophila NJ-4 strain) in the virulent J-1 strain were upregulated 4-h postinfection. Furthermore, the presence of intact A. hydrophila J-1 within T. thermophila suggested that these bacteria could interfere with phagocytosis, resulting in the death of the infected protozoan 48-h postinfection. Conversely, A. hydrophila NJ-4-infected T. thermophila survived the infection. This study established a novel T. thermophila infection model that will provide a novel means of examining virulence mechanisms of A. hydrophila.

  15. Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations

    PubMed Central

    2012-01-01

    Background The persistence of bovine TB (bTB) in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles). The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model. Results The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6–8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone. Conclusions External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to reduce bTB in badgers include

  16. Experimental in vitro and in vivo models for the study of human hepatitis B virus infection.

    PubMed

    Allweiss, Lena; Dandri, Maura

    2016-04-01

    Chronic infection with the hepatitis B virus (HBV) affects an estimate of 240 million people worldwide despite the availability of a preventive vaccine. Medication to repress viral replication is available but a cure is rarely achieved. The narrow species and tissue tropism of the virus and the lack of reliable in vitro models and laboratory animals susceptible to HBV infection, have limited research progress in the past. As a result, several aspects of the HBV life cycle as well as the network of virus host interactions occurring during the infection are not yet understood. Only recently, the identification of the functional cellular receptor enabling HBV entry has opened new possibilities to establish innovative infection systems. Regarding the in vivo models of HBV infection, the classical reference was the chimpanzee. However, because of the strongly restricted use of great apes for HBV research, major efforts have focused on the development of mouse models of HBV replication and infection such as the generation of humanized mice. This review summarizes the animal and cell culture based models currently available for the study of HBV biology. We will discuss the benefits and caveats of each model and present a selection of the most important findings that have been retrieved from the respective systems. PMID:27084033

  17. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry.

    PubMed

    Lin, Qingqing; London, Erwin

    2014-01-01

    Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes "artificial plasma membrane mimicking" ("PMm") vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

  18. A Pre-clinical Animal Model of Trypanosoma brucei Infection Demonstrating Cardiac Dysfunction.

    PubMed

    McCarroll, Charlotte S; Rossor, Charlotte L; Morrison, Linda R; Morrison, Liam J; Loughrey, Christopher M

    2015-05-01

    African trypanosomiasis (AT), caused by Trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. Research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias) in AT remains largely unstudied. Animal models of AT demonstrating cardiac dysfunction similar to that described in field cases of AT are critically required to transform our understanding of AT-induced cardiac pathophysiology and identify future treatment strategies. We have previously shown that T. brucei can interact with heart muscle cells (cardiomyocytes) to induce ventricular arrhythmias in ex vivo adult rat hearts. However, it is unknown whether the arrhythmias observed ex vivo are also present during in vivo infection in experimental animal models. Here we show for the first time the characterisation of ventricular arrhythmias in vivo in two animal models of AT infection using electrocardiographic (ECG) monitoring. The first model utilised a commonly used monomorphic laboratory strain, Trypanosoma brucei brucei Lister 427, whilst the second model used a pleomorphic laboratory strain, T. b. brucei TREU 927, which demonstrates a similar chronic infection profile to clinical cases. The frequency of ventricular arrhythmias and heart rate (HR) was significantly increased at the endpoint of infection in the TREU 927 infection model, but not in the Lister 427 infection model. At the end of infection, hearts from both models were isolated and Langendorff perfused ex vivo with increasing concentrations of the β-adrenergic agonist isoproterenol (ISO). Interestingly, the increased frequency of arrhythmias observed in vivo in the TREU 927 infection model was lost upon isolation of the heart ex vivo, but re-emerged with the addition of ISO. Our results demonstrate that TREU 927 infection modifies the substrate of the myocardium in such a way

  19. Relationships between anaemia and parasitic infections in Kenyan schoolchildren: a Bayesian hierarchical modelling approach.

    PubMed

    Koukounari, Artemis; Estambale, Benson B A; Njagi, J Kiambo; Cundill, Bonnie; Ajanga, Anthony; Crudder, Christopher; Otido, Julius; Jukes, Matthew C H; Clarke, Siân E; Brooker, Simon

    2008-12-01

    Anaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10-21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission.

  20. Relationships between anaemia and parasitic infections in Kenyan schoolchildren: A Bayesian hierarchical modelling approach

    PubMed Central

    Koukounari, Artemis; Estambale, Benson B.A.; Kiambo Njagi, J.; Cundill, Bonnie; Ajanga, Anthony; Crudder, Christopher; Otido, Julius; Jukes, Matthew C.H.; Clarke, Siân E.; Brooker, Simon

    2008-01-01

    Anaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10–21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission. PMID:18621051

  1. Propagation dynamics of an epidemic model with infective media connecting two separated networks of populations

    NASA Astrophysics Data System (ADS)

    Zhu, Guanghu; Chen, Guanrong; Zhang, Haifeng; Fu, Xinchu

    2015-01-01

    Based on the fact that most human pathogens originate from animals, this paper attempts to illustrate the propagation dynamics of some zoonotic infections, which spread in two separated networks of populations (human network I and animal network II) and cross-species (vectors, or infective media). An epidemic time-evolution model is proposed via mean-field approximation and its global dynamics are investigated. It is found that the basic reproduction number in terms of epidemiological parameters and the network structure is the threshold condition determining the propagation dynamics. Further, the influences of various infection rates and contact patterns are verified. Numerical results show that the heterogeneity in connection patterns and inner infection in network I can easily trigger endemic dynamics, but when a pathogen, such as H7N9, has weak infectivity in humans, the effects of animal-animal interactions and the contacts with vectors tend to induce endemic states and enhance the prevalence in all the populations.

  2. Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts.

    PubMed

    Brunke, Sascha; Quintin, Jessica; Kasper, Lydia; Jacobsen, Ilse D; Richter, Martin E; Hiller, Ekkehard; Schwarzmüller, Tobias; d'Enfert, Christophe; Kuchler, Karl; Rupp, Steffen; Hube, Bernhard; Ferrandon, Dominique

    2015-05-01

    Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host. PMID:25786415

  3. Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts.

    PubMed

    Brunke, Sascha; Quintin, Jessica; Kasper, Lydia; Jacobsen, Ilse D; Richter, Martin E; Hiller, Ekkehard; Schwarzmüller, Tobias; d'Enfert, Christophe; Kuchler, Karl; Rupp, Steffen; Hube, Bernhard; Ferrandon, Dominique

    2015-05-01

    Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.

  4. Of mice, flies – and men? Comparing fungal infection models for large-scale screening efforts

    PubMed Central

    Brunke, Sascha; Quintin, Jessica; Kasper, Lydia; Jacobsen, Ilse D.; Richter, Martin E.; Hiller, Ekkehard; Schwarzmüller, Tobias; d'Enfert, Christophe; Kuchler, Karl; Rupp, Steffen; Hube, Bernhard; Ferrandon, Dominique

    2015-01-01

    ABSTRACT Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host. PMID:25786415

  5. A comparison of computational efficiencies of stochastic algorithms in terms of two infection models.

    PubMed

    Banks, H Thomas; Hu, Shuhua; Joyner, Michele; Broido, Anna; Canter, Brandi; Gayvert, Kaitlyn; Link, Kathryn

    2012-07-01

    In this paper, we investigate three particular algorithms: a stochastic simulation algorithm (SSA), and explicit and implicit tau-leaping algorithms. To compare these methods, we used them to analyze two infection models: a Vancomycin-resistant enterococcus (VRE) infection model at the population level, and a Human Immunodeficiency Virus (HIV) within host infection model. While the first has a low species count and few transitions, the second is more complex with a comparable number of species involved. The relative efficiency of each algorithm is determined based on computational time and degree of precision required. The numerical results suggest that all three algorithms have the similar computational efficiency for the simpler VRE model, and the SSA is the best choice due to its simplicity and accuracy. In addition, we have found that with the larger and more complex HIV model, implementation and modification of tau-Leaping methods are preferred.

  6. Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model

    PubMed Central

    Achermann, Yvonne; Tran, Bao; Kang, Misun; Harro, Janette M.

    2015-01-01

    Propionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implant-associated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes. PMID:25694647

  7. Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model.

    PubMed

    Achermann, Yvonne; Tran, Bao; Kang, Misun; Harro, Janette M; Shirtliff, Mark E

    2015-05-01

    Propionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implant-associated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes. PMID:25694647

  8. Mycobacterium avium Subspecies paratuberculosis Infection Modifies Gut Microbiota under Different Dietary Conditions in a Rabbit Model

    PubMed Central

    Arrazuria, Rakel; Elguezabal, Natalia; Juste, Ramon A.; Derakhshani, Hooman; Khafipour, Ehsan

    2016-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) the causative agent of paratuberculosis, produces a chronic granulomatous inflammation of the gastrointestinal tract of ruminants. It has been recently suggested that MAP infection may be associated with dysbiosis of intestinal microbiota in ruminants. Since diet is one of the key factors affecting the balance of microbial populations in the digestive tract, we intended to evaluate the effect of MAP infection in a rabbit model fed a regular or high fiber diet during challenge. The composition of microbiota of the cecal content and the sacculus rotundus was studied in 20 New Zealand white female rabbits. The extracted DNA was subjected to paired-end Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene for microbiota analysis. Microbial richness (Chao1) in the cecal content was significantly increased by MAP infection in regular diet rabbits (p = 0.0043) and marginally increased (p = 0.0503) in the high fiber group. Analysis of beta-diversity showed that MAP infection produces deeper changes in the microbiota of sacculus rotundus than in the cecal content. A lower abundance of Proteobacteria in the cecal content of infected animals fed the high fiber diet and also lower abundance of Bacteroidetes in the sacculus rotundus of infected animals fed the regular diet were observed. Based on OPLS-DA analysis, we observed that some bacteria repeatedly appear to be positively associated with infection in different samples under different diets (families Dehalobacteriaceae, Coriobacteriaceae, and Mogibacteriaceae; genus Anaerofustis). The same phenomenon was observed with some of the bacteria negatively associated with MAP infection (genera Anaerostipes and Coprobacillus). However, other groups of bacteria (Enterobacteriaceae family and ML615J-28 order) were positively associated with infection in some circumstances and negatively associated with infection in others. Data demonstrate that MAP infection

  9. An in vivo polymicrobial biofilm wound infection model to study interspecies interactions.

    PubMed

    Dalton, Trevor; Dowd, Scot E; Wolcott, Randall D; Sun, Yan; Watters, Chase; Griswold, John A; Rumbaugh, Kendra P

    2011-01-01

    Chronic wound infections are typically polymicrobial; however, most in vivo studies have focused on monospecies infections. This project was designed to develop an in vivo, polymicrobial, biofilm-related, infected wound model in order to study multispecies biofilm dynamics and in relation to wound chronicity. Multispecies biofilms consisting of both Gram negative and Gram positive strains, as well as aerobes and anaerobes, were grown in vitro and then transplanted onto the wounds of mice. These in vitro-to-in vivo multi-species biofilm transplants generated polymicrobial wound infections, which remained heterogeneous with four bacterial species throughout the experiment. We observed that wounded mice given multispecies biofilm infections displayed a wound healing impairment over mice infected with a single-species of bacteria. In addition, the bacteria in the polymicrobial wound infections displayed increased antimicrobial tolerance in comparison to those in single species infections. These data suggest that synergistic interactions between different bacterial species in wounds may contribute to healing delays and/or antibiotic tolerance.

  10. Mimicking static anisotropic fluid spheres in general relativity

    NASA Astrophysics Data System (ADS)

    Boonserm, Petarpa; Ngampitipan, Tritos; Visser, Matt

    2016-11-01

    We argue that an arbitrary general relativistic static anisotropic fluid sphere, (static and spherically symmetric but with transverse pressure not equal to radial pressure), can nevertheless be successfully mimicked by suitable linear combinations of theoretically attractive and quite simple classical matter: a classical (charged) isotropic perfect fluid, a classical electromagnetic field and a classical (minimally coupled) scalar field. While the most general decomposition is not unique, a preferred minimal decomposition can be constructed that is unique. We show how the classical energy conditions for the anisotropic fluid sphere can be related to energy conditions for the isotropic perfect fluid, electromagnetic field, and scalar field components of the model. Furthermore, we show how this decomposition relates to the distribution of both electric charge density and scalar charge density throughout the model. The generalized TOV equation implies that the perfect fluid component in this model is automatically in internal equilibrium, with pressure forces, electric forces, and scalar forces balancing the gravitational pseudo-force. Consequently, we can build theoretically attractive matter models that can be used to mimic almost any static spherically symmetric spacetime.

  11. Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus.

    PubMed

    Martín, Verónica; Mavian, Carla; López Bueno, Alberto; de Molina, Antonio; Díaz, Eduardo; Andrés, Germán; Alcami, Antonio; Alejo, Alí

    2015-10-01

    Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections.

  12. Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus

    PubMed Central

    Martín, Verónica; Mavian, Carla; López Bueno, Alberto; de Molina, Antonio; Díaz, Eduardo; Andrés, Germán; Alcami, Antonio

    2015-01-01

    Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections. PMID:26246565

  13. Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection

    PubMed Central

    Verrier, Eloi R.; Colpitts, Che C.; Schuster, Catherine; Zeisel, Mirjam B.; Baumert, Thomas F.

    2016-01-01

    Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments. PMID:27657111

  14. Establishment of an aerosol-based Marek's disease virus infection model.

    PubMed

    Abdul-Careem, Mohamed Faizal; Javaheri-Vayeghan, Abbas; Shanmuganathan, Sangitha; Haghighi, Hamid Reza; Read, Leah R; Haq, Kamran; Hunter, D Bruce; Schat, Karel A; Heidari, Mohammad; Sharif, Shayan

    2009-09-01

    Marek's disease virus (MDV), which is the causative agent of Marek's disease (MD), is shed by infected chickens and transmitted to other chickens through the respiratory route. Experimental reproduction of MD has been commonly done either by intra-abdominal inoculation of cell-associated MDV or by exposure to MDV-infected 'seeder' chickens. The former method does not mimic the natural route of MDV infection, whereas the latter method suffers from lack of uniformity in the timing and amount of virus transmission from seeder chickens to susceptible birds. The aim of the present study was to establish an infection model of MDV that mimics the natural route of infection. Here we report that when chickens were exposed for 20 min to aerosols (particle size 1.91 microm) of cell-free MDV suspensions containing 1280 plaque-forming units/ml, which were generated using a nebulizer, pathological and clinical signs of MD were observed in 95%-100% of the aerosol-exposed chickens by 21 days post-infection (dpi). Chickens that were exposed to aerosols and sampled at 1, 2, 3, 10, and 21 dpi showed MDV replication as early as 1 dpi in lungs as well as in other tissues such as spleen and bursa of Fabricius. This infection model will facilitate the studies directed to elucidate MDV-host interaction at the site of virus entry. PMID:19848077

  15. (99m)Tc-MDP- and (18F)-FDG-avid florid reactive periostitis ossificans mimicking recurrent osteosarcoma.

    PubMed

    Byun, Byung Hyun; Koh, Jae-Soo; Yoo, Ji Young; Lim, Sang Moo; Kong, Chang-Bae

    2013-06-01

    Florid reactive periostitis ossificans is a rare benign lesion usually affecting the tubular bones of the hands and feet, and its histological features may be confused with those of infection and osteosarcoma. We report a case with florid reactive periostitis ossificans of the femur showing increased tracer uptake on both Tc-MDP bone scan and F-FDG PET/CT mimicking a local recurrence in a 15-year-old patient with high-grade osteosarcoma.

  16. Development of humanized mouse models to study human malaria parasite infection

    PubMed Central

    Vaughan, Ashley M; Kappe, Stefan HI; Ploss, Alexander; Mikolajczak, Sebastian A

    2013-01-01

    Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future. PMID:22568719

  17. Mathematical Modeling of the Dynamics of Salmonella Cerro Infection in a US Dairy Herd

    NASA Astrophysics Data System (ADS)

    Chapagain, Prem; van Kessel, Jo Ann; Karns, Jeffrey; Wolfgang, David; Schukken, Ynte; Grohn, Yrjo

    2006-03-01

    Salmonellosis has been one of the major causes of human foodborne illness in the US. The high prevalence of infections makes transmission dynamics of Salmonella in a farm environment of interest both from animal and human health perspectives. Mathematical modeling approaches are increasingly being applied to understand the dynamics of various infectious diseases in dairy herds. Here, we describe the transmission dynamics of Salmonella infection in a dairy herd with a set of non-linear differential equations. Although the infection dynamics of different serotypes of Salmonella in cattle are likely to be different, we find that a relatively simple SIR-type model can describe the observed dynamics of the Salmonella enterica serotype Cerro infection in the herd.

  18. A differential equation model of HIV infection of CD4+ T-cells with cure rate

    NASA Astrophysics Data System (ADS)

    Zhou, Xueyong; Song, Xinyu; Shi, Xiangyun

    2008-06-01

    A differential equation model of HIV infection of CD4+ T-cells with cure rate is studied. We prove that if the basic reproduction number R0<1, the HIV infection is cleared from the T-cell population and the disease dies out; if R0>1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if R0>1. Furthermore, we also obtain the conditions for which the system exists an orbitally asymptotically stable periodic solution. Numerical simulations are presented to illustrate the results.

  19. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells

    PubMed Central

    Drummond, Coyne G.

    2015-01-01

    ABSTRACT Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and

  20. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    PubMed

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  1. Efficacy of a Novel Tricyclic Topoisomerase Inhibitor in a Murine Model of Neisseria gonorrhoeae Infection.

    PubMed

    Savage, Victoria J; Charrier, Cédric; Salisbury, Anne-Marie; Box, Helen; Chaffer-Malam, Nathan; Huxley, Anthony; Kirk, Ralph; Noonan, Gary M; Mohmed, Sarfraz; Craighead, Mark W; Ratcliffe, Andrew J; Best, Stuart A; Stokes, Neil R

    2016-09-01

    There is an urgent need for new antibiotics to treat multidrug-resistant Neisseria gonorrhoeae In this report, the microbiology, in vivo pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced N. gonorrhoeae infection after a single dose in a mouse model of gonorrhea. These data support the potential of this series of small molecules as a new treatment for drug-resistant gonorrheal infections. PMID:27324777

  2. On cell resistance and immune response time lag in a model for the HIV infection

    NASA Astrophysics Data System (ADS)

    Solovey, Guillermo; Peruani, Fernando; Ponce Dawson, Silvina; Maria Zorzenon dos Santos, Rita

    2004-11-01

    Recently, a cellular automata model has been introduced (Phys. Rev. Lett. 87 (2001) 168102) to describe the spread of the HIV infection among target cells in lymphoid tissues. The model reproduces qualitatively the entire course of the infection displaying, in particular, the two time scales that characterize its dynamics. In this work, we investigate the robustness of the model against changes in three of its parameters. Two of them are related to the resistance of the cells to get infected. The other one describes the time interval necessary to mount specific immune responses. We have observed that an increase of the cell resistance, at any stage of the infection, leads to a reduction of the latency period, i.e., of the time interval between the primary infection and the onset of AIDS. However, during the early stages of the infection, when the cell resistance increase is combined with an increase in the initial concentration of infected cells, the original behavior is recovered. Therefore we find a long and a short latency regime (eight and one year long, respectively) depending on the value of the cell resistance. We have obtained, on the other hand, that changes on the parameter that describes the immune system time lag affects the time interval during which the primary infection occurs. Using different extended versions of the model, we also discuss how the two-time scale dynamics is affected when we include inhomogeneities on the cells properties, as for instance, on the cell resistance or on the time interval to mount specific immune responses.

  3. Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

    PubMed Central

    Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

    2015-01-01

    ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of

  4. The SCID-hu mouse as a model for HIV-1 infection.

    PubMed

    Aldrovandi, G M; Feuer, G; Gao, L; Jamieson, B; Kristeva, M; Chen, I S; Zack, J A

    1993-06-24

    During normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect. The model is constructed by implanting human fetal liver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.

  5. A structured avian influenza model with imperfect vaccination and vaccine-induced asymptomatic infection.

    PubMed

    Gulbudak, Hayriye; Martcheva, Maia

    2014-10-01

    We introduce a model of avian influenza in domestic birds with imperfect vaccination and age-since-vaccination structure. The model has four components: susceptible birds, vaccinated birds (stratified by vaccination age), asymptomatically infected birds, and infected birds. The model includes reduction in the probability of infection, decreasing severity of disease of vaccinated birds and vaccine waning. The basic reproduction number, [Formula: see text], is calculated. The disease-free equilibrium is found to be globally stable under certain conditions when [Formula: see text]. When [Formula: see text], existence of an endemic equilibrium is proved (with uniqueness for the ODE case and local stability under stricter conditions) and uniform persistence of the disease is established. The inclusion of reduction in susceptibility of vaccinated birds, reduction in infectiousness of asymptomatically infected birds and vaccine waning can have important implications for disease control. We analytically and numerically demonstrate that vaccination can paradoxically increase the total number of infected, resulting in the "silent spread" of the disease. We also study the effects of vaccine efficacy on disease prevalence and the minimum critical vaccination coverage, a threshold value for vaccination coverage to avoid an increase in total disease prevalence due to asymptomatic infection. PMID:25230802

  6. Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis.

    PubMed

    Charlier, Nathalie; Leyssen, Pieter; Paeshuyse, Jan; Drosten, Christian; Schmitz, Herbert; Van Lommel, Alfons; De Clercq, Erik; Neyts, Johan

    2002-08-01

    We have established a convenient animal model for flavivirus encephalitis using Montana Myotis leukoencephalitis virus (MMLV), a bat flavivirus. This virus has the same genomic organization, and contains the same conserved motifs in genes that encode potential antiviral targets, as flaviviruses that cause disease in man (N. Charlier et al., accompanying paper), and has a similar particle size (approximately 40 nm). MMLV replicates well in Vero cells and appears to be equally as sensitive as yellow fever virus and dengue fever virus to a selection of experimental antiviral agents. Cells infected with MMLV show dilation of the endoplasmic reticulum, a characteristic of flavivirus infection. Intraperitoneal, intranasal or direct intracerebral inoculation of SCID mice with MMLV resulted in encephalitis ultimately leading to death, whereas immunocompetent mice were refractory to either intranasal or intraperitoneal infection with MMLV. Viral RNA and/or antigens were detected in the brain and serum of MMLV-infected SCID mice, but not in any other organ examined: MMLV was detected in the olfactory lobes, the cerebral cortex, the limbic structures, the midbrain, cerebellum and medulla oblongata. Infection was confined to neurons. Treatment with the interferon-alpha/beta inducer poly(I).poly(C) protected SCID mice against MMLV-induced morbidity and mortality, and this protection correlated with a reduction in infectious virus titre and viral RNA load. This validates the MMLV model for use in antiviral drug studies. The MMLV SCID model may, therefore, be attractive for the study of chemoprophylactic or chemotherapeutic strategies against flavivirus infections causing encephalitis.

  7. Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations.

    PubMed

    Andréjak, Claire; Almeida, Deepak V; Tyagi, Sandeep; Converse, Paul J; Ammerman, Nicole C; Grosset, Jacques H

    2015-04-01

    The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. PMID:25624335

  8. [Stability Analysis of Susceptible-Infected-Recovered Epidemic Model].

    PubMed

    Pan, Duotao; Shi, Hongyan; Huang, Mingzhong; Yuan, Decheng

    2015-10-01

    With the range of application of computational biology and systems biology gradually expanding, the complexity of the bioprocess models is also increased. To address this difficult problem, it is required to introduce positive alternative analysis method to cope with it. Taking the dynamic model of the epidemic control process as research object, we established an evaluation model in our laboratory. Firstly, the model was solved with nonlinear programming method. The results were shown to be good. Based on biochemical systems theory, the ODE dynamic model was transformed into S-system. The eigen values of the model showed that the system was stable and contained oscillation phenomenon. Next the sensitivities of rate constant and logarithmic gains of the three key parameters were analyzed, as well as the robust of the system. The result indicated that the biochemical systems theory could be applied in different fields more widely. PMID:26964304

  9. The Utility of a Tissue Slice Model System to Determine Breast Cancer Infectivity by Oncolytic Adenoviruses

    PubMed Central

    Pennington, Krista; Chu, Quyen D.; Curiel, David T.; Li, Benjamin D.L.; Mathis, J. Michael

    2010-01-01

    Background Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and it has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time PCR to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results Infection and replication of our tropism modified oncolytic virus has been observed in breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing RFP expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 hours after infection in human breast tumor slices. Conclusions We have shown that a tropism modified oncolytic oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility. PMID:20691986

  10. Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models

    PubMed Central

    Bocharov, Gennady; Argilaguet, Jordi; Meyerhans, Andreas

    2015-01-01

    Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called “coordinatization” (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge. PMID:26576439

  11. Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models.

    PubMed

    Bocharov, Gennady; Argilaguet, Jordi; Meyerhans, Andreas

    2015-01-01

    Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge. PMID:26576439

  12. An Ex vivo culture model for placental cytomegalovirus infection using slices of Guinea pig placental tissue.

    PubMed

    Yamada, Souichi; Katano, Harutaka; Sato, Yuko; Fukuchi, Saki; Hashimoto, Kaede; Inoue, Naoki

    2016-01-01

    Congenital infection with human cytomegalovirus (CMV) through the placenta is one of the major causes of birth and developmental abnormalities. Guinea pig CMV (GPCMV) causes in utero infection, which makes its animal models useful for studies on congenital diseases. Here, we established an ex vivo culture method for tissue slices prepared from guinea pig placentas and demonstrated that viral spread in the model resembles those in the placenta of GPCMV-infected animals and that the infection is independent of the pentameric glycoprotein complex for endothelial/epithelial cell tropism. Thus, this model affords a useful tool for pathobiological studies on CMV placental infection.

  13. A Developmental Neuropsychological Model for the Study of Children with HIV Infection.

    ERIC Educational Resources Information Center

    Gioia, Gerard A.; And Others

    A developmental neuropsychological model is presented to address critical factors critical to the functional outcome in children with human immunodeficiency virus (HIV) infection. In the model, which is derived from work at the Boston Children's Hospital Acquired Immune Deficiency Syndrome (AIDS) program, neuropsychological outcomes are determined…

  14. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    PubMed Central

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  15. Simulating transmission and control of Taenia solium infections using a Reed-Frost stochastic model.

    PubMed

    Kyvsgaard, Niels C; Johansen, Maria Vang; Carabin, Hélène

    2007-04-01

    The transmission dynamics of the human-pig zoonotic cestode Taenia solium are explored with both deterministic and stochastic versions of a modified Reed-Frost model. This model, originally developed for microparasitic infections (i.e. bacteria, viruses and protozoa), assumes that random contacts occur between hosts and that hosts can be either susceptible, infected or 'recovered and presumed immune'. Transmission between humans and pigs is modelled as susceptible roaming pigs scavenging on human faeces infected with T. solium eggs. Transmission from pigs to humans is modelled as susceptible humans eating under-cooked pork meat harbouring T. solium metacestodes. Deterministic models of each scenario were first run, followed by stochastic versions of the models to assess the likelihood of infection elimination in the small population modelled. The effects of three groups of interventions were investigated using the model: (i) interventions affecting the transmission parameters such as use of latrines, meat inspection, and cooking habits; (ii) routine interventions including rapid detection and treatment of human carriers or pig vaccination; and (iii) treatment interventions of either humans or pigs. It is concluded that mass-treatment can result in a short term dramatic reduction in prevalence, whereas interventions targeting interruption of the life cycle lead to long-term reduction in prevalence.

  16. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  17. ModeLang: a new approach for experts-friendly viral infections modeling.

    PubMed

    Wasik, Szymon; Prejzendanc, Tomasz; Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses.

  18. A time-periodic reaction-diffusion epidemic model with infection period

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Wang, Zhi-Cheng

    2016-10-01

    In this paper, we propose a time-periodic and diffusive SIR epidemic model with constant infection period. By introducing the basic reproduction number R_0 via a next generation operator for this model, we show that the disease goes extinction if R_0 < 1; while the disease is uniformly persistent if R_0 > 1.

  19. Modulated Fluorophore Signal Recovery Buried within Tissue Mimicking Phantoms

    PubMed Central

    Sarkar, Saugata; Fan, Chaoyang; Hsiang, Jung-Cheng; Dickson, Robert M.

    2013-01-01

    Optically modulated fluorescence from ~140nM Cy5 is visualized when embedded up to 6 mm within skin tissue-mimicking phantoms, even in the presence of overwhelming background fluorescence and scatter. Experimental and finite element analysis (FEA)-based computational models yield excellent agreement in signal levels and predict biocompatible temperature changes. Using Synchronously Amplified Fluorescence Image Recovery (SAFIRe), dual laser excitation (primary laser: λ = 594nm, 0.29 kW/cm2; secondary laser: λ = 710nm, 5.9 kW/cm2, intensity-modulated at 100Hz) simultaneously excites fluorescence, and dynamically optically reverses the dark state buildup of primary laser-excited Cy5 molecules. As the modulated secondary laser both directly modulates Cy5 emission and is of lower energy than the collected Cy5 fluorescence, modulated Cy5 fluorescence in phantoms is free of obscuring background emission. The modulated fluorescence emission due to the secondary laser was recovered by Fourier transformation, yielding a specific and unique signature of the introduced fluorophores, with largely background-free detection, at excitation intensities close to the maximum permissible exposure (MPE) for skin. Experimental and computational models agree to within 8%, validating the computational model. As modulated fluorescence depends on the presence of both lasers, depth information as a function of focal position is also readily obtained from recovered modulated signal strength. PMID:23692258

  20. Synchrony and motor mimicking in chimpanzee observational learning.

    PubMed

    Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

    2014-06-13

    Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function.

  1. Microfabricated adhesive mimicking gecko foot-hair

    NASA Astrophysics Data System (ADS)

    Geim, A. K.; Dubonos, S. V.; Grigorieva, I. V.; Novoselov, K. S.; Zhukov, A. A.; Shapoval, S. Yu.

    2003-07-01

    The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force ~10-7 N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of ~10 N cm-2: sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.

  2. Microfabricated adhesive mimicking gecko foot-hair.

    PubMed

    Geim, A K; Dubonos, S V; Grigorieva, I V; Novoselov, K S; Zhukov, A A; Shapoval, S Yu

    2003-07-01

    The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force approximately 10(-7) N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of approximately 10 N x cm(-2): sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.

  3. Microfabricated adhesive mimicking gecko foot-hair.

    PubMed

    Geim, A K; Dubonos, S V; Grigorieva, I V; Novoselov, K S; Zhukov, A A; Shapoval, S Yu

    2003-07-01

    The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force approximately 10(-7) N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of approximately 10 N x cm(-2): sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved. PMID:12776092

  4. SUMO-mimicking peptides inhibiting protein SUMOylation.

    PubMed

    Zhao, Bo; Villhauer, Eric B; Bhuripanyo, Karan; Kiyokawa, Hiroaki; Schindelin, Hermann; Yin, Jun

    2014-12-15

    The ubiquitin-like protein SUMO is transferred through a core E1-E2 cascade composed of the SUMO-activating enzyme (SAE) and Ubc9 to modify cellular proteins and transmit important biological signals. SAE primarily recognizes the C-terminal tail of SUMO and catalyzes ATP condensation with the SUMO C-terminal carboxylate to activate its transfer through the cascade. Here, we used phage display to show that a broad profile of SUMO C-terminal sequences could be activated by SAE. Based on this, we developed heptamer peptides that could 1) form thioester conjugates with SAE, 2) be transferred from SAE to Ubc9, and 3) be further transferred to the SUMOylation target protein RanGAP1. As these peptides recapitulate the action of SUMO in protein modification, we refer to them as "SUMO-mimicking peptides". We found that, once the peptides were conjugated to SAE and Ubc9, they blocked full-length SUMO from entering the cascade. These peptides can thus function as mechanism-based inhibitors of the protein SUMOylation reaction.

  5. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  6. Overview of Vertebrate Animal Models of Fungal Infection

    PubMed Central

    Hohl, Tobias M.

    2014-01-01

    Fungi represent emerging infectious threats to human populations worldwide. Mice and other laboratory animals have proved invaluable in modeling clinical syndromes associated with superficial and life-threatening invasive mycoses. This review outlines salient features of common vertebrate animal model systems to study fungal pathogenesis, host antifungal immune responses, and antifungal compounds. PMID:24709390

  7. Sequential Plasmodium chabaudi and Plasmodium berghei infections provide a novel model of severe malarial anemia.

    PubMed

    Harris, Juliana V; Bohr, Tiffany M; Stracener, Catherine; Landmesser, Mary E; Torres, Vladimir; Mbugua, Amos; Moratz, Chantal; Stoute, José A

    2012-09-01

    Lack of an adequate animal model of Plasmodium falciparum severe malarial anemia (SMA) has hampered the understanding of this highly lethal condition. We developed a model of SMA by infecting C57BL/6 mice with P. chabaudi followed after recovery by P. berghei infection. P. chabaudi/P. berghei-infected mice had an initial 9- to 10-day phase of relatively low parasitemia and severe anemia, followed by a second phase of hyperparasitemia, more profound anemia, reticulocytosis, and death 14 to 21 days after infection. P. chabaudi/P. berghei-infected animals had more intense splenic hematopoiesis, higher interleukin-10 (IL-10)/tumor necrosis factor alpha and IL-12/gamma interferon (IFN-γ) ratios, and higher antibody levels against P. berghei and P. chabaudi antigens than P. berghei-infected or P. chabaudi-recovered animals. Early treatment with chloroquine or artesunate did not prevent the anemia, suggesting that the bulk of red cell destruction was not due to the parasite. Red cells from P. chabaudi/P. berghei-infected animals had increased surface IgG and C3 by flow cytometry. However, C3(-/-) mice still developed anemia. Tracking of red cells labeled ex vivo and in vivo and analysis of frozen tissue sections by immunofluorescence microscopy showed that red cells from P. chabaudi/P. berghei-infected animals were removed at an accelerated rate in the liver by erythrophagocytosis. This model is practical and reproducible, and its similarities with P. falciparum SMA in humans makes it an appealing system with which to study the pathogenesis of this condition and explore potential immunomodulatory interventions.

  8. Non-harmful insertion of data mimicking computer network attacks

    DOEpatents

    Neil, Joshua Charles; Kent, Alexander; Hash, Jr, Curtis Lee

    2016-06-21

    Non-harmful data mimicking computer network attacks may be inserted in a computer network. Anomalous real network connections may be generated between a plurality of computing systems in the network. Data mimicking an attack may also be generated. The generated data may be transmitted between the plurality of computing systems using the real network connections and measured to determine whether an attack is detected.

  9. A Model of DENV-3 Infection That Recapitulates Severe Disease and Highlights the Importance of IFN-γ in Host Resistance to Infection

    PubMed Central

    Valadão, Deborah F.; Cisalpino, Daniel; Dias, Ana Carolina F.; Silveira, Kátia D.; Kangussu, Lucas M.; Ávila, Thiago V.; Bonfim, Maria Rosa Q.; Bonaventura, Daniela; Silva, Tarcília A.; Sousa, Lirlândia P.; Rachid, Milene A.; Vieira, Leda Q.; Menezes, Gustavo B.; de Paula, Ana Maria; Atrasheuskaya, Alena; Ignatyev, George; Teixeira, Mauro M.; Souza, Danielle G.

    2012-01-01

    There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ−/− mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2−/− mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection. PMID:22666512

  10. Pathogenesis of endometritis and salpingitis in a guinea pig model of chlamydial genital infection.

    PubMed Central

    Rank, R. G.; Sanders, M. M.

    1992-01-01

    The development of tubal obstruction and subsequent infertility is a major sequelum of upper genital tract infection with Chlamydia trachomatis; however, little is known about the pathogenesis of the infection. In this investigation, the authors present a detailed study of the progression of ascending chlamydial infection in female guinea pigs resulting from intravaginal inoculation of the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC). Isolation of chlamydiae from different tissues of the genital tract revealed definitive evidence for ascending infection that was not dose-related. By 7 days after infection, GPIC was isolated from the endometrium and oviducts of 78% of the animals. Pathologic changes analogous to those seen in human chlamydial disease, including polymorphonuclear, mononuclear, and plasma cell infiltration, were seen in the endometrium and oviducts, although not all isolation positive animals developed overt tubal disease. Long-term fibrosis, often in combination with hydrosalpinx, was noted in the mesosalpingeal tissue in 20% of the animals. Thus, the guinea pig:GPIC system represents a model for ascending chlamydial infection resulting from vaginal inoculation of normal guinea pigs that closely approximates the disease as seen in humans and can be used to study the pathogenesis of chlamydial genital infection. Images Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1562052

  11. Adipose Tissue Serves as a Reservoir for Recrudescent Rickettsia prowazekii Infection in a Mouse Model

    PubMed Central

    Bechah, Yassina; Paddock, Christopher D.; Capo, Christian; Mege, Jean-Louis; Raoult, Didier

    2010-01-01

    Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of β-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii. PMID:20049326

  12. Pathogenesis of endometritis and salpingitis in a guinea pig model of chlamydial genital infection.

    PubMed

    Rank, R G; Sanders, M M

    1992-04-01

    The development of tubal obstruction and subsequent infertility is a major sequelum of upper genital tract infection with Chlamydia trachomatis; however, little is known about the pathogenesis of the infection. In this investigation, the authors present a detailed study of the progression of ascending chlamydial infection in female guinea pigs resulting from intravaginal inoculation of the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC). Isolation of chlamydiae from different tissues of the genital tract revealed definitive evidence for ascending infection that was not dose-related. By 7 days after infection, GPIC was isolated from the endometrium and oviducts of 78% of the animals. Pathologic changes analogous to those seen in human chlamydial disease, including polymorphonuclear, mononuclear, and plasma cell infiltration, were seen in the endometrium and oviducts, although not all isolation positive animals developed overt tubal disease. Long-term fibrosis, often in combination with hydrosalpinx, was noted in the mesosalpingeal tissue in 20% of the animals. Thus, the guinea pig:GPIC system represents a model for ascending chlamydial infection resulting from vaginal inoculation of normal guinea pigs that closely approximates the disease as seen in humans and can be used to study the pathogenesis of chlamydial genital infection.

  13. Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

    PubMed Central

    Grguric-Smith, Laryssa M.; Lee, Hiu H.; Gandhi, Jay A.; Brennan, Melissa B.; DeLeon-Rodriguez, Carlos M.; Coelho, Carolina; Han, George; Martinez, Luis R.

    2015-01-01

    The Gram negative coccobacillus Acinetobacter baumannii has become an increasingly prevalent cause of hospital-acquired infections in recent years. The majority of clinical A. baumannii isolates display high-level resistance to antimicrobials, which severely compromises our capacity to care for patients with A. baumannii disease. Neutrophils are of major importance in the host defense against microbial infections. However, the contribution of these cells of innate immunity in host resistance to cutaneous A. baumannii infection has not been directly investigated. Hence, we hypothesized that depletion of neutrophils increases severity of bacterial disease in an experimental A. baumannii murine wound model. In this study, the Ly-6G-specific monoclonal antibody (mAb), 1A8, was used to generate neutropenic mice and the pathogenesis of several A. baumannii clinical isolates on wounded cutaneous tissue was investigated. We demonstrated that neutrophil depletion enhances bacterial burden using colony forming unit determinations. Also, mAb 1A8 reduces global measurements of wound healing in A. baumannii-infected animals. Interestingly, histological analysis of cutaneous tissue excised from A. baumannii-infected animals treated with mAb 1A8 displays enhanced collagen deposition. Furthermore, neutropenia and A. baumannii infection alter pro-inflammatory cytokine release leading to severe microbial disease. Our findings provide a better understanding of the impact of these innate immune cells in controlling A. baumannii skin infections. PMID:26528277

  14. Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model.

    PubMed

    Bechah, Yassina; Paddock, Christopher D; Capo, Christian; Mege, Jean-Louis; Raoult, Didier

    2010-01-01

    Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of beta-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii.

  15. In vivo modeling of biofilm-infected wounds: a review.

    PubMed

    Seth, Akhil K; Geringer, Matthew R; Hong, Seok J; Leung, Kai P; Mustoe, Thomas A; Galiano, Robert D

    2012-11-01

    Chronic wounds continue to represent a difficult and complex problem for both patients and healthcare providers. Bacterial biofilms represent a critical component of nonhealing wounds, utilizing several different mechanisms to inhibit innate inflammatory pathways and resist traditional therapeutics. Although in vitro biofilm systems have been well described and studied, understanding the intricacies of wound biofilm pathology requires appropriate in vivo models to understand the interactions between bacteria and host. In an effort to clarify the available literature, this review describes and critically evaluates all of the in vivo wound biofilm models currently published to-date, including model advantages and clinical applicability. We will also address the need for continued therapeutic development and testing using these currently available in vivo models.

  16. [Advances in the research of an animal model of wound due to Mycobacterium tuberculosis infection].

    PubMed

    Chen, Ling; Jia, Chiyu

    2015-12-01

    Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal.

  17. The effect of infected external computers on the spread of viruses: A compartment modeling study

    NASA Astrophysics Data System (ADS)

    Yang, Lu-Xing; Yang, Xiaofan

    2013-12-01

    Inevitably, there exist infected computers outside of the Internet. This paper aims to understand how infected external computers affect the spread of computer viruses. For that purpose, a new virus-antivirus spreading model, which takes into account the effect of infected/immune external computers, is established. A systematic study shows that, unlike most previous models, the proposed model admits no virus-free equilibrium and admits a globally asymptotically stable viral equilibrium. This result implies that it would be practically impossible to eradicate viruses on the Internet. As a result, inhibiting the virus prevalence to below an acceptable level would be the next best thing. A theoretical study reveals the effect of different parameters on the steady virus prevalence. On this basis, a number of suggestions are made so as to contain virus spreading.

  18. A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Zhang Lichun; Weng Shaoping; Huang Zhijian; Lu Jing; Lan Dongming; Zhong Xuejun; Yu Xiaoqiang; Xu Anlong He Jianguo

    2008-06-20

    Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV was replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.

  19. A rhesus macaque model of Asian-lineage Zika virus infection

    PubMed Central

    Dudley, Dawn M.; Aliota, Matthew T.; Mohr, Emma L.; Weiler, Andrea M.; Lehrer-Brey, Gabrielle; Weisgrau, Kim L.; Mohns, Mariel S.; Breitbach, Meghan E.; Rasheed, Mustafa N.; Newman, Christina M.; Gellerup, Dane D.; Moncla, Louise H.; Post, Jennifer; Schultz-Darken, Nancy; Schotzko, Michele L.; Hayes, Jennifer M.; Eudailey, Josh A.; Moody, M. Anthony; Permar, Sallie R.; O'Connor, Shelby L.; Rakasz, Eva G.; Simmons, Heather A.; Capuano, Saverio; Golos, Thaddeus G.; Osorio, Jorge E.; Friedrich, Thomas C.; O'Connor, David H.

    2016-01-01

    Infection with Asian-lineage Zika virus (ZIKV) has been associated with Guillain–Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage ZIKV closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, ZIKV RNA is detected in plasma 1 day post infection (d.p.i.) in all animals (N=8, including 2 pregnant animals), and is also present in saliva, urine and cerebrospinal fluid. Non-pregnant and pregnant animals remain viremic for 21 days and for up to at least 57 days, respectively. Neutralizing antibodies are detected by 21 d.p.i. Rechallenge 10 weeks after the initial challenge results in no detectable virus replication, indicating protective immunity against homologous strains. Therefore, Asian-lineage ZIKV infection of rhesus macaques provides a relevant animal model for studying pathogenesis and evaluating potential interventions against human infection, including during pregnancy. PMID:27352279

  20. A rhesus macaque model of Asian-lineage Zika virus infection.

    PubMed

    Dudley, Dawn M; Aliota, Matthew T; Mohr, Emma L; Weiler, Andrea M; Lehrer-Brey, Gabrielle; Weisgrau, Kim L; Mohns, Mariel S; Breitbach, Meghan E; Rasheed, Mustafa N; Newman, Christina M; Gellerup, Dane D; Moncla, Louise H; Post, Jennifer; Schultz-Darken, Nancy; Schotzko, Michele L; Hayes, Jennifer M; Eudailey, Josh A; Moody, M Anthony; Permar, Sallie R; O'Connor, Shelby L; Rakasz, Eva G; Simmons, Heather A; Capuano, Saverio; Golos, Thaddeus G; Osorio, Jorge E; Friedrich, Thomas C; O'Connor, David H

    2016-06-28

    Infection with Asian-lineage Zika virus (ZIKV) has been associated with Guillain-Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage ZIKV closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, ZIKV RNA is detected in plasma 1 day post infection (d.p.i.) in all animals (N=8, including 2 pregnant animals), and is also present in saliva, urine and cerebrospinal fluid. Non-pregnant and pregnant animals remain viremic for 21 days and for up to at least 57 days, respectively. Neutralizing antibodies are detected by 21 d.p.i. Rechallenge 10 weeks after the initial challenge results in no detectable virus replication, indicating protective immunity against homologous strains. Therefore, Asian-lineage ZIKV infection of rhesus macaques provides a relevant animal model for studying pathogenesis and evaluating potential interventions against human infection, including during pregnancy.

  1. A rhesus macaque model of Asian-lineage Zika virus infection.

    PubMed

    Dudley, Dawn M; Aliota, Matthew T; Mohr, Emma L; Weiler, Andrea M; Lehrer-Brey, Gabrielle; Weisgrau, Kim L; Mohns, Mariel S; Breitbach, Meghan E; Rasheed, Mustafa N; Newman, Christina M; Gellerup, Dane D; Moncla, Louise H; Post, Jennifer; Schultz-Darken, Nancy; Schotzko, Michele L; Hayes, Jennifer M; Eudailey, Josh A; Moody, M Anthony; Permar, Sallie R; O'Connor, Shelby L; Rakasz, Eva G; Simmons, Heather A; Capuano, Saverio; Golos, Thaddeus G; Osorio, Jorge E; Friedrich, Thomas C; O'Connor, David H

    2016-01-01

    Infection with Asian-lineage Zika virus (ZIKV) has been associated with Guillain-Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage ZIKV closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, ZIKV RNA is detected in plasma 1 day post infection (d.p.i.) in all animals (N=8, including 2 pregnant animals), and is also present in saliva, urine and cerebrospinal fluid. Non-pregnant and pregnant animals remain viremic for 21 days and for up to at least 57 days, respectively. Neutralizing antibodies are detected by 21 d.p.i. Rechallenge 10 weeks after the initial challenge results in no detectable virus replication, indicating protective immunity against homologous strains. Therefore, Asian-lineage ZIKV infection of rhesus macaques provides a relevant animal model for studying pathogenesis and evaluating potential interventions against human infection, including during pregnancy. PMID:27352279

  2. Establishment of Infection Models in Zebrafish Larvae (Danio rerio) to Study the Pathogenesis of Aeromonas hydrophila.

    PubMed

    Saraceni, Paolo R; Romero, Alejandro; Figueras, Antonio; Novoa, Beatriz

    2016-01-01

    Aeromonas hydrophila is a Gram-negative opportunistic pathogen of fish and terrestrial animals. In humans, A. hydrophila mainly causes gastroenteritis, septicaemia, and tissue infections. The mechanisms of infection, the main virulence factors and the host immune response triggered by A. hydrophila have been studied in detail using murine models and adult fish. However, the great limitation of studying adult animals is that the animal must be sacrificed and its tissues/organs extracted, which prevents the study of the infectious processes in the whole living animal. Zebrafish larvae are being used for the analysis of several infectious diseases, but their use for studying the pathogenesis of A. hydrophila has never been explored. The great advantage of zebrafish larvae is their transparency during the first week after fertilization, which allows detailed descriptions of the infectious processes using in vivo imaging techniques such as differential interferential contrast (DIC) and fluorescence microscopy. Moreover, the availability of fluorescent pathogens and transgenic reporter zebrafish lines expressing fluorescent immune cells, immune marker genes or cytokines/chemokines allows the host-pathogen interactions to be characterized. The present study explores the suitability of zebrafish larvae to study the pathogenesis of A. hydrophila and the interaction mechanisms between the bacterium and the innate immune responses through an infection model using different routes for infection. We used an early-embryo infection model at 3 days post-fertilization (dpf) through the microinjection of A. hydrophila into the duct of Cuvier, caudal vein, notochord, or muscle and two bath infection models using 4 dpf healthy and injured larvae. The latter resembled the natural conditions under which A. hydrophila produces infectious diseases in animals. We compared the cellular processes after infection in each anatomical site by confocal fluorescence imaging and determined the

  3. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection

    PubMed Central

    Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R.; Valbuena, Gustavo; Walker, David H.; Bouyer, Donald H.

    2016-01-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11–12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14–19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

  4. Establishment of Infection Models in Zebrafish Larvae (Danio rerio) to Study the Pathogenesis of Aeromonas hydrophila

    PubMed Central

    Saraceni, Paolo R.; Romero, Alejandro; Figueras, Antonio; Novoa, Beatriz

    2016-01-01

    Aeromonas hydrophila is a Gram-negative opportunistic pathogen of fish and terrestrial animals. In humans, A. hydrophila mainly causes gastroenteritis, septicaemia, and tissue infections. The mechanisms of infection, the main virulence factors and the host immune response triggered by A. hydrophila have been studied in detail using murine models and adult fish. However, the great limitation of studying adult animals is that the animal must be sacrificed and its tissues/organs extracted, which prevents the study of the infectious processes in the whole living animal. Zebrafish larvae are being used for the analysis of several infectious diseases, but their use for studying the pathogenesis of A. hydrophila has never been explored. The great advantage of zebrafish larvae is their transparency during the first week after fertilization, which allows detailed descriptions of the infectious processes using in vivo imaging techniques such as differential interferential contrast (DIC) and fluorescence microscopy. Moreover, the availability of fluorescent pathogens and transgenic reporter zebrafish lines expressing fluorescent immune cells, immune marker genes or cytokines/chemokines allows the host–pathogen interactions to be characterized. The present study explores the suitability of zebrafish larvae to study the pathogenesis of A. hydrophila and the interaction mechanisms between the bacterium and the innate immune responses through an infection model using different routes for infection. We used an early-embryo infection model at 3 days post-fertilization (dpf) through the microinjection of A. hydrophila into the duct of Cuvier, caudal vein, notochord, or muscle and two bath infection models using 4 dpf healthy and injured larvae. The latter resembled the natural conditions under which A. hydrophila produces infectious diseases in animals. We compared the cellular processes after infection in each anatomical site by confocal fluorescence imaging and determined the

  5. An experimental intratonsilar infection model for bovine tuberculosis in African buffaloes, Syncerus caffer.

    PubMed

    De Klerk, L; Michel, A L; Grobler, D G; Bengis, R G; Bush, M; Kriek, N P J; Hofmeyr, M S; Griffin, J F T; Mackintosh, C G

    2006-12-01

    An infection model for Mycobacterium bovis in African buffaloes, Syncerus caffer, was developed, using the intratonsilar route of inoculation. Two groups of 11 buffaloes each, aged approximately 18 months, were infected with either 3.2 x 10(2) cfu (low dose) or 3 x 10(4) cfu (high dose) of M. bovis strain isolated from a buffalo. A control group of six buffaloes received saline via the same route. The infection status was monitored in vivo using the comparative intradermal tuberculin test, and in vitro by the modified interferon-gamma assay. All buffaloes were euthanazed 22 weeks post infection and lesion development was assessed by macroscopic examination, culture and histopathology. It was found that the high dose caused macroscopic lesions in nine out of 11 buffaloes. Mycobacterium bovis was isolated from all buffaloes in the high-dose group and from six out of 11 in the low-dose group.

  6. The cotton rat (Sigmodon hispidus) as an animal model for respiratory tract infections with human pathogens.

    PubMed

    Green, M Gia; Huey, Devra; Niewiesk, Stefan

    2013-05-01

    Respiratory viral infection is a great human health concern, resulting in disease, death and economic losses. Cotton rats (Sigmodon hispidus) have been particularly useful in the study of the pathogenesis of human respiratory virus infections, including the development and testing of antiviral compounds and vaccines. In this article, the authors outline the advantages of the cotton rat compared with the mouse as a model for infection with measles virus, respiratory syncytial virus, influenza virus, human parainfluenza virus and human metapneumovirus. From the literature and their own experience, the authors summarize guidelines for handling, maintaining and breeding cotton rats. In addition, they offer technical tips for carrying out infection experiments and provide information about the large array of immunological assays and reagents available for the study of immune responses (macrophages, dendritic cells, T cells, B cells, antibodies, chemokines and cytokines) in cotton rats.

  7. Persistence of intestinal antibody response to heterologous rotavirus infection in a murine model beyond 1 year.

    PubMed Central

    Shaw, R D; Merchant, A A; Groene, W S; Cheng, E H

    1993-01-01

    We used an ELISPOT (enzyme-linked immunosorbent spot) assay to quantitate the long-term rotavirus-specific intestinal antibody response in a murine model. The frequency of murine intestinal antibody-secreting cells (ASCs) was followed for a period of 1 year after a single dose of rhesus rotavirus (10(6) PFU) was administered at 10 days of age. Some animals were boosted at that time with a second dose. One year after infection, virus-specific ASCs declined from acute-phase levels, but they were still present at significant levels (1.32 x 10(4) virus-specific ASCs per 10(6) intestinal mononuclear cells; approximately 17% of the previously reported response at 1 month after infection). A booster dose 1 year after the primary infection produced a 100% increase in virus-specific ASCs but did not restore the response to that of the primary infection. PMID:8381806

  8. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice

    PubMed Central

    Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

    2016-01-01

    Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future. PMID:27196107

  9. Fate of pathogenic bacteria in microcosms mimicking human body sites.

    PubMed

    Castellani, Francesco; Ghidini, Valentina; Tafi, Maria Carla; Boaretti, Marzia; Lleo, Maria M

    2013-07-01

    During the infectious process, pathogens may reach anatomical sites where they are exposed to substances interfering with their growth. These substances can include molecules produced by the host, and his resident microbial population, as well as exogenous antibacterial drugs. Suboptimal concentrations of inhibitory molecules and stress conditions found in vivo (high or low temperatures, lack of oxygen, extreme pH) might induce in bacteria the activation of survival mechanisms blocking their division capability but allowing them to stay alive. These "dormant" bacteria can be reactivated in particular circumstances and would be able to express their virulence traits. In this study, it was evaluated the effect of some environmental conditions, such as optimal and suboptimal temperatures, direct light and antibiotic sub-inhibitory concentrations doses of antibiotic, on the human pathogens Escherichia coli and Enterococcus faecalis when incubated in fluids accumulated in the body of patients with different pathologies. It is shown that inoculation in a number of accumulated body fluids and the presence of gentamicin, reliable conditions encountered during pathological states, induce stress-responding strategies enabling bacteria to persist in microcosms mimicking the human body. Significant differences were detected in Gram-negative and Gram-positive species with E. faecalis surviving, as starved or viable but non-culturable forms, in any microcosm and condition tested and E. coli activating a viable but non-culturable state only in some clinical samples. The persistence of bacteria under these conditions, being non-culturable, might explain some recurrent infections without isolation of the causative agent after application of the standard microbiological methods.

  10. Chlamydial infection increases gonococcal colonization in a novel murine coinfection model.

    PubMed

    Vonck, Rachel A; Darville, T; O'Connell, C M; Jerse, Ann E

    2011-04-01

    Genital tract infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis serovars D to K occur at high incidence in many areas of the world. Despite high rates of coinfection with these pathogens, investigations of host-parasite interactions have focused on each pathogen individually. We describe here a coinfection model in which female BALB/c mice were first infected with the mouse Chlamydia species C. muridarum and then inoculated with N. gonorrhoeae following treatment with water-soluble 17β-estradiol to promote long-term gonococcal infection. Viable gonococci and chlamydiae were recovered for an average of 8 to 10 days, and diplococci and chlamydial inclusions were observed in lower genital tract tissue by immunohistochemical staining. Estradiol treatment reduced proinflammatory cytokine and chemokine levels in chlamydia-infected mice; however, coinfected mice had a higher percentage of vaginal neutrophils compared to mice infected with either pathogen alone. We detected no difference in pathogen-specific antibody levels due to coinfection. Interestingly, significantly more gonococci were recovered from coinfected mice compared to mice infected with N. gonorrhoeae alone. We found no evidence that C. muridarum increases gonococcal adherence to, or invasion of, immortalized murine epithelial cells. However, increased vaginal concentrations of inflammatory mediators macrophage inflammatory protein 2 and tumor necrosis factor alpha were detected in C. muridarum-infected mice prior to inoculation with N. gonorrhoeae concurrently with the downregulation of cathelicidin-related antimicrobial peptide and secretory leukocyte peptidase inhibitor genes. We conclude that female mice can be successfully infected with both C. muridarum and N. gonorrhoeae and that chlamydia-induced alterations in host innate responses may enhance gonococcal infection. PMID:21245268

  11. A susceptible-infected model of early detection of respiratory infection outbreaks on a background of influenza.

    PubMed

    Mohtashemi, Mojdeh; Szolovits, Peter; Dunyak, James; Mandl, Kenneth D

    2006-08-21

    The threat of biological warfare and the emergence of new infectious agents spreading at a global scale have highlighted the need for major enhancements to the public health infrastructure. Early detection of epidemics of infectious diseases requires both real-time data and real-time interpretation of data. Despite moderate advancements in data acquisition, the state of the practice for real-time analysis of data remains inadequate. We present a nonlinear mathematical framework for modeling the transient dynamics of influenza, applied to historical data sets of patients with influenza-like illness. We estimate the vital time-varying epidemiological parameters of infections from historical data, representing normal epidemiological trends. We then introduce simulated outbreaks of different shapes and magnitudes into the historical data, and estimate the parameters representing the infection rates of anomalous deviations from normal trends. Finally, a dynamic threshold-based detection algorithm is devised to assess the timeliness and sensitivity of detecting the irregularities in the data, under a fixed low false-positive rate. We find that the detection algorithm can identify such designated abnormalities in the data with high sensitivity with specificity held at 97%, but more importantly, early during an outbreak. The proposed methodology can be applied to a broad range of influenza-like infectious diseases, whether naturally occurring or a result of bioterrorism, and thus can be an integral component of a real-time surveillance system. PMID:16556450

  12. Drosophila melanogaster as an Animal Model for the Study of Pseudomonas aeruginosa Biofilm Infections In Vivo

    PubMed Central

    Mulcahy, Heidi; Sibley, Christopher D.; Surette, Michael G.; Lewenza, Shawn

    2011-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3) demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo. PMID:21998591

  13. Latent porcine circovirus type 2-infected domestic pigs: A potential infection model for the effective development of vaccines against latent or chronic virus induced diseases.

    PubMed

    Sydler, Titus; Brägger, Stefanie; Handke, Martin; Hartnack, Sonja; Lewis, Fraser I; Sidler, Xaver; Brugnera, Enrico

    2016-02-17

    Until recently, knowledge of the pathogenicity of Circoviridae and Anelloviridae family members was limited. Our previous discoveries provided clues toward resolving this issue based on studies of the latent nature of porcine circovirus type 2 (PCV2) genotype group members. We developed a conventional pig infection model that indicated that weaners already harbored latent PCV2 infection in the thymus, which enabled the viruses to specifically modulate the maturation of T-helper cells. This finding raised the possibility that the thymi of normal fetuses were already infected with PCV2. The present findings further substantiate our hypothesis that PCV2 masquerades as the host by infecting fetuses before they acquire immune-competence. We provide the first demonstration that all domestic pig fetuses preferentially harbor latent PCV2-infected cells in their thymi. These PCV2-infected cells are different from thymocytes and are located in the medulla of the fetal thymus. These latent PCV2-infected cells in fetuses are found at the same location and share characteristics with the infected cells observed in adolescent pigs. Moreover, fetuses also harbor these infected cells in other lymph system organs. We provide the first demonstration that the fetal thymus virus pools are minimally affected by sow vaccination, highlighting the immune-privileged character of this organ. Furthermore, we found a striking reduction in virus-infected cells in the fetal spleen and an increase in PCV2-infected cells in the fetal intestine of anti-PCV2-vaccinated mothers. These data indicate that specific immune response interactions occur between mothers and their progeny that are not dependent on the humoral immunity of the mother and cannot be attributed to the rudimentary humoral responses of the fetuses because these pig fetuses do not have any PCV2-specific antibodies. These shifts in our understanding of the PCV2-infected cell pool will lead to different avenues in the search for

  14. [Perinephric liposarcoma mimicking cystic renal tumor].

    PubMed

    Horiguchi, Akio; Oyama, Masafumi

    2002-03-01

    Liposarcoma is one of the most common primary retroperitoneal neoplasms, and the perinephric region is a frequent location for them. Liposarcomas show a variety of radiographic features in terms of histological types and tumor sizes, so the specific diagnosis of liposarcoma is often difficult. We present a unique case of perinephric dedifferentiated liposarcoma mimicking cystic renal tumor. A 71-year-old man presented himself at our hospital with a palpable mass in his upper right abdomen. Abdominal computerized tomography (CT) revealed a well-defined cystic mass at the lower pole of the right kidney that contained heterogeneous solid components and small foci of fat. There were no signs of lymphadenopathy or tumor thrombus in the renal vein. Metastatic evaluation by chest x-ray and bone scan was negative. The probable diagnosis was cystic renal cell carcinoma or atypical angiomyolipoma. Because we could not exclude the possibility of cystic malignancy, a right radical nephrectomy was performed. Grossly, the tumor was predominantly encapsulated by a unilocular fibrous capsule and was filled with bloody fluid and debris. The anterior portion of the tumor was composed of various-sized soft and rubbery masses covered with necrotic tissue. The histological diagnosis was dedifferentiated liposarcoma arising in the perinephric retroperitoneum with extensive necrosis, and the cyst wall was composed of a necrotic tumor with a well differentiated liposarcoma and a fibrous capsule. Although the tumor widely covered the right kidney, there was no microscopic invasion of the kidney. No signs of tumor recurrence were noted six months after the operation.

  15. Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports

    NASA Astrophysics Data System (ADS)

    Jiao, Jianjun; Cai, Shaohong; Li, Limei

    2016-05-01

    To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.

  16. A two-compartment model of osmotic lysis in Plasmodium falciparum-infected erythrocytes.

    PubMed

    Wagner, Marissa A; Andemariam, Biree; Desai, Sanjay A

    2003-01-01

    We recently identified a voltage-dependent anion channel on the surface of human red blood cells (RBCs) infected with the malaria parasite, Plasmodium falciparum. This channel, the plasmodial erythrocyte surface anion channel (PESAC), likely accounts for the increased permeability of infected RBCs to various small solutes, as assessed quantitatively with radioisotope flux and patch-clamp studies. Whereas this increased permeability has also been studied by following osmotic lysis of infected cells in permeant solutes, these experiments have been limited to qualitative comparisons of lysis rates. To permit more quantitative examination of lysis rates, we have developed a mathematical model for osmotic fragility of infected cells based on diffusional uptake via PESAC and the two-compartment geometry of infected RBCs. This model, combined with a simple light scattering assay designed to track osmotic lysis precisely, produced permeability coefficients that match both previous isotope flux and patch-clamp estimates. Our model and light scattering assay also revealed Michaelian kinetics for inhibition of PESAC by furosemide, suggesting a 1:1 stoichiometry for their interaction. PMID:12524269

  17. Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions

    PubMed Central

    Aldabe, Rafael; Suárez-Amarán, Lester; Usai, Carla; González-Aseguinolaza, Gloria

    2015-01-01

    Hepatitis delta virus (HDV) is a defective RNA virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis B virus (HBV) for its replication and formation of new virions. HDV infection is usually associated with a worsening of HBV-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (HCC), and fulminant hepatitis. Importantly, no selective therapies are available for HDV infection. The mainstay of treatment for HDV infection is pegylated interferon alpha; however, response rates to this therapy are poor. A better knowledge of HDV–host cell interaction will help with the identification of novel therapeutic targets, which are urgently needed. Animal models like hepadnavirus-infected chimpanzees or the eastern woodchuck have been of great value for the characterization of HDV chronic infection. Recently, more practical animal models in which to perform a deeper study of host virus interactions and to evaluate new therapeutic strategies have been developed. Therefore, the main focus of this review is to discuss the current knowledge about HDV host interactions obtained from cell culture and animal models. PMID:25686091

  18. Leveraging H1N1 infection transmission modeling with proximity sensor microdata

    PubMed Central

    2012-01-01

    Background The contact networks between individuals can have a profound impact on the evolution of an infectious outbreak within a network. The impact of the interaction between contact network and disease dynamics on infection spread has been investigated using both synthetic and empirically gathered micro-contact data, establishing the utility of micro-contact data for epidemiological insight. However, the infection models tied to empirical contact data were highly stylized and were not calibrated or compared against temporally coincident infection rates, or omitted critical non-network based risk factors such as age or vaccination status. Methods In this paper we present an agent-based simulation model firmly grounded in disease dynamics, incorporating a detailed characterization of the natural history of infection, and 13 weeks worth of micro-contact and participant health and risk factor information gathered during the 2009 H1N1 flu pandemic. Results We demonstrate that the micro-contact data-based model yields results consistent with the case counts observed in the study population, derive novel metrics based on the logarithm of the time degree for evaluating individual risk based on contact dynamic properties, and present preliminary findings pertaining to the impact of internal network structures on the spread of disease at an individual level. Conclusions Through the analysis of detailed output of Monte Carlo ensembles of agent based simulations we were able to recreate many possible scenarios of infection transmission using an empirically grounded dynamic contact network, providing a validated and grounded simulation framework and methodology. We confirmed recent findings on the importance of contact dynamics, and extended the analysis to new measures of the relative risk of different contact dynamics. Because exponentially more time spent with others correlates to a linear increase in infection probability, we conclude that network dynamics have an

  19. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

    PubMed

    Mellado-Sanchez, Gabriela; Ramirez, Karina; Drachenberg, Cinthia B; Diaz-McNair, Jovita; Rodriguez, Ana L; Galen, James E; Nataro, James P; Pasetti, Marcela F

    2013-03-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings.

  20. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

    PubMed

    Mellado-Sanchez, Gabriela; Ramirez, Karina; Drachenberg, Cinthia B; Diaz-McNair, Jovita; Rodriguez, Ana L; Galen, James E; Nataro, James P; Pasetti, Marcela F

    2013-03-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. PMID:23195858

  1. Pharmacokinetics and dose response of anti-TB drugs in rat infection model of tuberculosis.

    PubMed

    Kumar, Naveen; Vishwas, K G; Kumar, Mahesh; Reddy, Jitendar; Parab, Manish; Manikanth, C L; Pavithra, B S; Shandil, R K

    2014-05-01

    Robust and physiologically relevant infection models are required to investigate pharmacokinetic-pharmacodynamic (PK/PD) correlations for anti-tuberculosis agents at preclinical discovery. We have validated an inhalation-based rat infection model of tuberculosis harbouring mycobacteria in a replicating state, that is suitable for investigating pharmacokinetics and drug action of anti-tubercular agents. A reproducible and actively replicating lung infection was established in Wistar rats by inhalation of a series of graded inocula of Mycobacterium tuberculosis. Following an initial instillation of ∼10(5) log10 CFU/lung, M. tuberculosis grew logarithmically for the first 3 weeks, and then entered into a chronic phase with no net increase in pulmonary bacterial loads. Dose response of front-line anti-TB drugs was investigated following pharmacokinetic measurements in the plasma of infected rats. Rifampicin, Isoniazid, and Ethambutol dosed per orally exhibited bactericidality and good dose response with maximal effect of 5.66, 4.66, and 4.80 log10 CFU reductions in the lungs, respectively. In contrast, Pyrazinamide was merely bacteriostatic with 1.92 log10 CFU/lung reduction and did not reduce the bacterial burden beyond the initial bacterial loads present at beginning of treatment in spite of high Pyrazinamide blood levels. Rat infection model with actively replicating bacilli provides a physiologically distinct and pharmacologically relevant model that can be exploited to distinguish investigational compounds in to bacteriostatic or bactericidal scaffolds. We propose that this rat infection model though need more drug substance, can be used in early discovery settings to investigate pharmacology of novel anti-tubercular agents for the treatment of active pulmonary tuberculosis.

  2. Future challenges for clinical care of an ageing population infected with HIV: a modelling study

    PubMed Central

    Smit, Mikaela; Brinkman, Kees; Geerlings, Suzanne; Smit, Colette; Thyagarajan, Kalyani; Sighem, Ard van; de Wolf, Frank; Hallett, Timothy B

    2015-01-01

    Summary Background The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. Methods We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs—including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies—and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. Findings Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug–drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. Interpretation The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence

  3. A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection

    PubMed Central

    Baccarella, Alyssa; Craft, Joshua F.; Boyle, Michelle J.; McIntyre, Tara I.; Wood, Matthew D.; Thorn, Kurt S.; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y.; Pearman, Emily; Pham, Jennifer; Tang, Jia J.; Boon, Louis; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.; Kim, Charles C.

    2016-01-01

    In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. PMID:27583554

  4. A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection.

    PubMed

    Fontana, Mary F; Baccarella, Alyssa; Craft, Joshua F; Boyle, Michelle J; McIntyre, Tara I; Wood, Matthew D; Thorn, Kurt S; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y; Pearman, Emily; Pham, Jennifer; Tang, Jia J; Boon, Louis; Kamya, Moses R; Dorsey, Grant; Feeney, Margaret E; Kim, Charles C

    2016-01-01

    In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. PMID:27583554

  5. A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection.

    PubMed

    Baseler, L; de Wit, E; Feldmann, H

    2016-05-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.

  6. Interferon α/β receptor knockout mice as a model to study bluetongue virus infection.

    PubMed

    Ortego, Javier; de la Poza, Francisco; Marín-López, Alejandro

    2014-03-01

    Bluetongue is an arthropod-borne disease caused by a virus of the genus Orbivirus, the bluetongue virus (BTV), which affects ruminant livestock such as cattle, sheep, and goats and wild ruminants such as deer, and camelids. Recently, adult mice with gene knockouts of the interferon α/β receptor (IFNAR-/-) have been described as a model of lethal BTV infection. IFNAR(-/-) mice are highly susceptible to BTV-1, BTV-4 and BTV-8 infection when the virus is administered intravenously or subcutaneosuly. Disease progression and pathogenesis closely mimics signs of bluetongue disease in ruminants. In the present paper we review the studies where IFNAR(-/-) mice have been used as an animal model to study BTV transmission, pathogenesis, virulence, and protective efficacy of inactivated and new recombinant marker BTV vaccines. Furthermore, we report new data on protective efficacy of different strategies of BTV vaccination and also on induction of interferon α/β and proinflammatory immune responses in IFNAR(-/-) mice infected with BTV.

  7. Models for an arenavirus infection in a rodent population: consequences of horizontal, vertical and sexual transmission.

    PubMed

    Banerjee, Chandrani; Allen, Linda J S; Salazar-Bravo, Jorge

    2008-10-01

    Arenaviruses are associated with rodent-transmitted diseases in humans. Five arenaviruses are known to cause human illness: Lassa virus, Junin virus, Machupo virus, Guanarito virus and Sabia virus. In this investigation, we model the spread of Machupo virus in its rodent host Calomys callosus. Machupo virus infection in humans is known as Bolivian hemorrhagic fever (BHF) which has a mortality rate of approximately 5-30% [31]. Machupo virus is transmitted among rodents through horizontal (direct contact), vertical (infected mother to offspring) and sexual transmission. The immune response differs among rodents infected with Machupo virus. Either rodents develop immunity and recover (immunocompetent) or they do not develop immunity and remain infected (immunotolerant). We formulate a general deterministic model for male and female rodents consisting of eight differential equations, four for females and four for males. The four states represent susceptible, immunocompetent, immunotolerant and recovered rodents, denoted as S, I( t), I( c)and R, respectively. A unique disease-free equilibrium (DFE) is shown to exist and a basic reproduction number R( 0)is computed using the next generation matrix approach. The DFE is shown to be locally asymptotically stable if R(0) < 1and unstable if R( 0) > 1. Special cases of the general model are studied, where there is only one immune stage, either I(t) or I(c). In the first model, SI(c)R( c), it is assumed that all infected rodents are immunocompetent and recover. In the second model, SI(t), it is assumed that all infected rodents are immunotolerant. For each of these models, the basic reproduction numbers are computed and their relationship to the basic reproduction number of the general model determined. For the SI( t)model, it is shown that bistability may occur, the DFE and an enzootic equilibrium, with all rodents infectious, are locally asymptotically stable for the same set of parameter values. A simplification of the SI( t)model

  8. Apoptosis and cell proliferation in the mouse model of embryonic death induced by Tritrichomonas foetus infection.

    PubMed

    Woudwyk, Mariana A; Zanuzzi, Carolina N; Nishida, Fabián; Gimeno, Eduardo J; Soto, Pedro; Monteavaro, Cristina E; Barbeito, Claudio G

    2015-09-01

    Bovine tritrichomonosis is a sexually transmitted disease caused by the protozoon Tritrichomonas foetus and characterised by embryonic-death and abortion. During pregnancy, the processes of cell proliferation and death play a crucial role for blastocyst implantation and the subsequent maintenance of early pregnancy, and their misbalance may lead to the abortion. In this study, we aimed to investigate whether cell proliferation and death may be altered during tritrichomonosis. For this purpose, we used pregnant BALB/c mice as an alternative experimental animal model that has successfully reproduced the infection. We analysed the immunohistochemical expression of active caspase-3 and proliferating cell nuclear (PCNA) antigens in the endometrium of infected mice. We found an increase in the number of caspase-3 positive cells in infected mice that were not pregnant at the necropsy. Besides, the number of positive proliferating cells increased in the uterine luminal epithelium of infected animals killed at 5-7 days post coitum (dpc). Pregnant infected mice killed at 8-11 dpc showed higher proliferation than control animals. We suggest that the cytopathic effect induced by T. foetus in the uteri of infected mice may induce the apoptosis of the epithelial cells and, as a result, promote a compensatory proliferative response. The information described here will be helpful to further study the pathogenesis of the bovine tritrichomonosis. PMID:26028409

  9. Compartmentalized intrathecal immunoglobulin synthesis during HIV infection - a model of chronic CNS inflammation?

    PubMed

    Bonnan, Mickael; Barroso, Bruno; Demasles, Stéphanie; Krim, Elsa; Marasescu, Raluca; Miquel, Marie

    2015-08-15

    HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood-brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis. PMID:26198917

  10. Determination of original infection source of H7N9 avian influenza by dynamical model.

    PubMed

    Zhang, Juan; Jin, Zhen; Sun, Gui-Quan; Sun, Xiang-Dong; Wang, You-Ming; Huang, Baoxu

    2014-01-01

    H7N9, a newly emerging virus in China, travels among poultry and human. Although H7N9 has not aroused massive outbreaks, recurrence in the second half of 2013 makes it essential to control the spread. It is believed that the most effective control measure is to locate the original infection source and cut off the source of infection from human. However, the original infection source and the internal transmission mechanism of the new virus are not totally clear. In order to determine the original infection source of H7N9, we establish a dynamical model with migratory bird, resident bird, domestic poultry and human population, and view migratory bird, resident bird, domestic poultry as original infection source respectively to fit the true dynamics during the 2013 pandemic. By comparing the date fitting results and corresponding Akaike Information Criterion (AIC) values, we conclude that migrant birds are most likely the original infection source. In addition, we obtain the basic reproduction number in poultry and carry out sensitivity analysis of some parameters. PMID:24786135

  11. Determination of Original Infection Source of H7N9 Avian Influenza by Dynamical Model

    NASA Astrophysics Data System (ADS)

    Zhang, Juan; Jin, Zhen; Sun, Gui-Quan; Sun, Xiang-Dong; Wang, You-Ming; Huang, Baoxu

    2014-05-01

    H7N9, a newly emerging virus in China, travels among poultry and human. Although H7N9 has not aroused massive outbreaks, recurrence in the second half of 2013 makes it essential to control the spread. It is believed that the most effective control measure is to locate the original infection source and cut off the source of infection from human. However, the original infection source and the internal transmission mechanism of the new virus are not totally clear. In order to determine the original infection source of H7N9, we establish a dynamical model with migratory bird, resident bird, domestic poultry and human population, and view migratory bird, resident bird, domestic poultry as original infection source respectively to fit the true dynamics during the 2013 pandemic. By comparing the date fitting results and corresponding Akaike Information Criterion (AIC) values, we conclude that migrant birds are most likely the original infection source. In addition, we obtain the basic reproduction number in poultry and carry out sensitivity analysis of some parameters.

  12. Mimicking Neural Stem Cell Niche by Biocompatible Substrates

    PubMed Central

    Regalado-Santiago, Citlalli; Juárez-Aguilar, Enrique; Olivares-Hernández, Juan David; Tamariz, Elisa

    2016-01-01

    Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to building in vitro models that include the relevant components of the in vivo niche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for the in vitro and in vivo mimicking of extracellular NSCs conditions. PMID:26880934

  13. An In Vitro Model of the Human Colon: Studies of Intestinal Biofilms and Clostridium difficile Infection.

    PubMed

    Crowther, Grace S; Wilcox, Mark H; Chilton, Caroline H

    2016-01-01

    The in vitro gut model is an invaluable research tool to study indigenous gut microbiota communities, the behavior of pathogenic organisms, and the therapeutic and adverse effect of antimicrobial administration on these communities. The model has been validated against the intestinal contents of sudden death victims to reflect the physicochemical and microbiological conditions of the proximal to distal colon, and has been extensively used to investigate the interplay between gut microbiota populations, antibiotic exposure, and Clostridium difficile infection. More recently the gut model has been adapted to additionally model intestinal biofilm. Here we describe the structure, assembly, and application of the biofilm gut model. PMID:27507345

  14. The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

    PubMed Central

    Cross, Robert W.; Mire, Chad E.; Borisevich, Viktoriya; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo. PMID:27354371

  15. Modelling sexually transmitted infections: less is usually more for informing public health policy.

    PubMed

    Regan, David G; Wilson, David P

    2008-03-01

    Mathematical models have been used to investigate the dynamics of infectious disease transmission since Bernoulli's smallpox modelling in 1760. Their use has become widespread for exploring how epidemics can be prevented or contained. Here we discuss the importance of modelling the dynamics of sexually transmitted infections, the technology-driven dichotomy in methodology, and the need to 'keep it simple' to explore sensitivity, to link the models to reality and to provide understandable mechanistic explanations for real-world policy-makers. The aim of models, after all, is to influence or change public health policy by providing rational forecasting based on sound scientific principles. PMID:17915269

  16. Localized bacterial infection in a distributed model for tissue inflammation.

    PubMed

    Lauffenburger, D A; Kennedy, C R

    1983-01-01

    Phagocyte motility and chemotaxis are included in a distributed mathematical model for the inflammatory response to bacterial invasion of tissue. Both uniform and non-uniform steady state solutions may occur for the model equations governing bacteria and phagocyte densities in a macroscopic tissue region. The non-uniform states appear to be more dangerous because they allow large bacteria densities concentrated in local foci, and in some cases greater total bacteria and phagocyte populations. Using a linear stability analysis, it is shown that a phagocyte chemotactic response smaller than a critical value can lead to a non-uniform state, while a chemotactic response greater than this critical value stabilizes the uniform state. This result is the opposite of that found for the role of chemotaxis in aggregation of slimemold amoebae because, in the inflammatory response, the chemotactic population serves as an inhibitor rather than an activator. We speculate that these non-uniform steady states could be related to the localized cell aggregation seen in chronic granulomatous inflammation. The formation of non-uniform states is not necessarily a consequence of defective phagocyte chemotaxis, however. Rather, certain values of the kinetic parameters can yield values for the critical chemotactic response which are greater than the normal response. Numerical computations of the transient inflammatory response to bacterial challenge are presented, using parameter values estimated from the experimental literature wherever possible. PMID:6827185

  17. Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

    PubMed

    Saric, Jasmina; Li, Jia V; Wang, Yulan; Keiser, Jennifer; Veselkov, Kirill; Dirnhofer, Stephan; Yap, Ivan K S; Nicholson, Jeremy K; Holmes, Elaine; Utzinger, Jürg

    2009-08-01

    Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning (1)H NMR spectroscopy and biofluids measured by applying conventional (1)H NMR spectroscopy. Spectral data were analyzed via principal component analysis, partial least-squares-derived methods and hierarchical projection analyses. Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, for example, alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore

  18. Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella

    PubMed Central

    2013-01-01

    Background Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella. Results We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone. Conclusions G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains. PMID:24083556

  19. A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation

    PubMed Central

    Kupz, Andreas; Zedler, Ulrike; Stäber, Manuela

    2016-01-01

    Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)+ individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4+ T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4+ cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4+ T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8+ memory T cells, natural killer (NK) cells and double-negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection. PMID:27391012

  20. Characterization of Burkholderia pseudomallei Strains Using a Murine Intraperitoneal Infection Model and In Vitro Macrophage Assays

    PubMed Central

    Welkos, Susan L.; Klimko, Christopher P.; Kern, Steven J.; Bearss, Jeremy J.; Bozue, Joel A.; Bernhards, Robert C.; Trevino, Sylvia R.; Waag, David M.; Amemiya, Kei; Worsham, Patricia L.; Cote, Christopher K.

    2015-01-01

    Burkholderia pseudomallei, the etiologic agent of melioidosis, is a gram-negative facultative intracellular bacterium. This bacterium is endemic in Southeast Asia and Northern Australia and can infect humans and animals by several routes. It has also been estimated to present a considerable risk as a potential biothreat agent. There are currently no effective vaccines for B. pseudomallei, and antibiotic treatment can be hampered by nonspecific symptomology, the high incidence of naturally occurring antibiotic resistant strains, and disease chronicity. Accordingly, there is a concerted effort to better characterize B. pseudomallei and its associated disease. Before novel vaccines and therapeutics can be tested in vivo, a well characterized animal model is essential. Previous work has indicated that mice may be a useful animal model. In order to develop standardized animal models of melioidosis, different strains of bacteria must be isolated, propagated, and characterized. Using a murine intraperitoneal (IP) infection model, we tested the virulence of 11 B. pseudomallei strains. The IP route offers a reproducible way to rank virulence that can be readily reproduced by other laboratories. This infection route is also useful in distinguishing significant differences in strain virulence that may be masked by the exquisite susceptibility associated with other routes of infection (e.g., inhalational). Additionally, there were several pathologic lesions observed in mice following IP infection. These included varisized abscesses in the spleen, liver, and haired skin. This model indicated that commonly used laboratory strains of B. pseudomallei (i.e., K96243 and 1026b) were significantly less virulent as compared to more recently acquired clinical isolates. Additionally, we characterized in vitro strain-associated differences in virulence for macrophages and described a potential inverse relationship between virulence in the IP mouse model of some strains and in the

  1. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection.

    PubMed

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-08-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  2. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

    SciTech Connect

    Guillaume, Vanessa; Wong, K. Thong; Looi, R.Y.; Georges-Courbot, Marie-Claude; Barrot, Laura; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2009-05-10

    Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeV if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.

  3. Early antibiotics and debridement independently reduce infection in an open fracture model.

    PubMed

    Penn-Barwell, J G; Murray, C K; Wenke, J C

    2012-01-01

    Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment. We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis. No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.

  4. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

    PubMed Central

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-01-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the “gold standard” for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  5. Exposure to pairs of Aeromonas strains enhances virulence in the Caenorhabditis elegans infection model.

    PubMed

    Mosser, Thomas; Talagrand-Reboul, Emilie; Colston, Sophie M; Graf, Joerg; Figueras, Maria J; Jumas-Bilak, Estelle; Lamy, Brigitte

    2015-01-01

    Aeromonad virulence remains poorly understood, and is difficult to predict from strain characteristics. In addition, infections are often polymicrobial (i.e., are mixed infections), and 5-10% of such infections include two distinct aeromonads, which has an unknown impact on virulence. In this work, we studied the virulence of aeromonads recovered from human mixed infections. We tested them individually and in association with other strains with the aim of improving our understanding of aeromonosis. Twelve strains that were recovered in pairs from six mixed infections were tested in a virulence model of the worm Caenorhabditis elegans. Nine isolates were weak worm killers (median time to death, TD50, ≥7 days) when administered alone. Two pairs showed enhanced virulence, as indicated by a significantly shortened TD50 after co-infection vs. infection with a single strain. Enhanced virulence was also observed for five of the 14 additional experimental pairs, and each of these pairs included one strain from a natural synergistic pair. These experiments indicated that synergistic effects were frequent and were limited to pairs that were composed of strains belonging to different species. The genome content of virulence-associated genes failed to explain virulence synergy, although some virulence-associated genes that were present in some strains were absent from their companion strain (e.g., T3SS). The synergy observed in virulence when two Aeromonas isolates were co-infected stresses the idea that consideration should be given to the fact that infection does not depend only on single strain virulence but is instead the result of a more complex interaction between the microbes involved, the host and the environment. These results are of interest for other diseases in which mixed infections are likely and in particular for water-borne diseases (e.g., legionellosis, vibriosis), in which pathogens may display enhanced virulence in the presence of the right partner. This

  6. Exposure to pairs of Aeromonas strains enhances virulence in the Caenorhabditis elegans infection model

    PubMed Central

    Mosser, Thomas; Talagrand-Reboul, Emilie; Colston, Sophie M.; Graf, Joerg; Figueras, Maria J.; Jumas-Bilak, Estelle; Lamy, Brigitte

    2015-01-01

    Aeromonad virulence remains poorly understood, and is difficult to predict from strain characteristics. In addition, infections are often polymicrobial (i.e., are mixed infections), and 5–10% of such infections include two distinct aeromonads, which has an unknown impact on virulence. In this work, we studied the virulence of aeromonads recovered from human mixed infections. We tested them individually and in association with other strains with the aim of improving our understanding of aeromonosis. Twelve strains that were recovered in pairs from six mixed infections were tested in a virulence model of the worm Caenorhabditis elegans. Nine isolates were weak worm killers (median time to death, TD50, ≥7 days) when administered alone. Two pairs showed enhanced virulence, as indicated by a significantly shortened TD50 after co-infection vs. infection with a single strain. Enhanced virulence was also observed for five of the 14 additional experimental pairs, and each of these pairs included one strain from a natural synergistic pair. These experiments indicated that synergistic effects were frequent and were limited to pairs that were composed of strains belonging to different species. The genome content of virulence-associated genes failed to explain virulence synergy, although some virulence-associated genes that were present in some strains were absent from their companion strain (e.g., T3SS). The synergy observed in virulence when two Aeromonas isolates were co-infected stresses the idea that consideration should be given to the fact that infection does not depend only on single strain virulence but is instead the result of a more complex interaction between the microbes involved, the host and the environment. These results are of interest for other diseases in which mixed infections are likely and in particular for water-borne diseases (e.g., legionellosis, vibriosis), in which pathogens may display enhanced virulence in the presence of the right partner. This

  7. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

    PubMed Central

    Anderson, Christopher S.; DeDiego, Marta L.; Topham, David J.; Thakar, Juilee

    2016-01-01

    Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection. PMID:26981147

  8. Modeling the Impact of Breast-Feeding by HIV-Infected Women on Child Survival.

    ERIC Educational Resources Information Center

    Heymann, Sally Jody

    1990-01-01

    Models the survival outcomes of children in developing countries born to women infected with human immunodeficiency virus (HIV) who are breast-fed, bottle-fed, and wet-nursed. Uses decision analysis to assess the relative risk of child mortality from HIV transmission and non-HIV causes associated with different methods of feeding. (FMW)

  9. Zika in the Brain: New Models Shed Light on Viral Infection.

    PubMed

    Hickman, Heather D; Pierson, Theodore C

    2016-08-01

    The current Zika virus (ZIKV) outbreak is associated with high numbers of human congenital birth defects, yet it has been unclear how ZIKV infection during pregnancy causes these abnormalities. Three new mouse models now show that ZIKV crosses the placenta and replicates in the brains of fetal mice.

  10. Zika in the Brain: New Models Shed Light on Viral Infection.

    PubMed

    Hickman, Heather D; Pierson, Theodore C

    2016-08-01

    The current Zika virus (ZIKV) outbreak is associated with high numbers of human congenital birth defects, yet it has been unclear how ZIKV infection during pregnancy causes these abnormalities. Three new mouse models now show that ZIKV crosses the placenta and replicates in the brains of fetal mice. PMID:27345865

  11. Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections

    PubMed Central

    Manickam, Cordelia; Reeves, R. Keith

    2014-01-01

    Hepatitis C virus (HCV) infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies this disease still poses a significant threat due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors toward chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease with a primary focus on GB virus B (GBV-B) infection of New World primates that recapitulates the dual Hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies. PMID:25538700

  12. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection.

    PubMed

    Anderson, Christopher S; DeDiego, Marta L; Topham, David J; Thakar, Juilee

    2016-01-01

    Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

  13. A reusable perfusion supporting tissue-mimicking material for ultrasound hyperthermia phantoms.

    PubMed

    Chin, R B; Madsen, E L; Zagzebski, J A; Jadvar, H; Wu, X K; Frank, G R

    1990-01-01

    A new ultrasonically and thermodynamically tissue-mimicking material is reported. The material is well suited for use in phantoms for testing ultrasound hyperthermia systems or related predictive models. Controlled convective heat transfer effects, mimicking to some extent perfusive heat transfer in tissues, can be instituted in the material with appropriate fluid sources and sinks. The material consists of closely packed agar spheres varying in diameters from 0.3-3.6 mm. The interstitial space between spheres is filled with 10% n-propanol solution. The material has two practical advantages over the solid-gel-type tissue-mimicking materials. The first advantage is that it allows rapid return of a hyperthermia phantom to thermal equilibrium following a heating test by rapid circulation of the perfusion fluid. The second advantage is that the material is in a "liquid" form. It can be easily siphoned in and out of phantom containers of any geometric shape for different purposes without change in its physical properties. Methods for measuring ultrasonic and thermodynamic properties of the material and the results of the measurements are reported. The physical parameters measured are the intensity attenuation and absorption coefficients, the ultrasonic speed, the thermal conductivity, specific-heat capacity and the mass density. Temperature measurements in a hyperthermia phantom made of the material are also reported. PMID:2385195

  14. Assessing Mathematical Models of Influenza Infections Using Features of the Immune Response

    PubMed Central

    Dobrovolny, Hana M.; Reddy, Micaela B.; Kamal, Mohamed A.; Rayner, Craig R.; Beauchemin, Catherine A. A.

    2013-01-01

    The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza. PMID:23468916

  15. Inactivation of the CovR/S virulence regulator impairs infection in an improved murine model of Streptococcus pyogenes naso-pharyngeal infection.

    PubMed

    Alam, Faraz M; Turner, Claire E; Smith, Ken; Wiles, Siouxsie; Sriskandan, Shiranee

    2013-01-01

    Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection.

  16. A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

    PubMed Central

    Morris, C. Paul; Evans, Holly; Larsen, Sasha E.

    2013-01-01

    SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models. PMID:23824365

  17. A comprehensive, model-based review of vaccine and repeat infection trials for filariasis.

    PubMed

    Morris, C Paul; Evans, Holly; Larsen, Sasha E; Mitre, Edward

    2013-07-01

    SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

  18. Investigation of Host and Pathogen Contributions to Infectious Colitis Using the Citrobacter rodentium Mouse Model of Infection.

    PubMed

    Bosman, Else S; Chan, Justin M; Bhullar, Kirandeep; Vallance, Bruce A

    2016-01-01

    Citrobacter rodentium is used as a model organism to study enteric bacterial infections in mice. Infection occurs via the oral-fecal route and results in the pathogen forming attaching and effacing lesions on infected epithelial cells. Moreover, infection leads to a subsequent host-mediated form of colitis. C. rodentium infection is thus an excellent model to study infectious colitis in vivo, while the ability to genetically manipulate C. rodentium virulence genes provides the opportunity to develop clear insights into the pathogenesis of this and related infectious microbes. This chapter outlines the basic techniques involved in setting up a C. rodentium infection in mice and several different methodologies to assess the severity of the infection.

  19. A Bovine Model of Respiratory Chlamydia psittaci Infection: Challenge Dose Titration

    PubMed Central

    Reinhold, Petra; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Vogel, Anette; Lambertz, Jacqueline; Rothe, Michael; Rüttger, Anke; Schubert, Evelyn; Sachse, Konrad

    2012-01-01

    This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2–3 months via bronchoscope at four different challenge doses from 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 induced fever, tachypnea, dry cough, and tachycardia that became apparent 2–3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 109 ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host

  20. On the dynamics of SEIRS epidemic model with transport-related infection.

    PubMed

    Denphedtnong, Adisak; Chinviriyasit, Settapat; Chinviriyasit, Wirawan

    2013-10-01

    Transportation amongst cities is found as one of the main factors which affect the outbreak of diseases. To understand the effect of transport-related infection on disease spread, an SEIRS (Susceptible, Exposed, Infectious, Recovered) epidemic model for two cities is formulated and analyzed. The epidemiological threshold, known as the basic reproduction number, of the model is derived. If the basic reproduction number is below unity, the disease-free equilibrium is locally asymptotically stable. Thus, the disease can be eradicated from the community. There exists an endemic equilibrium which is locally asymptotically stable if the reproduction number is larger than unity. This means that the disease will persist within the community. The results show that transportation among regions will change the disease dynamics and break infection out even if infectious diseases will go to extinction in each isolated region without transport-related infection. In addition, the result shows that transport-related infection intensifies the disease spread if infectious diseases break out to cause an endemic situation in each region, in the sense of that both the absolute and relative size of patients increase. Further, the formulated model is applied to the real data of SARS outbreak in 2003 to study the transmission of disease during the movement between two regions. The results show that the transport-related infection is effected to the number of infected individuals and the duration of outbreak in such the way that the disease becomes more endemic due to the movement between two cities. This study can be helpful in providing the information to public health authorities and policy maker to reduce spreading disease when its occurs.

  1. Clinical Features of Bacterial Vaginosis in a Murine Model of Vaginal Infection with Gardnerella vaginalis

    PubMed Central

    Gilbert, Nicole M.; Lewis, Warren G.; Lewis, Amanda L.

    2013-01-01

    Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and Gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells). G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and associated complications

  2. A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses.

    PubMed

    Yang, Xingdong; Li, Guohua; Wen, Ke; Bui, Tammy; Liu, Fangning; Kocher, Jacob; Jortner, Bernard S; Vonck, Marlice; Pelzer, Kevin; Deng, Jie; Zhu, Runan; Li, Yuyun; Qian, Yuan; Yuan, Lijuan

    2014-05-01

    Vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. Here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain BJ110, which has a C4 genotype. Porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. Oral and combined oral-nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×10(8) fluorescence forming units (FFU) resulted in shedding up to 18 days post-infection, with viral titers in rectal swab samples peaking at 2.22×10(8) viral RNA copies/mL. Viral capsid proteins were detected in enterocytes within the small intestines on post-infection days (PIDs) 7 and 14. Additionally, viral RNA was detected in intestinal and extra-intestinal tissues, including the central nervous system, the lung and cardiac muscle. The infected neonatal gnotobiotic pigs developed fever, forelimb weakness, rapid breathing and some hand, foot and mouth disease symptoms. Flow cytometry analysis revealed increased frequencies of both CD4(+) and CD8(+) IFN-γ-producing T cells in the brain and the blood on PID 14, but reduced frequencies were observed in the lung. Furthermore, high titers of serum virus-neutralizing antibodies were generated in both orally and combined oral-nasally infected pigs on PIDs 7, 14, 21 and 28. Together, these results demonstrate that neonatal gnotobiotic pigs represent a novel animal model for evaluating vaccines for human enterovirus 71 and for understanding the pathogenesis of this virus and the associated immune responses. PMID:26038741

  3. Neural basis of psychosis-related behaviour in the infection model of schizophrenia.

    PubMed

    Meyer, Urs; Feldon, Joram

    2009-12-01

    Maternal infection during pregnancy is a notable risk factor for the offspring to develop severe neuropsychiatric disorders, including schizophrenia. One prevalent hypothesis suggests that infection-induced disruption of early prenatal brain development predisposes the organism for long-lasting structural and functional brain abnormalities, leading to the emergence of psychopathological behaviour in adulthood. The feasibility of this causal link has received considerable support from several experimental models established in both rats and mice. In this review, we provide an integrative summary of the long-term neuropathological consequences of prenatal exposure to infection and/or inflammation as identified in various experimental models of prenatal immune challenge. In addition, we highlight how abnormalities in distinct brain areas and neurotransmitter systems following prenatal immune activation may provide a neural basis for the emergence of specific forms of psychosis-related behaviour. Specifically, we suggest that prenatal infection-induced imbalances in the mesolimibic and mesocortical dopamine pathways may constitute critical neural mechanisms for disturbances in sensorimotor gating, abnormalities in selective associative learning and hypersensitivity to psychostimulant drugs. On the other hand, the emergence of working memory deficiency following prenatal immune challenge may be crucially linked to the concomitant disruption of GABAergic and glutamatergic functions in prefrontal cortical and hippocampal structures. Notably, many of the identified neuronal abnormalities are directly implicated in the neuropathology of schizophrenia. The findings from prenatal infection models of schizophrenia thus provide considerable experimental evidence for the assumption that prenatal exposure to infection and/or inflammation is a relevant environmental link to specific neuronal abnormalities underlying psychosis-related behaviour in humans. PMID:19154759

  4. A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice

    PubMed Central

    Milligan, Gregg N.; Sarathy, Vanessa V.; Infante, Ernesto; Li, Li; Campbell, Gerald A.; Beatty, P. Robert; Harris, Eva; Barrett, Alan D. T.; Bourne, Nigel

    2015-01-01

    Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this