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Sample records for infection model mimicking

  1. Novel Mouse Model of Chronic Pseudomonas aeruginosa Lung Infection Mimicking Cystic Fibrosis

    PubMed Central

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, PeterØstrup; Stub, Charlotte; Hentzer, Morten; Molin, Søren; Ciofu, Oana; Givskov, Michael; Johansen, Helle Krogh; Høiby, Niels

    2005-01-01

    Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (CftrtmlUnc−/−) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoid P. aeruginosa, the host, and antibacterial therapy. PMID:15784597

  2. A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.

    PubMed

    Wang, Lei; Cao, Min; Wei, Qing Lu; Zhao, Zhong Hua; Xiang, Qin; Wang, Hui Juan; Zhang, Hua Tang; Lai, Guo Qi

    2017-01-01

    Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem. HBV e antigen (HBeAg)-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA). The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection. Persistence of the HBeAg-negative infection was monitored at predetermined time points using HBV-specific markers including HBV surface antigen (HBsAg), HBeAg, and HBV core antigen (HBcAg) as well as DNA copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage. HBsAg levels increased up to 1 week, at which point levels peaked and dropped quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more than 10 weeks. High numbers of HBV DNA copies were detected in the serum and liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected with HBeAg-negative HBV throughout the study period. These results demonstrate the first successful establishment of a model of HBeAg-negative HBV-persistent infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the infection persistence and levels of serum virological and biochemical markers were approximately equal in the model mice. This model will be useful for mechanistic studies on HBeAg-negative HBV infection and will facilitate the evaluation of new antiviral drugs.

  3. Nematode infection mimicking paratesticular malignancy.

    PubMed

    Kallampallil, Jins; Wood, Sarah J; O'Dempsey, Timothy; Craigie, Ross J

    2013-12-10

    Paratesticular swellings pose a diagnostic dilemma due to concerns over malignancy. We present a case of paratesticular swelling in a 13-year-old boy as a result of Dirofilaria immitis infection. The boy presented with a 2-month history of right testicular discomfort associated with an irregular mass within the scrotum.

  4. Model molecules mimicking asphaltenes.

    PubMed

    Sjöblom, Johan; Simon, Sébastien; Xu, Zhenghe

    2015-04-01

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

  5. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host–pathogen interactions in cystic fibrosis

    PubMed Central

    MOSER, CLAUS; VAN GENNIP, MARIA; BJARNSHOLT, THOMAS; JENSEN, PETER ØSTRUP; LEE, BAOLERI; HOUGEN, HANS PETTER; CALUM, HENRIK; CIOFU, OANA; GIVSKOV, MICHAEL; MOLIN, SØREN; HØIBY, NIELS

    2009-01-01

    The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno- and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year-long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein-2 (MIP-2) and granulocyte colony-stimulating factor (G-CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP-2 and G-CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non-mucoid phenotypes. PMID:19239431

  6. 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

  7. 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.

  8. Undigested Pills in Stool Mimicking Parasitic Infection.

    PubMed

    Mir, Fazia; Achakzai, Ilyas; Ibdah, Jamal A; Tahan, Veysel

    2017-01-01

    Background. Orally ingested medications now come in both immediate release and controlled release preparations. Controlled release preparations were developed by pharmaceutical companies to improve compliance and decrease frequency of pill ingestion. Case Report. A 67-year-old obese male patient presented to our clinic with focal abdominal pain that had been present 3 inches below umbilicus for the last three years. This pain was not associated with any trauma or recent heavy lifting. Upon presentation, the patient reported that for the last two months he started to notice pearly oval structures in his stool accompanying his chronic abdominal pain. This had coincided with initiation of his nifedipine pills for his hypertension. He reported seeing these undigested pills daily in his stool. Conclusion. The undigested pills may pose a cause of concern for both patients and physicians alike, as demonstrated in this case report, because they can mimic a parasitic infection. This can result in unnecessary extensive work-up. It is important to review the medication list for extended release formulations and note that the outer shell can be excreted whole in the stool.

  9. Undigested Pills in Stool Mimicking Parasitic Infection

    PubMed Central

    Mir, Fazia; Achakzai, Ilyas; Ibdah, Jamal A.

    2017-01-01

    Background. Orally ingested medications now come in both immediate release and controlled release preparations. Controlled release preparations were developed by pharmaceutical companies to improve compliance and decrease frequency of pill ingestion. Case Report. A 67-year-old obese male patient presented to our clinic with focal abdominal pain that had been present 3 inches below umbilicus for the last three years. This pain was not associated with any trauma or recent heavy lifting. Upon presentation, the patient reported that for the last two months he started to notice pearly oval structures in his stool accompanying his chronic abdominal pain. This had coincided with initiation of his nifedipine pills for his hypertension. He reported seeing these undigested pills daily in his stool. Conclusion. The undigested pills may pose a cause of concern for both patients and physicians alike, as demonstrated in this case report, because they can mimic a parasitic infection. This can result in unnecessary extensive work-up. It is important to review the medication list for extended release formulations and note that the outer shell can be excreted whole in the stool. PMID:28255472

  10. Hepatitis A infection mimicking adult onset Still's disease.

    PubMed

    Sridharan, S; Mossad, S; Hoffman, G

    2000-07-01

    Fever, rash, and arthritis may be components of the prodrome of viral hepatitis. In the absence of jaundice and abnormal liver function tests, this form of polyarthritis is easily confused with primary autoimmune diseases. Whereas the association of systemic illness with musculoskeletal symptoms and numerous viral infections is well known, such an association with hepatitis A has only been rarely reported. We describe a case of hepatitis A infection mimicking adult onset Still's disease, and review the pathogenesis and differential diagnosis of Still's disease and the extraarticular manifestations of hepatitis.

  11. Post-Laminectomy Wound Infections: Colonized Seromas Mimicking Wound Infections.

    PubMed

    Cunha, Burke A; Abruzzo, Eileen D; Schoch, Paul E

    2014-02-14

    Post-operative laminectomy wounds are frequently accompanied by seromas. Post-operative wound drainage may be colonized or infected. The differentiation of wound colonization from infection is difficult for non-infectious disease physicians. External chart reviewers classified 31/1531 laminectomies (over three years) as post-operative wound infections. We re-evaluated these cases using infectious disease criteria, i.e., while pathogens may be cultured from both colonized and infected wounds, only wound infections have a purulent discharge with abundant white blood cells (WBCs) on Gram stain. Colonized wounds have positive wound cultures but no/few WBCs on Gram stain. We found only 11/31 actual wound infections, the remainder were not bona fide wound infections, but were colonized seromas. Post-laminectomy colonized seromas that are culture positive for one or more organisms often mimic wound infections. In the era of public reporting of nosocomial infections, it is important that external reviewers differentiate colonization from infection to provide regulatory agencies with accurate data.

  12. Designing therapeutic cancer vaccines by mimicking viral infections.

    PubMed

    Sultan, Hussein; Fesenkova, Valentyna I; Addis, Diane; Fan, Aaron E; Kumai, Takumi; Wu, Juan; Salazar, Andres M; Celis, Esteban

    2017-02-01

    The design of efficacious and cost-effective therapeutic vaccines against cancer remains both a research priority and a challenge. For more than a decade, our laboratory has been involved in the development of synthetic peptide-based anti-cancer therapeutic vaccines. We first dedicated our efforts in the identification and validation of peptide epitopes for both CD8 and CD4 T cells from tumor-associated antigens (TAAs). Because of suboptimal immune responses and lack of therapeutic benefit of peptide vaccines containing these epitopes, we have focused our recent efforts in optimizing peptide vaccinations in mouse tumor models using numerous TAA epitopes. In this focused research review, we describe how after taking lessons from the immune system's way of dealing with acute viral infections, we have designed peptide vaccination strategies capable of generating very high numbers of therapeutically effective CD8 T cells. We also discuss some of the remaining challenges to translate these findings into the clinical setting.

  13. Mimicking the LCDM model with stealths

    NASA Astrophysics Data System (ADS)

    Campuzano, Cuauhtemoc; Cárdenas, Víctor H.; Herrera, Ramón

    2016-12-01

    We present a new cosmological model that mimics the Lambda Cold Dark Matter by using a stealth field. This kind of field is characterized as not coupling directly to gravity; however, it is connected to the underlying matter content of the universe model. As is well known, stealth fields do not back-react on the space-time; however, their mimicry skills show how this field and its self-interaction potential determines the cosmic evolution. We show the study of the simplest model that can be developed with the stealth field.

  14. Achromobacter xylosoxidans Infection Presenting as a Pulmonary Nodule Mimicking Cancer ▿

    PubMed Central

    Claassen, Stephanie L.; Reese, Jason M.; Mysliwiec, Vincent; Mahlen, Steven D.

    2011-01-01

    Achromobacter xylosoxidans is typically isolated from pulmonary sources, presenting as pneumonia in immunosuppressed individuals. We describe a novel clinical presentation of A. xylosoxidans infection presenting as multiple spiculated, pulmonary nodules mimicking cancer for which the patient underwent a wedge resection of the lung for diagnosis and staging of presumptive cancer. PMID:21593259

  15. Systemic Bacillus species infection mimicking listeriosis of pregnancy.

    PubMed

    Workowski, K A; Flaherty, J P

    1992-03-01

    Bacillus species are increasingly recognized as agents of infection in humans. These organisms are ubiquitous in nature and can cause clinical illness ranging from transient bacteremia to serious systemic infection. We describe a pregnant intravenous drug abuser with fever, constitutional symptoms, and premature labor. Her blood cultures yielded gram-positive bacilli, and her clinical course was consistent with systemic listeriosis of pregnancy. Pathological examination of the placenta revealed acute villitis, and Bacillus species grew from cultures of both placenta and blood. Through biochemical testing the isolate was identified as Bacillus pumilis. To our knowledge, this is the first reported case of premature labor induced by Bacillus species infection.

  16. Dipylidium caninum mimicking recurrent enterobius vermicularis (pinworm) infection.

    PubMed

    Samkari, Ayman; Kiska, Deanna L; Riddell, Scott W; Wilson, Kathy; Weiner, Leonard B; Domachowske, Joseph B

    2008-05-01

    Pinworm infection is a very common diagnosis in young children that is not always confirmed through laboratory evaluation before empiric therapy is prescribed. This article describes a toddler who was treated several times for pinworms because small white worms were seen in her perianal area. Laboratory analysis of parasite material found in her diaper later confirmed a diagnosis of dipylidiasis. Because the signs of dipylidiasis and pinworm infection overlap and the treatments for these parasitic infections are different, the laboratory should clinically confirm suspected persistent or recurrent pinworms.

  17. Aggregatibacter actinomycetemcomitans infection mimicking lung cancer: a case report.

    PubMed

    Matzumura-Kuan, Melissa; Jennings, Jeffrey

    2014-09-01

    Pulmonary infections can mimic a pulmonary neoplasm. Multiple organisms, including bacteria, viruses, and fungi, can present with similar clinical, radiographic, and surgical findings as neoplastic processes. Because treatment and the prognosis are completely different, an accurate diagnosis is crucial, and lung biopsy is usually required. Aggregatibacter actinomycetemcomitans is part of the normal oral flora and is a rare cause of invasive infection due to hematogenous dissemination or aspiration, particularly infective endocarditis. We present a case of A. actinomycetemcomitans and Actinomyces co-infection that presented as a mediastinal mass, with surgical findings similar to lung malignancy but with biopsy and culture showing an infectious origin. After antibiotic treatment, follow-up images showed resolution of the mass.

  18. Paragonimus westermani infection mimicking recurrent lung cancer: A case report.

    PubMed

    Itoh, Naoya; Tsukahara, Mika; Yamasaki, Hiroshi; Morishima, Yasuyuki; Sugiyama, Hiromu; Kurai, Hanako

    2016-12-01

    Herein, we report a case of Paragonimus westermani infection, which required differentiation from recurrent lung cancer. A 66-year old Japanese man with a history of lung cancer who had undergone a lobectomy was referred to our clinic for treatment of cough, sputum, dyspnea, and a right pulmonary nodule. He had previously eaten seafood he visited China. P. westermani infection was confirmed by the presence of antibody against P. westermani antigen in the patient's serum and eggs in his sputum. Eventually, molecular identification by PCR-restriction fragment length polymorphism analysis and sequencing confirmed that the patient was infected with triploid forms of P. westermani. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. 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.

  20. 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.

  1. Chronic hepatitis C virus infection mimicking rheumatoid arthritis.

    PubMed

    Tănăsescu, C; Ionescu, R A

    2003-01-01

    We present the case of a young female patient diagnosed two years ago with rheumatoid arthritis (AR) for which she is taking methotrexate (MTX), who develops cutaneous lesions highly suggestive of porphyria cutanea tarda, diagnosis confirmed by biochemical means. It is noteworthy that she was regularly taking oral contraceptives until the moment of appearance of the skin lesions. The association of those two illnesses, particularly in the case of MTX treatment can raise some problems regarding the potential direct causality relationship. This is why we tried a new diagnostic hypothesis: is chronic hepatitis C virus infection, hypothesis that we verified by means of the presence of anti-VHC and of RNA-VHC. It is well known now the association between chronic viral C infection, rheumatoid syndrome and porphyria cutanea tarda (PCT). The latter are extrahepatic manifestations of that viral infection, thus representing a major indication for antiviral treatment. Our patient received that treatment and she had a very good outcome of the skin lesions. We suggest that the differential diagnosis of any arthritis should always comprise chronic hepatitis C viral infection.

  2. Infected Aortic Aneurysm Mimicking Anti-proteinase 3-Antineutrophil Cytoplasmic Antibody-associated Vasculitis

    PubMed Central

    Hachiya, Kenta; Wakami, Kazuaki; Yoshida, Atsuhiro; Suda, Hisao; Ohte, Nobuyuki

    2016-01-01

    We herein report an unusual case of an infected descending aortic pseudoaneurysm with luminal pathognomonic oscillating vegetation with serological findings and clinical features mimicking anti-proteinase 3-antineutrophil cytoplasmic antibody-associated vasculitis. The positive blood cultures and imaging findings, including a pseudoaneurysm and vegetations in the aorta, suggested the presence of an infected aortic aneurysm. The patient was successfully treated with antibiotics and endovascular aortic repair. A precise diagnosis is crucial in order to avoid inappropriate therapy such as immunosuppressive treatment, which could result in life-threatening consequences in a patient with an infected aortic aneurysm. PMID:27904110

  3. Candida glabrata infection in gastric carcinoma patient mimicking cutaneous histoplasmosis.

    PubMed

    Gugic, Dijana; Cleary, Timothy; Vincek, Vladimir

    2008-02-28

    Candida glabrata is the second most common Candida species detected among hospitalized patients in USA. In tissue C. glabrata present as yeasts, 3-5 microns in size, which are difficult to visualize on H&E stained slides but can be detected on Grocott methenamine silver (GMS) stained slides. The presence of yeasts only, without any hyphal elements, makes C. glabrata difficult to distinguish from Histoplasma capsulatum yeasts that are of similar size. Mycology culture is the method of choice for definitive identification of C. glabrata. Rapid identification is necessary, as mortality rate due to C. glabrata infection in immunocompromised patients is particularly high. We herein report a patient with inoperable gastric carcinoma, who developed cutaneous and septic form of C. glabrata infection.

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

    PubMed

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

    2016-09-01

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

  5. An extremely unusual presentation of varicella zoster viral infection of cranial nerves mimicking Garcin syndrome.

    PubMed

    Nishioka, Kenya; Fujishima, Kenji; Kobayashi, Hirokazu; Mizuno, Yoshikuni; Okuma, Yasuyuki

    2006-12-01

    We report a patient with the varicella zoster viral (VZV) infection of multiple cranial nerves mimicking Garcin syndrome, who initially presented with Ramsay Hunt syndrome (herpes zoster oticus). A 78-year-old man showed left facial palsy with zosteric eruptions in his left auricle and dysphagia, followed by left total ophthalmoplegia. His serum anti-VZV antibody titer was elevated. Cerebrospinal fluid examination revealed pleocytosis with a slightly elevated protein level. He was treated with intravenous acyclovir and corticosteroids. His tongue weakness resolved, and then ocular movement improved. The improvement of facial palsy and swallowing difficulty was delayed. VZV infection should be considered even in patients who show unilateral multiple cranial neuropathy mimicking Garcin syndrome because it is treatable.

  6. Nematode infection of the liver mimicking metastasis of malignant melanoma.

    PubMed

    Maier, M; Tappe, D; Töpfer, C; Rosenwald, A; Gassel, H-J; Timm, S

    2006-08-01

    The differential diagnoses of a circumscribed mass of the liver are varied. Especially if a malignant tumor, capable of setting metastases to the liver, is known in a patient's medical history, there might be difficulties in differentiating the tumor's entity. CASUISTRY: We report a case of a 40-year-old male with a history of malignant melanoma in whom follow-up investigations revealed a mass in the liver. The histopathological and microbiological results, however, showed an infestation of liver tissue with nematodes. Malignant tumor cells could not be detected. Roundworm-infections of the liver can present as lesions suspicious of being malignant. Therefore, along with e.g. microhamartoma, microabscesses and hepatocellular carcinoma, infestation with nematodes should be taken into consideration.

  7. Vaccination of pigs reduces Salmonella Typhimurium numbers in a model mimicking pre-slaughter stress.

    PubMed

    Leyman, Bregje; Boyen, Filip; Verbrugghe, Elin; Parys, Alexander Van; Haesebrouck, Freddy; Pasmans, Frank

    2012-11-01

    In pigs, infection with Salmonella Typhimurium often results in the development of carriers that re-excrete the organism during periods of stress. Previous studies have shown that cortisol plays a significant role in the recrudescence of Salmonella Typhimurium and that re-excretion can be induced by injections of dexamethasone. This study evaluated whether a commercially available Salmonella Typhimurium vaccine was able to reduce Salmonella excretion in a model mimicking pre-slaughter stress. Pigs were randomly assigned to either vaccination or a control group and, 5 weeks later, were infected with Salmonella Typhimurium. Twenty-three days post infection, pigs were injected with dexamethasone to induce recrudescence and Salmonella Typhimurium numbers were determined. Salmonella loads were significantly lower in the ileum and colon and in the contents of the ileum and caecum in vaccinated pigs than in non-vaccinated pigs. In addition, significantly more Salmonella positive tonsil and colon samples were found in non-vaccinated pigs. Vaccination with an attenuated vaccine reduced but did not eliminate Salmonella Typhimurium in pigs in conditions mimicking pre-slaughter stress.

  8. 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

  9. Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

    PubMed

    Viswanathan, S; Botross, N; Rusli, B N; Riad, A

    2016-11-01

    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Development of Vibrational Culture Model Mimicking Vocal Fold Tissues.

    PubMed

    Kim, Dongjoo; Lim, Jae-Yol; Kwon, Soonjo

    2016-10-01

    The vocal folds (VFs) are connective tissues with complex matrix structures that provide the required mechanical properties for voice generation. VF injury leads to changes in tissue structure and properties, resulting in reduced voice quality. However, injury-induced biochemical changes and repair in scarred VF tissues have not been well characterized to date. To treat scarred VFs, it is essential to understand how physiological characteristics of VFs tissue change in response to external perturbation. In this study, we designed a simple vibrational culture model to mimic vibratory microenvironments observed in vivo. This model consists of a flexible culture plate, three linear actuators, a stereo splitter, and a function generator. Human vocal fold fibroblast (hVFF) monolayers were established on the flexible membrane, to which normal phonatory vibrations were delivered from linear actuators and a function generator. The hVFF monolayers were exposed to the vibrational stresses at a frequency of 205 Hz for 2, 6, and 10 h with maximum displacement of 47.1 μm, followed by a 6 h rest. We then observed the changes in cell morphology, cell viability, and gene expression related to extracellular matrix components. In our dynamic culture device mimicking normal phonatory frequencies, cell proliferation increased and expression of hyaluronic acid synthase 2 was downregulated in response to vibrational stresses. The results presented herein will be useful for evaluating cellular responses following VF injuries in the presence or absence of vibrational stresses.

  11. Actinomycosis of Cecum Associated with Entamoeba Infection Mimicking Perforated Colon Cancer

    PubMed Central

    Böler, Deniz Eren; Uras, Cihan; Göksel, Süha; Karaarslan, Mehmet

    2013-01-01

    Actinomycosis is a granulomatous disease caused by Actinomyces that mimics other intra-abdominal pathologies especially neoplasms. Correct diagnosis can be rarely established before radical surgery. On the other hand Entamoeba infection affects a considerable number of people worldwide. To our knowledge only one case has been reported to be affected by both organisms. We report a man who has been operated for a mass in the cecum mimicking a perforated colon cancer. Abdominal CT revealed a mass with features of an invading neoplasm. After radical surgery, definitive pathology revealed that the mass was due to actinomycosis associated with Entamoeba infection. The postoperative period was uneventful and the patient was on long-course antibiotherapy. It is important to consider actinomycosis especially in patients with intra-abdominal masses with unusual aggressiveness to prevent unnecessary surgery. However, surgery can be unavoidable especially in the presence of complicated disease or high index of suspicion for malignancy. PMID:23738157

  12. 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

  13. Cervical amoebiasis mimicking cervical carcinoma: A rare presentation of a common infection.

    PubMed

    Ahuja, Arvind; Bhardwaj, Minakshi

    2016-01-01

    Cervical amoebiasis is an extremely rare diagnosis with only a small number of published case reports. This disease may present as cervical growth mimicking cervical carcinoma. Owing to the similarity of the clinical presentation of bleeding per vagina and per speculum examination showing growth or ulcers, definitive diagnosis is made on microscopic examination only. We present a rare case of cervical amoebiasis in a 28-year-old, multiparous female who presented with a history of vaginal bleeding. The patient was treated with metronidazole and diloxanide furate, after which she recovered. Awareness of this rare entity is important for clinical suspicion and for the pathologist to identify trophozoites and make a diagnosis, preventing unwarranted investigations. Accurate diagnosis also facilitates quick management of a patient; as this disease is an infective pathology that can easily be treated by antibiotics. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  14. Hepatic angiosarcoma mimicking congenital cytomegalovirus infection in an infant with thrombocytopenia.

    PubMed

    Yoon, Hoi Soo; Choi, Yong-Sung; Im, Ho Joon

    2015-04-01

    Hepatic angiosarcomas are uncommon, highly aggressive tumors, rarely seen in children. A 3-month-old female infant was admitted to hospital for evaluation of multiple petechiae on her body. She had hepatosplenomegaly and scattered petechiae over her entire body. Laboratory tests indicated thrombocytopenia and positive cytomegalovirus (CMV) polymerase chain reaction. Ganciclovir was started, and the platelet count increased. After 4 months the patient was readmitted to hospital for drowsy mental status and eventually died from severe bleeding. Needle biopsy of the liver was performed after receiving written consent from the parents. Pathological findings of the liver lesion included features consistent with hepatic angiosarcoma. There have been no previous reports of hepatic angiosarcoma in Korean infants. Here, we report an infant with hepatosplenomegaly and thrombocytopenia who was diagnosed with hepatic angiosarcoma mimicking congenital CMV infection.

  15. 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

  16. Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

    PubMed

    Naselli, Aldo; Pala, Giovanna; Cresta, Federico; Finetti, Martina; Biancheri, Roberta; Renna, Salvatore

    2014-11-26

    Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

  17. Development of a mouse model mimicking key aspects of a viral asthma exacerbation.

    PubMed

    Clarke, Deborah L; Davis, Nicola H E; Majithiya, Jayesh B; Piper, Sian C; Lewis, Arthur; Sleeman, Matthew A; Corkill, Dominic J; May, Richard D

    2014-04-01

    Viral respiratory tract infections are known triggers of asthma exacerbations in both adults and children. The current standard of care, inhaled CS (corticosteroids) and LABAs (long-acting β2-adrenoceptor agonists), fails to prevent the loss of control that manifests as an exacerbation. In order to better understand the mechanisms underlying viral asthma exacerbations we established an in vivo model using the clinically relevant aeroallergen HDM (house dust mite) and the viral mimetic/TLR3 (Toll-like receptor 3) agonist poly(I:C). Poly(I:C) alone induced a similar neutrophilic inflammatory profile in the BAL (bronchoalveolar lavage) to that of HRV1b (human rhinovirus 1b) alone, accompanied by both elevated BAL KC (keratinocyte-derived chemokine) and IL-1β (interleukin-1β). When mice allergic to HDM were also challenged with poly(I:C) the neutrophilic inflammatory profile was exacerbated. Increased CD8(+) T-cell numbers, increased CD4(+) and CD8(+) cell activation and elevated KC and IL-1β were observed. No increases in Th2 cytokines or the eosinophil chemoattractant CCL11 [chemokine (C-C motif) ligand 11], above those induced by HDM alone, were observed. The poly(I:C)-exacerbated neutrophilia did not translate into changes in AHR (airways hyper-responsiveness), indicating that in this model inflammation and AHR are two mechanistically independent events. To test the clinical relevance of this model CS sensitivity was assessed using prednisone, a synthetic oral CS used to manage exacerbations in asthmatic patients already on maximal doses of inhaled CS. The increased neutrophils, and accompanying cytokines/chemokines KC and IL-1β induced by poly(I:C) challenge of HDM-sensitized and challenged mice were insensitive to oral prednisone therapy. In summary we have described a CS-resistant mouse model mimicking the key aspects of viral asthma exacerbation using the clinically relevant aeroallergen HDM and the viral mimic poly(I:C). This model may provide better

  18. Experimental assessment of four ultrasound scattering models for characterizing concentrated tissue-mimicking phantoms.

    PubMed

    Franceschini, Emilie; Guillermin, Régine

    2012-12-01

    Tissue-mimicking phantoms with high scatterer concentrations were examined using quantitative ultrasound techniques based on four scattering models: The Gaussian model (GM), the Faran model (FM), the structure factor model (SFM), and the particle model (PM). Experiments were conducted using 10- and 17.5-MHz focused transducers on tissue-mimicking phantoms with scatterer concentrations ranging from 1% to 25%. Theoretical backscatter coefficients (BSCs) were first compared with the experimentally measured BSCs in the forward problem framework. The measured BSC versus scatterer concentration relationship was predicted satisfactorily by the SFM and the PM. The FM and the PM overestimated the BSC magnitude at actual concentrations greater than 2.5% and 10%, respectively. The SFM was the model that better matched the BSC magnitude at all the scatterer concentrations tested. Second, the four scattering models were compared in the inverse problem framework to estimate the scatterer size and concentration from the experimentally measured BSCs. The FM did not predict the concentration accurately at actual concentrations greater than 12.5%. The SFM and PM need to be associated with another quantitative parameter to differentiate between low and high concentrations. In that case, the SFM predicted the concentration satisfactorily with relative errors below 38% at actual concentrations ranging from 10% to 25%.

  19. Development of a tissue-mimicking neck model for medical education.

    PubMed

    Xu, Jason J; Fung, Kevin; Glicksman, Jordan T; Brandt, Michael G; Campbell, Gordon

    2012-04-01

    The ability to palpate neck masses and lymph nodes and appreciate qualities such as size, location, and consistency is critical for patient care and an important clinical skill for all physicians. Medical students currently learn neck palpation by practicing on healthy, standardized patients; however, studies of similar procedures have shown that educational models with simulated pathology help improve technique and confidence. Our goal was to create a tissue-mimicking neck model with palpable masses. Iterative design and development of a high-fidelity neck model using polyvinyl alcohol-cryogel (PVA-C), a nontoxic and biocompatible polymer that exhibits favourable tissue-mimicking elastic properties. Model geometries were digitally reconstructed from high-resolution cadaveric magnetic resonance imaging sections to create physical moulds through stereolithography. PVA-C was formulated to mimic the characteristics of human tissue. A life-like neck model was built and consists of these components: muscle, larynx, spine, soft tissue, pathologic nodes, and skin. A final neck model prototype has been completed and will be evaluated by otolaryngology consultants and residents for face and construct validity and assessed in a randomized, controlled trial to evaluate how it impacts students' ability to detect neck masses.

  20. Herpes Simplex Virus Infection Mimicking Bullous Disease in an Immunocompromised Patient

    PubMed Central

    Lecluse, Anne L.Y.; Bruijnzeel-Koomen, Carla A.F.M.

    2010-01-01

    Immunodeficient patients are at risk of developing extended or atypical herpes simplex virus infections, which can be easily misdiagnosed. We present the case of a 79-year-old, treatment-induced (oral corticosteroid), immunocompromised female with an extensive atypical herpes simplex virus infection. This patient presented with multiple erosions and vesicles on the trunk with a subacute onset. The clinical differential diagnosis was herpes simplex infection, herpes zoster infection, pemphigus vulgaris or bullous pemphigoid. Due to the atypical clinical presentation and negative Tzanck test, suspicion of viral infection was low. High-dose steroid treatment was initiated. Subsequent histopathology, however, showed a herpes simplex virus infection. After discontinuing steroid treatment and initiating antiviral treatment, the patient recovered within a week. Emphasis must be placed on the importance of clinical awareness of extended and clinically atypical herpes simplex infections in immunocompromised patients. A negative Tzanck test does not rule out the possibility of a herpes infection. PMID:21103195

  1. Dermatophyte infections mimicking other skin diseases: a 154-person case survey of tinea atypica in the district of Cagliari (Italy).

    PubMed

    Atzori, Laura; Pau, Monica; Aste, Natalia; Aste, Nicola

    2012-04-01

    Although usually simple, the diagnosis of dermatophyte infection is sometimes neglected. An observational study has been realized to evaluate the role of corticosteroid exposure (tinea incognito) and of other primary characteristics of the dermatophytosis that from onset mimic other diseases and mislead an unexperienced physician. Between 1990 and 2009, all cases of atypical dermatophytosis mimicking other skin diseases were collected from the more general number of dermatophyte infections diagnosed at the Dermatology Department of Cagliari University, Italy. One-hundred and fifty-four cases (71 male/83 female, 2-81 years old) were studied, with a median of 7 cases/year. The most observed clinical forms were those mimicking impetigo, eczematous dermatitis, lupus erythematosus, polymorphous light eruption, psoriasis, and rosacea. The identified dermatophytes were: Microsporum canis (70 cases), Trichophyton rubrum (43 cases), Trichophyton mentagrophytes var. mentagrophytes (29 cases), Trichophyton mentagrophytes var. interdigitale (six cases), Microsporum gypseum (three cases), Epidermophyton floccosum (two cases), and Trichophyton verrucosum (one case). Diagnostic difficulties are discussed, with special attention to the origin of the pathomorphosis. In our experience, clinical atypia is not a mere consequence of corticosteroid therapy but present at the very onset of the illness, due to the variable dermatophyte invasive capacity, the site of invasion, physiological individual, and/or acquired condition, such as excessive washing or sun exposure. Therefore, we suggest using the term "tinea atypica" rather than "tinea incognito" to include all forms of dermatophytosis that do not present the classic features for both primary and secondary pathomorphosis. © 2012 The International Society of Dermatology.

  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. Neonatal cholestasis mimicking biliary atresia: Could it be urinary tract infection?

    PubMed

    Pereira, Noella Maria Delia; Shah, Ira

    2017-01-01

    Cholestasis can occur in newborns due to infections. However, the manifestations of the underlying infections usually dominate the presentation. We present a 2-month-old infant who presented with jaundice and no fever or signs of systemic illness. Liver biopsy was suggestive of cholangitis. He was subsequently detected to have urinary tract infection with Klebsiella pneumoniae. The child was treated with appropriate antibiotics for 2 weeks following which the cholestasis resolved. Thus, neonatal cholestasis due to infections can also occur in the post-neonatal period without clinical manifestations of an underlying infection.

  4. Neonatal cholestasis mimicking biliary atresia: Could it be urinary tract infection?

    PubMed Central

    Pereira, Noella Maria Delia; Shah, Ira

    2017-01-01

    Cholestasis can occur in newborns due to infections. However, the manifestations of the underlying infections usually dominate the presentation. We present a 2-month-old infant who presented with jaundice and no fever or signs of systemic illness. Liver biopsy was suggestive of cholangitis. He was subsequently detected to have urinary tract infection with Klebsiella pneumoniae. The child was treated with appropriate antibiotics for 2 weeks following which the cholestasis resolved. Thus, neonatal cholestasis due to infections can also occur in the post-neonatal period without clinical manifestations of an underlying infection. PMID:28321310

  5. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-12-18

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

  8. Infection by Mycobacterium avium intracellulare in AIDS: endoscopic duodenal appearance mimicking Whipple's disease.

    PubMed

    Vázquez-Iglesias, J L; Yañez, J; Durana, J; Arnal, F

    1988-09-01

    We report the case of a 24-year-old woman who presented with diarrhea, weight loss and abdominal lymph node enlargement. A diagnosis of infection by Mycobacterium avium intracellulare with a clinical picture similar to Whipple's disease was established. The endoscopic study of the duodenum revealed multiple yellow nodules that became confluent in the second portion, entirely replacing the normal mucosa. These endoscopic findings have not been described previously in intestinal infection by Mycobacterium avium intracellulare.

  9. Intramedullary dermoid cyst infection mimicking holocord tumor: should radical resection be mandatory?-a case report.

    PubMed

    Karaaslan, Burak; Ülkü, Göktuğ; Ucar, Murat; Demirdağ, Tuğba Bedir; İnan, Arda; Börcek, Alp Özgün

    2016-11-01

    Dermoid cysts are benign lesions which contain epidermal and dermal elements. Dermoid cysts usually contain a dermal sinus tract but this is not mandatory. Dermoid cysts can manifest by spinal cord infection without a dermal sinus tract. An infected spinal dermoid cyst associated with a holocord spinal abscess poses diagnostic and surgical challenges. Although radical surgical drainage is considered as the main treatment modality for spinal abscess, less extensive surgery for microbiological sampling and appropriate antibiotic treatment can be another alternative modality. A 1-year-old boy patient was admitted to our hospital with progressive paraplegia, bladder dysfunction, and neck rigidity. Medical history of the patient included recurrent urinary tract infection and cephalosporin treatments several times. Initial neurological examination revealed confusion, fever, neck rigidity, paraplegia (also, the motor power of the right upper extremity was three fifths that of the upper extremities). He had urinary and gastrointestinal retention. Conservative surgery was performed to take pathological and microbiological samples. With appropriate antibiotic regimen, the nuchal rigidity and fever improved dramatically. Infectious parameters in blood biochemistry significantly decreased after the antibiotic regimen. Holocord spinal abscesses are a rare entity. The source of the disease can be hemopoietic spread or contagious spread. The dermal sinus tract is major risk factor for contagious spread. The major hemopoietic sources are urogenital infection, endocarditis, and infective lung diseases. The hemopoietic spread is a more common source for pediatric patients. The thoracolumbar region is the most common site of involvement. Spinal infection has a tendency to extend longitudinally throughout spinal fibers. The pathogenesis of the holocord edema or syrinx is uncertain. The underlying etiology may be inflammation, infection, and associated venous congestion within the

  10. 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

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

    PubMed

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

    2014-01-01

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

  12. Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein-Barr virus infection.

    PubMed

    Nomura, Keiko; Kanegane, Hirokazu; Otsubo, Keisuke; Wakiguchi, Hiroshi; Noda, Yukihiro; Kasahara, Yoshihito; Miyawaki, Toshio

    2011-06-01

    Chronic active Epstein-Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.

  13. Postoperative spinal infection mimicking systemic vasculitis with titanium-spinal implants.

    PubMed

    Sakellariou, Vasileios I; Atsali, Erato; Starantzis, Konstantinos; Batistaki, Chrysanthi; Brozou, Triantafyllia; Pantos, Panayiotis; Stathopoulos, Konstantinos; Soultanis, Konstantinos

    2011-09-13

    Secondary systemic vasculitis after posterior spinal fusion surgery is rare. It is usually related to over-reaction of immune-system, to genetic factors, toxicity, infection or metal allergies. A 14 year-old girl with a history of extended posterior spinal fusion due to idiopathic scoliosis presented to our department with diffuse erythema and nephritis (macroscopic hemuresis and proteinuria) 5 months post surgery. The surgical trauma had no signs of inflammation or infection. The blood markers ESR and CRP were increased. Skin tests were positive for nickel allergy, which is a content of titanium alloy. The patient received corticosteroids systematically (hydrocortisone 10 mg) for 6 months, leading to total recess of skin and systemic reaction. However, a palpable mass close to the surgical wound raised the suspicion of a late infection. The patient had a second surgery consisting of surgical debridement and one stage revision of posterior spinal instrumentation. Intraoperative cultures were positive to Staphylococcus aureus. Intravenous antibiotics were administered. The patient is now free of symptoms 24 months post revision surgery without any signs of recurrence of either vasculitis or infection. Systemic vasculitis after spinal surgery is exceptionally rare. Causative factors are broad and sometimes controversial. In general, it is associated with allergy to metal ions. This is usually addressed with metal on metal total hip bearings. In spinal surgery, titanium implants are considered to be inert and only few reports have presented cases with systemic vasculitides. Therefore, other etiologies of immune over-reaction should always be considered, such as drug toxicity, infection, or genetic predisposition. Our purpose was to highlight the difficulties during the diagnostic work-up for systemic vasculitis and management in cases of posterior spinal surgery.

  14. 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.

  15. Mycoplasma pneumoniae infection associated with urticarial vasculitis mimicking adult-onset Still's disease.

    PubMed

    Dua, Janet; Nandagudi, Anupama; Sutcliffe, Nurhan

    2012-12-01

    Mycoplasma pneumoniae is well known to be a frequent cause of atypical pneumonia worldwide. However, it may also present with a wide variety of clinical features, including cutaneous symptoms, which are not widely recognised. Urticarial vasculitis occurring with M. pneumoniae has been described to occur in only one other case report. This amalgamation of non-specific clinical symptoms and signs can lead to a diagnostic dilemma. We describe a case of M. pneumoniae infection presenting with extrapulmonary manifestations and urticarial vasculitis, which was misdiagnosed as adult-onset Still's disease (AOSD). Had immunosuppressive therapy been commenced for AOSD in the presence of undiagnosed infection, this may have resulted in potentially serious consequences. This case highlights the need to remain vigilant about diagnosing M. pneumoniae as its serological diagnosis may take weeks and it has many extrapulmonary manifestations, which can masquerade as other conditions.

  16. 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.

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

    PubMed

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

    2015-01-01

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

  18. Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

    PubMed Central

    Ganiem, A. Rizal; Dian, Sofiati; Indriati, Agnes; Chaidir, Lidya; Wisaksana, Rudi; Sturm, Patrick; Melchers, Willem; van der Ven, Andre; Parwati, Ida; van Crevel, Reinout

    2013-01-01

    Background HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. Methodology/Principal Findings We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04–4.47) compared to those with a negative PCR. Conclusions/Significance Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available. PMID:23326616

  19. Cerebral toxoplasmosis mimicking subacute meningitis in HIV-infected patients; a cohort study from Indonesia.

    PubMed

    Ganiem, A Rizal; Dian, Sofiati; Indriati, Agnes; Chaidir, Lidya; Wisaksana, Rudi; Sturm, Patrick; Melchers, Willem; van der Ven, Andre; Parwati, Ida; van Crevel, Reinout

    2013-01-01

    HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04-4.47) compared to those with a negative PCR. Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available.

  20. A Case of Anti-Glomerular Basement Membrane Glomerulonephritis Complicated by Type 1 Diabetes Mellitus, Mimicking Urinary Tract Infection

    PubMed Central

    Aoki, Yoshihiro; Tanimoto, Izumi; Miyauchi, Yoshihiro; Suzuki, Yoshio; Shiojiri, Toshiaki

    2017-01-01

    Patient: Female, 44 Final Diagnosis: Anti-glomerular basement membrane glomerulonephritis Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Type 1 diabetes mellitus (DM) tends to complicate other autoimmune diseases. When considering renal dysfunction in patients with DM, diabetic nephropathy is a likely diagnosis. By contrast, anti-glomerular basement membrane (GBM) glomerulonephritis, an autoimmune disease, is one cause of rapidly progressive glomerulonephritis. Case Report: We report the case of a 44-year-old woman diagnosed with anti-glomerular basement membrane (GBM) glomerulonephritis. The diagnosis was made on the basis of serological test results and pathological findings of a renal biopsy. Five years before admission, she was diagnosed with type 1 DM. At admission, she presented with a fever, chills, nausea, low back pain, and malaise, which were followed by progressive renal dysfunction. The initial presentation mimicked a urinary tract infection, which delayed the correct diagnosis. Conclusions: Our patient’s course strongly suggests that rapidly progressive glomerulonephritis should be considered as an early differential diagnosis in cases of progressive renal dysfunction, especially when accompanied by fever, regardless of the underlying disease. PMID:28344312

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

    PubMed

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

    2016-04-02

    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.

  2. 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.

  3. 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

  4. Infected lumbar dermoid cyst mimicking intramedullary spinal cord tumor: Observations and outcomes

    PubMed Central

    Vadivelu, Sudhakar; Desai, Sohum K.; Illner, Anna; Luerssen, Thomas G.; Jea, Andrew

    2014-01-01

    We report two unusual cases of a 17-month-old boy with a previously undiagnosed lumbar dermal sinus tract terminating in an intradural dermoid cyst and holocord edema or syrinx, presenting with paraparesis and sphincter dysfunction secondary to an intramedullary abscess and a 26-month-old boy with a previously undiagnosed lumbar dermal sinus tract terminating in an infected dermoid cyst and intramedullary abscess, presenting with recurrent episodes of meningitis and hydrocephalus. Pre-operative magnetic resonance imaging (MRI) studies in these patients were initially confused for an intramedullary spinal cord tumor; however, the presence of an associated dermal sinus tract made this diagnosis of neoplasm less likely. Total excision of the dermal sinus tract, debulking of the dermoid cyst and drainage of the intramedullary abscess through an L1-L5 osteoplastic laminoplasty and midline myelotomy, followed by long-term antibiotic therapy resulted in a good functional recovery. Post-operative MRI of the spine showed removal of the dermoid cyst, decreased inflammatory granulation tissue and resolution of the holocord edema or syrinx. We also performed a literature review to determine the cumulative experience of management of intramedullary abscess in this rare clinical setting. PMID:24891897

  5. 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.

  6. 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.

  7. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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.

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

    PubMed

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

    2015-03-15

    Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

  10. 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.

  11. [Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

    PubMed

    Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

    2008-10-14

    To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

  12. A new murine model of sustainable and durable chronic critical limb ischemia fairly mimicking human pathology.

    PubMed

    Lejay, A; Choquet, P; Thaveau, F; Singh, F; Schlagowski, A; Charles, A-L; Laverny, G; Metzger, D; Zoll, J; Chakfe, N; Geny, B

    2015-02-01

    To establish a chronic mouse model of critical limb ischemia (CLI) with in vivo and ex vivo validation, closely mimicking human pathology. Swiss mice (n = 28) were submitted to sequential unilateral femoral (day 0) and iliac (day 4) ligatures. Ischemia was confirmed by clinical scores (tissue and functional damages) and methoxyisobutylisonitrile (MIBI) scintigraphies at days 0, 4, 6, 10, 20, and 30. At days 10, 20, and 30, muscle mitochondrial respiration, calcium retention capacity (CRC), and production of reactive oxygen species (ROS) were investigated, together with transcripts of mitochondrial biogenesis and antioxidant enzymes. Histological analysis was also performed. Clinical and functional damage confirmed CLI. MIBI scintigraphies showed hypoperfusion of the ischemic limb, which remained stable until day 30. Mitochondrial respiration was impaired in ischemic muscles compared with controls (Vmax = 7.93 ± 0.99 vs. 10.09 ± 2.87 mmol/L O2/minute/mg dry weight [dw]; p = .01), together with impaired CRC (7.4 ± 1.6 mmol/L minute/mg dw vs. 11.9 ± 0.9 mmol/L minute/mg dw; p < .001) and biogenesis (41% decrease in peroxisome proliferator-activated receptor gamma coactivator [PGC]-1α, 49% decrease in PGC-1β, and 41% decrease in nuclear respiratory factor-1). Ischemic muscles also demonstrated increased production of ROS under electron paramagnetic resonance (0.084 ± 0.029 vs. 0.051 ± 0.031 mmol/L minute/mg dw; p = .03) and with dihydroethidium staining (3622 ± 604 arbitrary units of fluorescence vs. 1224 ± 324; p < .01), decreased antioxidant enzymes (32% decrease in superoxide dismutase [SOD]1, 41% decrease in SOD2, and 49% decrease in catalase), and myopathic features (wider range in fiber size, rounded shape, centrally located nuclei, and smaller cross-sectional areas). All defects were stable over time. Sequential femoral and iliac ligatures closely mimic human functional, clinical, scintigraphic, and skeletal muscle

  13. Image-based 3D modeling and validation of radiofrequency interstitial tumor ablation using a tissue-mimicking breast phantom.

    PubMed

    Wang, Zhigang; Aarya, Isshaa; Gueorguieva, Mariana; Liu, Dun; Luo, Hongyan; Manfredi, Luigi; Wang, Lijun; McLean, Donald; Coleman, Stuart; Brown, Stuart; Cuschieri, Alfred

    2012-11-01

    Minimally invasive treatment of solid cancers, especially in the breast and liver, remains clinically challenging, despite a variety of treatment modalities, including radiofrequency ablation (RFA), microwave ablation or high-intensity focused ultrasound. Each treatment modality has advantages and disadvantages, but all are limited by placement of a probe or US beam in the target tissue for tumor ablation and monitoring. The placement is difficult when the tumor is surrounded by large blood vessels or organs. Patient-specific image-based 3D modeling for thermal ablation simulation was developed to optimize treatment protocols that improve treatment efficacy. A tissue-mimicking breast gel phantom was used to develop an image-based 3D computer-aided design (CAD) model for the evaluation of a planned RF ablation. First, the tissue-mimicking gel was cast in a breast mold to create a 3D breast phantom, which contained a simulated solid tumor. Second, the phantom was imaged in a medical MRI scanner using a standard breast imaging MR sequence. Third, the MR images were converted into a 3D CAD model using commercial software (ScanIP, Simpleware), which was input into another commercial package (COMSOL Multiphysics) for RFA simulation and treatment planning using a finite element method (FEM). For validation of the model, the breast phantom was experimentally ablated using a commercial (RITA) RFA electrode and a bipolar needle with an electrosurgical generator (DRE ASG-300). The RFA results obtained by pre-treatment simulation were compared with actual experimental ablation. A 3D CAD model, created from MR images of the complex breast phantom, was successfully integrated with an RFA electrode to perform FEM ablation simulation. The ablation volumes achieved both in the FEM simulation and the experimental test were equivalent, indicating that patient-specific models can be implemented for pre-treatment planning of solid tumor ablation. A tissue-mimicking breast gel phantom

  14. 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.

  15. 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.

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

    PubMed

    Kazama, Itsuro

    2016-02-01

    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.

  17. Urticaria mimickers in children.

    PubMed

    Mathur, Anubhav N; Mathes, Erin F

    2013-01-01

    Acute urticaria is a self-limited cutaneous condition marked by transient, erythematous, and pruritic wheals. It is a hypersensitivity response that is often secondary to infection, medications, or food allergies in children. In contrast, the urticarial "mimickers" described in this review article are often seen in the context of fever and extracutaneous manifestations in pediatric patients. The differential diagnosis ranges from benign and self-limited hypersensitivity responses to multisystem inflammatory diseases. Establishing the correct diagnosis of an urticarial rash in a pediatric patient is necessary to both prevent an unnecessary work up for self-limited conditions and to appropriately recognize and evaluate multisystem inflammatory disorders. Herein, we describe two cases to illustrate the clinical manifestations, laboratory findings, histopathology and differential diagnoses for several mimickers of acute urticaria including: urticaria multiforme, serum sickness like reaction, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, systemic onset juvenile idiopathic arthritis, cryopyrin associated periodic syndromes, and urticarial vasculitis. © 2013 Wiley Periodicals, Inc.

  18. 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.

  19. A new model of retinal photoreceptor cell degeneration induced by a chemical hypoxia-mimicking agent, cobalt chloride.

    PubMed

    Hara, Akira; Niwa, Masayuki; Aoki, Hitomi; Kumada, Masako; Kunisada, Takahiro; Oyama, Takeru; Yamamoto, Tetsuya; Kozawa, Osamu; Mori, Hideki

    2006-09-13

    Retinal photoreceptor cell degeneration was induced by cobalt chloride, a chemical hypoxia-mimicking agent in rodents. Time course and dose-response of photoreceptor cell degeneration in mouse retina after intravitreal injection of cobalt chloride were examined by conventional histological analysis by hematoxylin and eosin staining and in situ terminal dUTP-biotin nick end labeling of DNA fragments (TUNEL) method with the use of paraffin-embedded sections. The dose-response of photoreceptor cell degeneration in rat retina was also examined. Photoreceptor cells progressively degenerated with time and under dose-response relationship. The suitable dose of cobalt chloride for the selective photoreceptor cell degeneration in mice is 10-12 nmol intravitreal injection at the volume of 2 microl. The retinal morphology of the mice 2 weeks after the 10-12 nmol intravitreal injection was similar to that of retinal degeneration in the mutant rd mouse. Retinal damage of total retinal layers was induced by an excessive dose of cobalt chloride. The progression of retinal damage after cobalt chloride injection, measured morphologically, was completed at 1 week. However, nuclear DNA fragmentation, mainly detected at outer nuclear layer by TUNEL, peaked at 48 h after 12 nmol cobalt chloride injection. Thus, the selective photoreceptor cell degeneration induced by cobalt chloride follows DNA fragmentation at outer nuclear layer. The photoreceptor cell degeneration is established optionally by cobalt chloride without use of the retinal degeneration mutant animals. Thus, we have described the development of a new model of retinal photoreceptor cell degeneration induced by a chemical hypoxia-mimicking agent.

  20. 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

  1. Mimicking the intramolecular hydrogen bond: synthesis, biological evaluation, and molecular modeling of benzoxazines and quinazolines as potential antimalarial agents.

    PubMed

    Gemma, Sandra; Camodeca, Caterina; Brindisi, Margherita; Brogi, Simone; Kukreja, Gagan; Kunjir, Sanil; Gabellieri, Emanuele; Lucantoni, Leonardo; Habluetzel, Annette; Taramelli, Donatella; Basilico, Nicoletta; Gualdani, Roberta; Tadini-Buoninsegni, Francesco; Bartolommei, Gianluca; Moncelli, Maria Rosa; Martin, Rowena E; Summers, Robert L; Lamponi, Stefania; Savini, Luisa; Fiorini, Isabella; Valoti, Massimo; Novellino, Ettore; Campiani, Giuseppe; Butini, Stefania

    2012-12-13

    The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum ) and in vivo (against Plasmodium berghei ). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei -infected mice.

  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. Biofilm models of polymicrobial infection

    PubMed Central

    Gabrilska, Rebecca A; Rumbaugh, Kendra P

    2015-01-01

    Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed. PMID:26592098

  4. RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.

    PubMed

    Ulrick, Nicole; Goldstein, Amy; Simons, Cas; Taft, Ryan J; Helman, Guy; Pizzino, Amy; Bloom, Miriam; Vogt, Julie; Pysden, Karen; Diodato, Daria; Martinelli, Diego; Monavari, Ahmad; Buhas, Daniela; van Karnebeek, Clara D M; Dorboz, Imen; Boespflug-Tanguy, Odile; Rodriguez, Diana; Tétreault, Martine; Majewski, Jacek; Bernard, Genevieve; Ng, Yi Shiau; McFarland, Robert; Vanderver, Adeline

    2017-01-01

    Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection. We reviewed a large-scale biorepository of patients with unsolved leukodystrophies and identified two individuals with required for meiotic nuclear division 1 (RMND1) mutations and similar magnetic resonance imaging (MRI) features, including temporal lobe cysts. Ten additional subjects with confirmed RMND1 mutations were identified as part of a separate disease specific cohort. Brain MRIs from all 12 individuals were reviewed for common neuroradiological features. MRI features in RMND1 mutations included temporal lobe swelling, with rarefaction and cystic evolution, enlarged tips of the temporal lobes, and multifocal subcortical white matter changes with confluent periatrial T2 signal hyperintensity. A combination of these features was present in ten of the 12 individuals reviewed. Despite the small number of reported individuals with RMND1 mutations, a clinically recognizable phenotype of leukoencephalopathy with temporal lobe swelling, rarefaction, and cystic changes has emerged in a subset of individuals. Careful clinical phenotyping, including for lactic acidosis, deafness, and severe muscle involvement seen in RMND1 mutation positive individuals, and MRI pattern recognition will be important in differentiating these patients from children with congenital infections like cytomegalovirus. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  6. RITONAVIR-ASSOCIATED TOXICITY MIMICKING RETINITIS PIGMENTOSA IN AN HIV-INFECTED PATIENT ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY.

    PubMed

    Papavasileiou, Evangelia; Younis, Saad; Zygoura, Vasiliki; Quijano, Claudia; Jackson, Timothy L

    2017-01-01

    To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy-associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

  7. Identification of Entry Factors Involved in Hepatitis C Virus Infection Based on Host-Mimicking Short Linear Motifs

    PubMed Central

    2017-01-01

    Host factors that facilitate viral entry into cells can, in principle, be identified from a virus-host protein interaction network, but for most viruses information for such a network is limited. To help fill this void, we developed a bioinformatics approach and applied it to hepatitis C virus (HCV) infection, which is a current concern for global health. Using this approach, we identified short linear sequence motifs, conserved in the envelope proteins of HCV (E1/E2), that potentially can bind human proteins present on the surface of hepatocytes so as to construct an HCV (envelope)-host protein interaction network. Gene Ontology functional and KEGG pathway analyses showed that the identified host proteins are enriched in cell entry and carcinogenesis functionalities. The validity of our results is supported by much published experimental data. Our general approach should be useful when developing antiviral agents, particularly those that target virus-host interactions. PMID:28129350

  8. Enterobius vermicularis (pinworm) infection of the liver mimicking malignancy: Presentation of a new case and review of current literature.

    PubMed

    Arkoulis, Nikolaos; Zerbinis, Helen; Simatos, Georgios; Nisiotis, Athanasios

    2012-01-01

    Enterobius vermicularis or "pinworm" infection of the liver is an extremely rare condition with only five cases previously reported in literature. It is characterized by the presence of granulomas in the liver with a necrotic core, containing adult helminthes or their ova. Because of the relatively mild symptomatology associated with this disease, prior to the arrival of modern imaging methods hepatic enterobiasis was an incidental intra-operative finding during abdominal surgery for other conditions. In recent years however, with high-resolution abdominal imaging readily available and the improved safety of hepatic resection, a lower threshold for treating suspicious hepatic nodules aggressively with surgery is being adopted. We present the second case in international literature, where E. vermicularis of the liver was mistaken for malignancy and led to hepatic resection and perform a literature review of the five previously documented cases of hepatic enterobiasis. Our report identifies certain trends in this condition's aetiology and clinical behaviour, but due to its rarity definitive answers cannot yet be established. We do not advocate a change in the current approach of suspicious hepatic nodules, but we do feel that better understanding of the mechanisms involved with hepatic enterobiasis could, in the future, prevent unnecessary surgery.

  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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-07-01

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

  11. Invertebrate models of fungal infection.

    PubMed

    Arvanitis, Marios; Glavis-Bloom, Justin; Mylonakis, Eleftherios

    2013-09-01

    The morbidity, mortality and economic burden associated with fungal infections, together with the emergence of fungal strains resistant to current antimicrobial agents, necessitate broadening our understanding of fungal pathogenesis and discovering new agents to treat these infections. Using invertebrate hosts, especially the nematode Caenorhabditis elegans and the model insects Drosophila melanogaster and Galleria mellonella, could help achieve these goals. The evolutionary conservation of several aspects of the innate immune response between invertebrates and mammals makes the use of these simple hosts an effective and fast screening method for identifying fungal virulence factors and testing potential antifungal compounds. The purpose of this review is to compare several model hosts that have been used in experimental mycology to-date and to describe their different characteristics and contribution to the study of fungal virulence and the detection of compounds with antifungal properties. This article is part of a Special Issue entitled: Animal Models of Disease.

  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. 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

  15. Mimicking Tumors: Toward More Predictive In Vitro Models for Peptide- and Protein-Conjugated Drugs.

    PubMed

    van den Brand, Dirk; Massuger, Leon F; Brock, Roland; Verdurmen, Wouter P R

    2017-03-15

    Macromolecular drug candidates and nanoparticles are typically tested in 2D cancer cell culture models, which are often directly followed by in vivo animal studies. The majority of these drug candidates, however, fail in vivo. In contrast to classical small-molecule drugs, multiple barriers exist for these larger molecules that two-dimensional approaches do not recapitulate. In order to provide better mechanistic insights into the parameters controlling success and failure and due to changing ethical perspectives on animal studies, there is a growing need for in vitro models with higher physiological relevance. This need is reflected by an increased interest in 3D tumor models, which during the past decade have evolved from relatively simple tumor cell aggregates to more complex models that incorporate additional tumor characteristics as well as patient-derived material. This review will address tissue culture models that implement critical features of the physiological tumor context such as 3D structure, extracellular matrix, interstitial flow, vascular extravasation, and the use of patient material. We will focus on specific examples, relating to peptide-and protein-conjugated drugs and other nanoparticles, and discuss the added value and limitations of the respective approaches.

  16. Mimicking Tumors: Toward More Predictive In Vitro Models for Peptide- and Protein-Conjugated Drugs

    PubMed Central

    2017-01-01

    Macromolecular drug candidates and nanoparticles are typically tested in 2D cancer cell culture models, which are often directly followed by in vivo animal studies. The majority of these drug candidates, however, fail in vivo. In contrast to classical small-molecule drugs, multiple barriers exist for these larger molecules that two-dimensional approaches do not recapitulate. In order to provide better mechanistic insights into the parameters controlling success and failure and due to changing ethical perspectives on animal studies, there is a growing need for in vitro models with higher physiological relevance. This need is reflected by an increased interest in 3D tumor models, which during the past decade have evolved from relatively simple tumor cell aggregates to more complex models that incorporate additional tumor characteristics as well as patient-derived material. This review will address tissue culture models that implement critical features of the physiological tumor context such as 3D structure, extracellular matrix, interstitial flow, vascular extravasation, and the use of patient material. We will focus on specific examples, relating to peptide-and protein-conjugated drugs and other nanoparticles, and discuss the added value and limitations of the respective approaches. PMID:28122451

  17. Transgenic mouse model of IgM(+) lymphoproliferative disease mimicking Waldenström macroglobulinemia.

    PubMed

    Tompkins, V S; Sompallae, R; Rosean, T R; Walsh, S; Acevedo, M; Kovalchuk, A L; Han, S-S; Jing, X; Holman, C; Rehg, J E; Herms, S; Sunderland, J S; Morse, H C; Janz, S

    2016-11-04

    Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M(+) (IgM(+)) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EμSV-BCL2-22 and H2-L(d)-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2(+)IL6(+)AID(-) and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM(+) lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2(+)IL6(+)AID(-) model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.

  18. Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia

    PubMed Central

    Tompkins, V S; Sompallae, R; Rosean, T R; Walsh, S; Acevedo, M; Kovalchuk, A L; Han, S-S; Jing, X; Holman, C; Rehg, J E; Herms, S; Sunderland, J S; Morse, H C; Janz, S

    2016-01-01

    Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM+) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EμSV-BCL2-22 and H2-Ld-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2+IL6+AID− and found that they developed—with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)—a severe IgM+ lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2+IL6+AID− model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM. PMID:27813533

  19. Mimicking and Understanding the Agglutination Effect of the Antimicrobial Peptide Thanatin Using Model Phospholipid Vesicles.

    PubMed

    Robert, Émile; Lefèvre, Thierry; Fillion, Matthieu; Martial, Benjamin; Dionne, Justine; Auger, Michèle

    2015-06-30

    Thanatin is a cationic 21-residue antimicrobial and antifongical peptide found in the spined soldier bug Podisus maculiventris. It is believed that it does not permeabilize membranes but rather induces the agglutination of bacteria and inhibits cellular respiration. To clarify its mode of action, lipid vesicle organization and aggregation propensity as well as peptide secondary structure have been studied using different membrane models. Dynamic light scattering and turbidimetry results show that specific mixtures of negatively charged and zwitterionic phospholipid vesicles are able to mimic the agglutination effect of thanatin observed on Gram-negative and Gram-positive bacterial cells, while monoconstituent ("conventional") models cannot reproduce this phenomenon. The model of eukaryotic cell reveals no particular interaction with thanatin, which is consistent with the literature. Infrared spectroscopy shows that under the conditions under which vesicle agglutination occurs, thanatin exhibits a particular spectral pattern in the amide I' region and in the region associated with Arg side chains. The data suggest that thanatin mainly retains its hairpin structure, Arg residues being involved in strong interactions with anionic groups of phospholipids. In the absence of vesicle agglutination, the peptide conformation and Arg side-chain environment are similar to those observed in solution. The data show that a negatively charged membrane is required for thanatin to be active, but this condition is insufficient. The activity of thanatin seems to be modulated by the charge surface density of membranes and thanatin concentration.

  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. 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.

  2. Interaction of a synthetic antimicrobial peptide with a model bilayer platform mimicking bacterial membranes.

    PubMed

    Niu, Lifang; Wohland, Thorsten; Knoll, Wolfgang; Köper, Ingo

    2017-08-31

    Tethered bimolecular lipid membranes are solid supported membrane systems, which provide a versatile model platform for the study of many membrane related processes. Here, such an architecture has been used to study the interaction of the small synthetic antimicrobial peptide, V4, with membranes of various mixed lipid compositions, including membranes containing bacterial lipids. By investigating the binding of the peptide using a range of surface analytical techniques such as surface plasmon resonance and surface plasmon field-enhanced fluorescence spectroscopy as well as electrochemical impedance spectroscopy, a clear preference of the peptide for negatively charged membranes over zwitterionic ones has been shown. Additionally, the interactions seemed to indicate a cooperative behavior for the peptide binding to a membrane.

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

    PubMed Central

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

    2014-01-01

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

  4. Involvement of innate and adaptive immunity in a murine model of coronary arteritis mimicking Kawasaki disease.

    PubMed

    Schulte, Danica J; Yilmaz, Atilla; Shimada, Kenichi; Fishbein, Michael C; Lowe, Emily L; Chen, Shuang; Wong, Michelle; Doherty, Terence M; Lehman, Thomas; Crother, Timothy R; Sorrentino, Rosalinda; Arditi, Moshe

    2009-10-15

    Kawasaki disease (KD) is the most common cause of acquired cardiac disease and acute vasculitis in children in the developed world. Injection of a cell wall extract isolated from Lactobacillus casei (LCCWE) into mice causes a focal coronary arteritis that histopathologically mimics the coronary lesions observed in KD patients. In this study we used this model to investigate the participation of T cells, B cells, and dendritic cells (DC) in the development of coronary arteritis. RAG1(-/-), B cell(null), and wild-type (WT) mice were injected with a single dose of LCCWE (500 microg/mouse i.p.). None of the RAG1(-/-) mice developed coronary arteritis, whereas 70% of WT and 100% of B cell(null) mice developed coronary lesions, indicating that T cells were required for lesion formation. When splenocytes isolated from LCCWE-treated mice were restimulated with LCCWE, we observed significant IFN-gamma secretion in WT but not in RAG1(-/-) mice. Immunohistochemical staining showed F4/80(+) macrophages, activated MIDC-8(+) myeloid DCs (mDC), plasmacytoid DCs, and colocalization of CD3(+) T cells with mDCs in coronary artery lesions, suggesting an Ag-driven process. T cells but not B cells are required for LCCWE-induced coronary arteritis. Similar to human lesions, the coronary lesions contain macrophages, activated mDCs, and plaslmacytoid DCs all in close proximity to T cells, further strengthening the relevance of this mouse model to the immunopathology of coronary disease in KD. These studies are consistent with the interpretation that macrophages and DCs may collaborate with T cells in the pathological mechanisms of coronary arteritis.

  5. Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation.

    PubMed

    Desai, Chirag S; Khan, Khalid M; Ma, Xiaobo; Li, Henghong; Wang, Juan; Fan, Lijuan; Chen, Guoling; Smith, Jill P; Cui, Wanxing

    2017-09-13

    The inflammatory milieu in the liver as determined by histopathology is different in individual patients undergoing autologous islet cell transplantation. We hypothesized that inflammation related to fatty-liver adversely impacts islet survival. To test this hypothesis, we used a mouse model of fatty-liver to determine the outcome of syngeneic islet transplantation after chemical pancreatectomy. Mice (C57BL/6) were fed a high-fat-diet from 6 weeks of age until attaining a weight of ≥28 grams (6-8 weeks) to produce a fatty liver (histologically > 30% fat);steatosis was confirmed with lipidomic profile of liver tissue. Islets were infused via the intra-portal route in fatty-liver and control mice after streptozotocin induction of diabetes. Outcomes were assessed by the rate of euglycemia, liver histopathology, evaluation of liver inflammation by measuring tissue cytokines IL-1β and TNF-α by RT-PCR and CD31 expression by immunohistochemistry. The difference in the euglycemic fraction between the normal liver group (90%, 9/10) and the fatty-liver group (37.5%, 3/8) was statistically significant at the 18(th) day post- transplant and was maintained to the end of the study (day 28) (p = 0.019, X(2) = 5.51). Levels of TNF-α and IL-1β were elevated in fatty-liver mice (p = 0.042, p = 0.037). Compared to controls cytokine levels were elevated after islet cell transplantation and in transplanted fatty-liver mice as compared to either fatty- or islet transplant group alone (p = NS). A difference in the histochemical pattern of CD31 could not be determined. Fatty-liver creates an inflammatory state which adversely affects the outcome of autologous islet cell transplantation.

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

    PubMed

    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.

  7. 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

  8. A stochastic model for head lice infections.

    PubMed

    Stone, Patricia; Wilkinson-Herbots, Hilde; Isham, Valerie

    2008-06-01

    We investigate the dynamics of head lice infections in schools, by considering a model for endemic infection based on a stochastic SIS (susceptible-infected-susceptible) epidemic model, with the addition of an external source of infection. We deduce a range of properties of our model, including the length of a single outbreak of infection. We use the stationary distribution of the number of infected individuals, in conjunction with data from a recent study carried out in Welsh schools on the prevalence of head lice infections, and employ maximum likelihood methods to obtain estimates of the model parameters. A complication is that, for each school, only a sample of the pupils was checked for infection. Our likelihood function takes account of the missing data by incorporating a hypergeometric sampling element. We arrive at estimates of the ratios of the "within school" and "external source" transmission rates to the recovery rate and use these to obtain estimates for various quantities of interest.

  9. Susceptible-infected-recovered model with recurrent infection

    NASA Astrophysics Data System (ADS)

    Ruziska, Flávia M.; Tomé, Tânia; de Oliveira, Mário J.

    2017-02-01

    We analyze a stochastic lattice model describing the spreading of a disease among a community composed by susceptible, infected and removed individuals. A susceptible individual becomes infected catalytically. An infected individual may, spontaneously, either become recovered, that is, acquire a permanent immunization, or become again susceptible. The critical properties including the phase diagram is obtained by means of mean-field theories as well as numerical simulations. The model is found to belong to the universality class of dynamic percolation except when the recovering rate vanishes in which case the model belongs to the directed percolation universality class.

  10. Poly(alkylene phosphates): from synthetic models of biomacromolecules and biomembranes toward polymer-inorganic hybrids (mimicking biomineralization).

    PubMed

    Penczek, Stanislaw; Pretula, Julia; Kaluzynski, Krzysztof

    2005-01-01

    Syntheses of poly(alkylene phosphates), with repeating units having two or three methylene groups and phosphoryl groups and mimicking backbones of biomacromolecules, are reviewed. Two major methods elaborated in this laboratory, namely, ring-opening polymerization and transesterification, are described. The resulting polymers were used as carriers of cations (Ca2+ and Mg2+) in membrane processes and in controlling the crystallization of CaCO3, in a process related to biomineralization.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Adult Zebrafish model of streptococcal infection

    PubMed Central

    Phelps, Hilary A.; Runft, Donna L.

    2009-01-01

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

  17. Mouse models for filovirus infections.

    PubMed

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

    2012-09-01

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

  18. Mouse Models for Filovirus Infections

    PubMed Central

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

    2012-01-01

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

  19. A murine model of early Pseudomonas aeruginosa lung disease with transition to chronic infection

    PubMed Central

    Bayes, H. K.; Ritchie, N.; Irvine, S.; Evans, T. J.

    2016-01-01

    Pseudomonas aeruginosa (PA) remains an important pathogen in patients with cystic fibrosis (CF) lung disease as well as non-CF bronchiectasis and chronic obstructive airways disease. Initial infections are cleared but chronic infection with mucoid strains ensues in the majority of CF patients and specific interventions to prevent this critical infection transition are lacking. The PA bead model has been widely used to study pulmonary P.aeruginosa infection but has limitations in animal husbandry and in accurately mimicking human disease. We have developed an adapted agar bead murine model using a clinical mucoid strain that demonstrates the key features of transition from transitory to chronic airways infection. Infected animals show very limited acute morbidity and mortality, but undergo infection-related weight loss and neutrophilic inflammation, development of anti-pseudomonal antibodies, variable bacterial clearance, endobronchial infection and microbial adaptation with PA small colony variants. We anticipate this model will allow research into the host and microbial factors governing this critical period in Pseudomonas aeruginosa pulmonary pathogenesis when transition to chronicity is occurring. PMID:27804985

  20. Animal models of external traumatic wound infections

    PubMed Central

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

    2011-01-01

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

  1. The role of ultraviolet colour in the assessment of mimetic accuracy between Batesian mimics and their models: a case study using ant-mimicking spiders

    NASA Astrophysics Data System (ADS)

    Corcobado, Guadalupe; Herberstein, Marie E.; Pekár, Stano

    2016-12-01

    The use of ultraviolet (UV) cues for intra- and inter-specific communication is common in many animal species. Still, the role of UV signals under some predator-prey contexts, such as Batesian mimicry, is not clear. Batesian mimicry is a defensive strategy by which a palatable species (the mimic) resembles an unpalatable or noxious species (the model) to avoid predation. This strategy has evolved independently in many different taxa that are predated by species capable of UV perception. Moreover, there is considerable variation in how accurately Batesian mimics resemble their models across species. Our aim was to investigate how UV colour contributed to mimetic accuracy using several ant-mimicking spider species as a case study. We measured the reflectance spectrum (300-700 nm) for several species of mimics and models, and we tested whether they differ in visible and UV colour. We modelled whether two different predators could discriminate between mimics and models using colour information. We found that generally, ant-mimicking spiders differed significantly from their ant models in UV colour and that information from the visible range of light cannot be extrapolated into the UV. Our modelling suggested that wasps should be able to discriminate between mimics and models combining information from visible and the UV light, whereas birds may not discriminate between them. Thus, we show that UV colour can influence mimic accuracy and we discuss its potential role in Batesian mimicry. We conclude that colour, especially in the UV range, should be taken into account when measuring mimetic accuracy.

  2. The role of ultraviolet colour in the assessment of mimetic accuracy between Batesian mimics and their models: a case study using ant-mimicking spiders.

    PubMed

    Corcobado, Guadalupe; Herberstein, Marie E; Pekár, Stano

    2016-12-01

    The use of ultraviolet (UV) cues for intra- and inter-specific communication is common in many animal species. Still, the role of UV signals under some predator-prey contexts, such as Batesian mimicry, is not clear. Batesian mimicry is a defensive strategy by which a palatable species (the mimic) resembles an unpalatable or noxious species (the model) to avoid predation. This strategy has evolved independently in many different taxa that are predated by species capable of UV perception. Moreover, there is considerable variation in how accurately Batesian mimics resemble their models across species. Our aim was to investigate how UV colour contributed to mimetic accuracy using several ant-mimicking spider species as a case study. We measured the reflectance spectrum (300-700 nm) for several species of mimics and models, and we tested whether they differ in visible and UV colour. We modelled whether two different predators could discriminate between mimics and models using colour information. We found that generally, ant-mimicking spiders differed significantly from their ant models in UV colour and that information from the visible range of light cannot be extrapolated into the UV. Our modelling suggested that wasps should be able to discriminate between mimics and models combining information from visible and the UV light, whereas birds may not discriminate between them. Thus, we show that UV colour can influence mimic accuracy and we discuss its potential role in Batesian mimicry. We conclude that colour, especially in the UV range, should be taken into account when measuring mimetic accuracy.

  3. Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection

    PubMed Central

    Matsuno, Keita; Orba, Yasuko; Maede-White, Kimberly; Scott, Dana; Feldmann, Friederike; Liang, Mifang; Ebihara, Hideki

    2017-01-01

    The pathogenesis of clinical manifestations caused by newly emerging tick-borne phleboviruses [i.e., Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV)], such as severe thrombocytopenia and lymphocytopenia, are not yet fully understood. In the present study, to establish an animal model mimicking the profile of fatal human cases, we examined the susceptibilities of adult mice from 12 strains, aged mice from two strains, and cynomolgus macaques to SFTSV and/or HRTV infections. However, none of these immunocompetent animals developed lethal diseases after infection with SFTSV or HRTV. Thus, we tested a lethal animal model of SFTSV infection using interferon-α/β receptor knock-out (IFNAR-/-) mice to identify the target cell(s) of virus infection, as well as lesions that are potentially associated with hematological changes. IbaI-positive macrophages and Pax5-positive immature B cells overlapped with SFTSV-positive cells in the spleen and lymph nodes of IFNAR-/- mice, and IbaI-SFTSV-double positive cells were also observed in the liver and kidney, thereby suggesting crucial roles for macrophages in the pathogenesis of SFTSV infection in mice. In the mandibular lymph nodes and spleens of infected mice, we observed extensive necrosis comprising B220-positive B cells, which may be associated with severe lymphocytopenia. The results of this study suggest a resemblance between the IFNAR-/- mouse model and lethal infections in humans, as well as roles for multiple cells during pathogenesis in mice. PMID:28194148

  4. 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.

  5. Melorheostosis mimicking synovial osteochondromatosis.

    PubMed

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

    2014-01-01

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

  6. Mouse model of Staphylococcus aureus skin infection.

    PubMed

    Malachowa, Natalia; Kobayashi, Scott D; Braughton, Kevin R; DeLeo, Frank R

    2013-01-01

    Bacterial skin and soft tissue infections are abundant worldwide and many are caused by Staphylococcus aureus. Indeed, S. aureus is the leading cause of skin and soft tissue infections in the USA. Here, we describe a mouse model of skin and soft tissue infection induced by subcutaneous inoculation of S. aureus. This animal model can be used to investigate a number of factors related to the pathogenesis of skin and soft tissue infections, including strain virulence and the contribution of specific bacterial molecules to disease, and it can be employed to test the potential effectiveness of antibiotic therapies or vaccine candidates.

  7. [Laboratory animal infection in modeling intestinal schistosomiasis].

    PubMed

    Zelia, O P

    1984-01-01

    A comparative efficiency of different regimes for infecting laboratory animals has been determined in order to find out optimal conditions under which an experimental model of intestinal schistosomiasis (infection with Schistosoma mansoni) can be maintained. When evaluating the results of laboratory definitive hosts infection we took into account the character of Schistosoma distribution in animals, which with high probability rate was modelled by means of negative binomial distribution. The main parameters of this distribution were used for determination of effective doses and methods of animals infection alongside with generally accepted indices of infection rate and intensiveness. Analysis of the data obtained has shown that the infection of 150 cercarians per mouse and 200 cercarians per golden and striped hairy-footed hamster by their subcutaneous administration creates optimal density of parasites in the host. Results of investigations have shown that striped hairy-footed hamsters can be used as definitive hosts of Schistosoma.

  8. Murine models of Streptococcus pyogenes infection.

    PubMed

    Roberts, Samantha; Scott, June R; Husmann, Linda K; Zurawski, Christine A

    2006-09-01

    This unit describes procedures for testing virulence of Streptococcus pyogenes in mice. S. pyogenes is an important human pathogen and causes one of the most common childhood diseases. The syndromes that result from S. pyogenes infection are diverse, ranging from mild, superficial throat or skin infection to severe, invasive disea/se that is often lethal. Thus, a greater understanding of the virulence factors of this bacterium and development of modalities to prevent or relieve the infections it causes are important. Since S. pyogenes is a strictly human pathogen (with the exception of a single strain), the value of all animal models is limited. This unit describes a model for long-term throat colonization following the natural route of infection (inhalation), one for pneumonia and systemic dissemination following intratracheal inoculation, and one for systemic dissemination following the more natural route of skin infection. In addition, methods are presented for culturing S. pyogenes from tissues of the infected animal.

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

    PubMed

    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; Kempf, Volkhard A J

    2015-12-28

    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.

  10. 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

  11. Macrophage infection models for Mycobacterium tuberculosis.

    PubMed

    Johnson, Benjamin K; Abramovitch, Robert B

    2015-01-01

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

  12. 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

  13. Novel mixed NOP/MOP agonist BU08070 alleviates pain and inhibits gastrointestinal motility in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms.

    PubMed

    Sobczak, Marta; Cami-Kobeci, Gerta; Sałaga, Maciej; Husbands, Stephen M; Fichna, Jakub

    2014-08-05

    The opioid and nociceptin systems play a crucial role in the maintenance of homeostasis in the gastrointestinal (GI) tract. The aim of this study was to characterize the effect of BU08070, a novel mixed MOP/NOP agonist, on mouse intestinal contractility in vitro and GI motility in vivo in physiological conditions and in animal models mimicking symptoms of irritable bowel syndrome (IBS), including diarrhea and abdominal pain. The effect of BU08070 on muscle contractility in vitro was characterized in the ileum and colon. To assess the effect of BU08070 in vivo, the following parameters were assessed: whole GI transit, gastric emptying, geometric center, colonic bead expulsion, fecal pellet output and time to castor oil-induced diarrhea. The antinociceptive activity of BU08070 was characterized in the mustard oil (MO)-induced abdominal pain model and the writhing test, alone and in the presence of MOP and NOP antagonists. in vitro, BU08070 (10(-10)-10(-6) M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent manner. in vivo, BU08070 prolonged the whole GI transit and inhibited colonic bead expulsion. The antitransit and antidiarrheal effects of BU08070 were observed already at the dose of 0.1 mg/kg (i.p.). BU08070 reversed hypermotility and reduced pain in mouse models mimicking IBS-D symptoms. Our results suggest that BU08070 has a potential of becoming an efficient drug in IBS-D therapy. Here we also validate mixed NOP/MOP receptor targeting as possible future treatment of functional GI diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

    PubMed

    Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub

    2017-04-01

    Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10(-10) to 10(-6)M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Novel mixed NOP/MOP agonist BU08070 alleviates pain and inhibits gastrointestinal motility in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

    PubMed Central

    Sobczak, Marta; Cami-Kobeci, Gerta; Sałaga, Maciej; Husbands, Stephen M.; Fichna, Jakub

    2015-01-01

    Background The opioid and nociceptin systems play a crucial role in the maintenance of homeostasis in the gastrointestinal (GI) tract. The aim of this study was to characterize the effect of BU08070, a novel mixed MOP/NOP agonist, on mouse intestinal contractility in vitro and GI motility in vivo in physiological conditions and in animal models mimicking symptoms of irritable bowel syndrome (IBS), including diarrhea and abdominal pain. Methods The effect of BU08070 on muscle contractility in vitro was characterized in the ileum and colon. To assess the effect of BU08070 in vivo, the following parameters were assessed: whole GI transit, gastric emptying, geometric center, colonic bead expulsion, fecal pellet output and time to castor oil-induced diarrhea. The antinociceptive activity of BU08070 was characterized in the mustard oil (MO)-induced abdominal pain model and the writhing test, alone and in the presence of MOP and NOP antagonists. Results In vitro, BU08070 (10−10–10−6 M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent manner. In vivo, BU08070 prolonged the whole GI transit and inhibited colonic bead expulsion. The antitransit and antidiarrheal effect of BU08070 was observed already at the dose of 0.1 mg/kg (i.p.). BU08070 reversed hypermotility and reduced pain in mouse models mimicking IBS-D symptoms. Conclusion Our results suggest that BU08070 has a potential of becoming an efficient drug in IBS-D therapy. Here we also validate mixed NOP/MOP receptor targeting as possible future treatment of functional GI diseases. PMID:24815321

  16. 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.

  17. Sea-lice infection models for fishes.

    PubMed

    Frazer, L Neil

    2008-10-01

    As free-living sea-lice larvae are difficult to sample directly, lice abundances on fish have recently been used to study larvae in the water. In the KLV problem, juvenile wild salmon migrate past a salmon farm, and the change of infection with distance along the migration route is used to estimate larvae production from the farm. In the farm problem, time-varying infection of sea-cage fish is used to estimate the time-variation of free-living larvae in waters near the farm. Both inverse problems require good forward models for infection. In the farm problem, hosts are relatively large and lice pathogenesis is seldom mortal, whereas in the KLV problem hosts are small and lice-induced host mortality can affect lice abundance; thus, infection models for the farm problem are special cases of models for the KLV problem. Here I give an infection model for the KLV problem that explicitly includes lice clumping and host mortality, showing that Krkosek et al. (Proc R Soc B 272:689-696, 2005) (KLV) probably underestimated larvae production by the salmon farm, and further, that if lice development rates were known from laboratory data, lice abundance field data could be directly inverted for lice-induced host mortality during migration. If lice-induced host mortality is negligible, or if lice are Poisson distributed, infection models of arbitrary complexity reduce to Erlang models. I give two useful Erlang models with their solutions for non-zero initial conditions.

  18. Transmigration and phagocytosis of macrophages in an airway infection model using four-dimensional techniques.

    PubMed

    Ding, Peishan; Wu, Huimei; Fang, Lei; Wu, Ming; Liu, Rongyu

    2014-07-01

    During infection, recruited phagocytes transmigrate across the epithelium to remove the pathogens deposited on the airway surface. However, it is difficult to directly observe cellular behaviors (e.g., transmigration) in single-cell layer cultures or in live animals. Combining a three-dimensional (3D) cell coculture model mimicking airway infection with time-lapse confocal imaging as a four-dimensional technique allowed us to image the behaviors of macrophages in 3D over time. The airway infection model was moved to a glass-bottomed dish for live-cell imaging by confocal laser scanning microscopy. Using time-lapse confocal imaging, we recorded macrophages transmigrating across the polyethylene terephthalate (PET) membrane of the inserts through the 5-μm pores in the PET membrane. Macrophages on the apical side of the insert exhibited essentially three types of movements, one of which was transmigrating across the epithelial cell monolayer and arriving at the surface of monolayer. We found that adding Staphylococcus aureus to the model increased the transmigration index but not the transmigration time of the macrophages. Only in the presence of S. aureus were the macrophages able to transmigrate across the epithelial cell monolayer. Apical-to-basal transmigration of macrophages was visualized dynamically. We also imaged the macrophages phagocytizing S. aureus deposited on the surface of the monolayer in the airway infection model. This work provides a useful tool to study the cellular behaviors of immune cells spatially and temporally during infection.

  19. 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.

  20. Glycogen synthase kinase-3beta heterozygote knockout mice as a model of findings in postmortem schizophrenia brain or as a model of behaviors mimicking lithium action: negative results.

    PubMed

    Bersudsky, Yuly; Shaldubina, Alona; Kozlovsky, Nitzan; Woodgett, James R; Agam, Galila; Belmaker, R H

    2008-05-01

    In mice glycogen synthase kinase (GSK)-3beta heterozygote knockout status was reported to cause reduced immobility in the Porsolt forced swim test and reduced amphetamine-induced hyperactivity, behaviors that mimic the effects of lithium. GSK-3beta protein and mRNA level and activity have been reported to be reduced in the postmortem brain of schizophrenia patients and this could suggest the involvement of GSK-3beta in the etiology of schizophrenia. However, apomorphine-induced stereotyping was reported to be unchanged in GSK-3beta heterozygote (HZ) knockout (KO) mice. As such behaviors are not always robust, study in another laboratory seemed indicated. Motor activity and coordination were assessed in the rotarod test. Behavior was studied in the following tests: pilocarpine-induced seizures model for lithium action, Porsolt forced swim test, tail suspension test, elevated plus-maze, large open field, startle response and prepulse inhibition of acoustic startle response, amphetamine-induced hyperactivity, and apomorphine-induced stereotypic climbing. We could not confirm the report that GSK-3beta HZ KO mice exhibit reduced immobility in the Porsolt forced swim or reduced amphetamine-induced hyperactivity in a manner mimicking the behavioral effects of lithium. We did not find increased apomorphine-induced stereotypic climbing or disruption of prepulse inhibition, suggesting that human postmortem findings regarding GSK-3beta in schizophrenia are not mediated by changes in dopamine receptors and are not the cause of prepulse inhibition deficits in schizophrenia. These data do not support the role of GSK-3beta in schizophrenia or in the mechanism of therapeutic action of lithium. Although differences in the genetic background of the GSK-3beta HZ KOs used in the present study compared with that of the previous study could be responsible, such results could suggest that the previously reported effects of GSK-3beta knockout on behavior are not robust.

  1. 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

  2. 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

  3. Apoptosis in virus infection dynamics models

    PubMed Central

    Fan, Ruili; Dong, Yueping; Huang, Gang; Takeuchi, Yasuhiro

    2014-01-01

    In this paper, on the basis of the simplified two-dimensional virus infection dynamics model, we propose two extended models that aim at incorporating the influence of activation-induced apoptosis which directly affects the population of uninfected cells. The theoretical analysis shows that increasing apoptosis plays a positive role in control of virus infection. However, after being included the third population of cytotoxic T lymphocytes immune response in HIV-infected patients, it shows that depending on intensity of the apoptosis of healthy cells, the apoptosis can either promote or comfort the long-term evolution of HIV infection. Further, the discrete-time delay of apoptosis is incorporated into the pervious model. Stability switching occurs as the time delay in apoptosis increases. Numerical simulations are performed to illustrate the theoretical results and display the different impacts of a delay in apoptosis. PMID:24963975

  4. 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

  5. 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.

  6. 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.

  7. Human lung ex vivo infection models.

    PubMed

    Hocke, Andreas C; Suttorp, Norbert; Hippenstiel, Stefan

    2017-03-01

    Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.

  8. 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

  9. Experimental models for hepatitis C viral infection.

    PubMed

    Boonstra, Andre; van der Laan, Luc J W; Vanwolleghem, Thomas; Janssen, Harry L A

    2009-11-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The majority of infected individuals develop a persistent infection, which is associated with a high risk of liver cirrhosis and hepatocellular carcinoma. Since its discovery 20 years ago, progress in our understanding of this virus has been suboptimal due to the lack of good model systems. However, in the past decade this has greatly accelerated with the development of various in vitro cell culture systems and in vivo small-animal models. These systems have made a major impact on the field of HCV research, and have provided important breakthroughs in our understanding of HCV infection and replication. Importantly, the in vitro cell culture systems and the small-animal models have allowed preclinical testing of numerous novel antiviral compounds for the treatment of chronic HCV infection. In this article, we give an overview of current models, discuss their limitations, and provide future perspectives for research directed at the prevention and cure of hepatitis C.

  10. Drosophila melanogaster model for Mycobacterium abscessus infection.

    PubMed

    Oh, Chun-Taek; Moon, Cheol; Jeong, Myeong Seon; Kwon, Seung-Hae; Jang, Jichan

    2013-11-01

    Mycobacterium abscessus is a human pathogen that is responsible for a broad spectrum of tissue infections and disseminated infections in immunodeficient patients. This pathogen is one of the most resistant organisms to chemotherapeutic agents. Therefore, we tested the hypothesis that the fruit fly, Drosophila melanogaster, is a genetically tractable model host for M. abscessus. In this context, we infected D. melanogaster with M. abscessus. This M. abscessus infection results in dissemination in the fly body, followed by death, which is accompanied by severe indirect flight muscle and brain damage. Our data show that M. abscessus can grow and replicate in D. melanogaster w(1118) and that it elicited a humoral immune response, especially of the Toll antimicrobial peptide pathway. To the best of our knowledge, this is the first report that mycobacteria induce the production of antimicrobial peptides in D. melanogaster.

  11. Bone involvement and abcess formation by neutrophil-rich CD30+ anaplastic large-cell lymphoma mimicking skeletal infection in an AIDS patient.

    PubMed

    Mira, José A; Fernández-Alonso, Jorge; Macías, Juan; Sáez, Carmen; Japón, Miguel A; Pereda, Teresa; Pineda, Juan A

    2003-07-01

    Neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) is a rare pathological entity without distinct clinical behavior. Twelve cases of neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) have been reported, three of them were HIV-infected patients. All these reports stressed the presence of neutrophil infiltration as a new morphologic feature of CD30+ ALCL. Only one case of cutaneous involvement presented with microabscess formation. We describe a case of neutrophil-rich CD30+ ALCL in an AIDS patient with a clinical picture determined by the massive neutrophil infiltration of the tumor without necrosis nor local infection, but with the formation of abscesses.

  12. 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.

  13. 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.

  14. Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

    PubMed

    Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

    2014-07-01

    The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders.

  15. 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.

  16. Zebrafish: Modeling for Herpes Simplex Virus Infections

    PubMed Central

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

    2014-01-01

    Abstract 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. PMID:24266790

  17. Nonlinear hierarchical modeling of experimental infection data.

    PubMed

    Singleton, Michael D; Breheny, Patrick J

    2016-08-01

    In this paper, we propose a nonlinear hierarchical model (NLHM) for analyzing longitudinal experimental infection (EI) data. The NLHM offers several improvements over commonly used alternatives such as repeated measures analysis of variance (RM-ANOVA) and the linear mixed model (LMM). It enables comparison of relevant biological properties of the course of infection including peak intensity, duration and time to peak, rather than simply comparing mean responses at each observation time. We illustrate the practical benefits of this model and the insights it yields using data from experimental infection studies on equine arteritis virus. Finally, we demonstrate via simulation studies that the NLHM substantially reduces bias and improves the power to detect differences in relevant features of the infection response between two populations. For example, to detect a 20% difference in response duration between two groups (n=15) in which the peak time and peak intensity were identical, the RM-ANOVA test had a power of just 11%, and LMM a power of just 12%. By comparison, the nonlinear model we propose had a power of 58% in the same scenario, while controlling the Type I error rate better than the other two methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Experimental rabbit models of Chlamydia pneumoniae infection.

    PubMed Central

    Moazed, T. C.; Kuo, C.; Patton, D. L.; Grayston, J. T.; Campbell, L. A.

    1996-01-01

    Chlamydia pneumoniae (TWAR), a common cause of acute respiratory disease in humans, has recently been associated with coronary and aortic atherosclerosis. In this study, we evaluated rabbit models of chlamydial infection to investigate the pathogenesis of C. pneumoniae infection. New Zealand White rabbits were inoculated intranasally and intratracheally with C. pneumoniae, strain AR-39, and primary and repeated infection were assessed. After a single inoculation, lung pathology was characterized by a moderate self-resolving interstitial pneumonia with bronchiolitis of 21 days in duration. Chlamydial DNA was detected by polymerase chain reaction (PCR) intermittently in the upper respiratory tract and lung tissue through day 21 postinoculation, spleen tissue at day 14, and peripheral blood mononuclear cells at days 3 and 21. After repeated inoculations, chlamydial DNA was detected by PCR in the upper respiratory tract and lung tissue through day 42. Lung lesions consisted of multifocal interstitial mononuclear cell aggregates that persisted up to day 42. Watanabe heritable hyperlipidemic rabbits were less susceptible to C. pneumoniae infection. After multiple inoculations of Watanabe rabbits, C. pneumoniae was detected by PCR and/or immunocytochemistry until day 21. In conclusion, C. pneumoniae induced a moderate respiratory infection in these rabbit models. Images Figure 1 Figure 2 Figure 3 PMID:8579129

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

    PubMed

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

    2014-01-01

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

  20. 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

  1. Solution of an infection model near threshold

    NASA Astrophysics Data System (ADS)

    Kessler, David A.; Shnerb, Nadav M.

    2007-07-01

    We study the susceptible-infected-recovered model of epidemics in the vicinity of the threshold infectivity. We derive the distribution of total outbreak size in the limit of large population size N . This is accomplished by mapping the problem to the first passage time of a random walker subject to a drift that increases linearly with time. We recover the scaling results of Ben-Naim and Krapivsky that the effective maximal size of the outbreak scales as N2/3 , with the average scaling as N1/3 , with an explicit form for the scaling function.

  2. Exploration of a physiologically-inspired hearing-aid algorithm using a computer model mimicking impaired hearing.

    PubMed

    Jürgens, Tim; Clark, Nicholas R; Lecluyse, Wendy; Meddis, Ray

    2016-01-01

    To use a computer model of impaired hearing to explore the effects of a physiologically-inspired hearing-aid algorithm on a range of psychoacoustic measures. A computer model of a hypothetical impaired listener's hearing was constructed by adjusting parameters of a computer model of normal hearing. Absolute thresholds, estimates of compression, and frequency selectivity (summarized to a hearing profile) were assessed using this model with and without pre-processing the stimuli by a hearing-aid algorithm. The influence of different settings of the algorithm on the impaired profile was investigated. To validate the model predictions, the effect of the algorithm on hearing profiles of human impaired listeners was measured. A computer model simulating impaired hearing (total absence of basilar membrane compression) was used, and three hearing-impaired listeners participated. The hearing profiles of the model and the listeners showed substantial changes when the test stimuli were pre-processed by the hearing-aid algorithm. These changes consisted of lower absolute thresholds, steeper temporal masking curves, and sharper psychophysical tuning curves. The hearing-aid algorithm affected the impaired hearing profile of the model to approximate a normal hearing profile. Qualitatively similar results were found with the impaired listeners' hearing profiles.

  3. Acute-onset epilepsy triggered by fever mimicking FIRES (febrile infection-related epilepsy syndrome): the role of protocadherin 19 (PCDH19) gene mutation.

    PubMed

    Specchio, Nicola; Fusco, Lucia; Vigevano, Federico

    2011-11-01

    To report differences and similarities between febrile infection-related epilepsy syndrome (FIRES) and epilepsy in female patients with protocadherin 19 (PCDH19) mutation. These are two recently described epileptic conditions characterized by drug-resistant epilepsy and cognitive impairment. We report, as exemplification, one of our patients with acute-onset epilepsy triggered by fever with clinical course resembling FIRES, but with a missense mutation of PCDH19 gene. The clinical characteristics of this patient are similar to those reported for FIRES. We believe that female patients with febrile acute-onset epilepsy resembling FIRES are potential PCDH19 mutation carriers. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  4. Additive model for the second harmonic generation hyperpolarizability applied to a collagen-mimicking peptide (Pro-Pro-Gly)10.

    PubMed

    Loison, C; Simon, D

    2010-07-29

    Second harmonic generation (SHG) spectrometry has been recently applied to investigate the structure of proteins and sugars (collagen, myosin, starch, etc.). The interpretation of experimental data at the molecular length-scale remains often qualitative because of the difficulty to model the SHG signal of such large molecules. Simpson and co-workers proposed to estimate the hyperpolarizability of the peptide backbone as the sum of the individual hyperpolarizabilities of the peptide bonds. This article discusses the hyperpolarizabilities obtained using such an additive model for a peptide (Pro-Pro-Gly)(10) modeling collagen, for which experimental hyperpolarizabilities have been measured and modeled recently. To investigate possible parameters for the model, we performed time-dependent density functional theory (TDDFT) calculations of the hyperpolarizability of a few molecules containing one peptide bond. In a second step, the additive model is applied. The results produced using different input parameters are compared to each other and to experimental data. For the chosen peptide, the additive model using N-methylacetamide as a building block agrees qualitatively with hyper-Rayleigh scattering data. The results emphasize the need for more reference data to test the additivity hypothesis and the transferability of the parameters to other secondary structure of proteins.

  5. Reactive arthritis mimicking inflammatory bowel disease arthritis: a challenging diagnosis.

    PubMed

    Trabulo, D; Mangualde, J; Cremers, I; Oliveira, A P

    2014-01-01

    Reactive arthritis comprises a subgroup of infection-associated arthritis which occurs after genitourinary or gastrointestinal tract infection in genetically susceptible hosts. Studies have proposed Salmonella, Shigella or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 is a well recognised best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella goldcoast enteritis, mimicking inflammatory bowel disease arthritis.

  6. Animal models of respiratory syncytial virus infection.

    PubMed

    Taylor, Geraldine

    2017-01-11

    Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore

  7. Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models.

    PubMed

    Tevis, Kristie M; Cecchi, Ryan J; Colson, Yolonda L; Grinstaff, Mark W

    2017-03-01

    Tumor associated macrophages (TAMs) are critical stromal components intimately involved with the progression, invasion, and metastasis of cancer cells. To address the need for an in vitro system that mimics the clinical observations of TAM localizations and subsequent functional performance, a cancer cell/macrophage spheroid model is described. The central component of the model is a triple negative breast cancer spheroid embedded in a three-dimensional collagen gel. Macrophages are incorporated in two different ways. The first is a heterospheroid, a spheroid containing both tumor cells and macrophages. The heterospheroid mimics the population of TAMs infiltrated into the tumor mass, thus being exposed to hypoxia and metabolic gradients. In the second model, macrophages are diffusely seeded in the collagen surrounding the spheroid, thus modeling TAMs in the cancer stroma. The inclusion of macrophages as a heterospheroid changes the metabolic profile, indicative of synergistic growth. In contrast, macrophages diffusely seeded in the collagen bear the same profile regardless of the presence of a tumor cell spheroid. The macrophages in the heterospheroid secrete EGF, a cytokine critical to tumor/macrophage co-migration, and an EGF inhibitor decreases the metabolic activity of the heterospheroid, which is not observed in the other systems. The increased secretion of IL-10 indicates that the heterospheroid macrophages follow an M2/TAM differentiation pathway. Lastly, the heterospheroid exhibits resistance to paclitaxel. In summary, the collagen embedded heterospheroid model promotes TAM-like characteristics, and will be of utility in cancer biology and drug discovery.

  8. Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment.

    PubMed

    Tarallo, Sonia; Beltramo, Elena; Berrone, Elena; Porta, Massimo

    2012-12-01

    Pericytes regulate vascular tone, perfusion pressure and endothelial cell (EC) proliferation in capillaries. Thiamine and benfotiamine counteract high glucose-induced damage in vascular cells. We standardized two human retinal pericyte (HRP)/EC co-culture models to mimic the diabetic retinal microvascular environment. We aimed at evaluating the interactions between co-cultured HRP and EC in terms of proliferation/apoptosis and the possible protective role of thiamine and benfotiamine against high glucose-induced damage. EC and HRP were co-cultured in physiological glucose and stable or intermittent high glucose, with or without thiamine/benfotiamine. No-contact model: EC were plated on a porous membrane suspended into the medium and HRP on the bottom of the same well. Cell-to-cell contact model: EC and HRP were plated on the opposite sides of the same membrane. Proliferation (cell counts and DNA synthesis), apoptosis and tubule formation in Matrigel were assessed. In the no-contact model, stable high glucose reduced proliferation of co-cultured EC/HRP and EC alone and increased co-cultured EC/HRP apoptosis. In the contact model, both stable and intermittent high glucose reduced co-cultured EC/HRP proliferation and increased apoptosis. Stable high glucose had no effects on HRP in separate cultures. Both EC and HRP proliferated better when co-cultured. Thiamine and benfotiamine reversed high glucose-induced damage in all cases. HRP are sensitive to soluble factors released by EC when cultured in high glucose conditions, as suggested by conditioned media assays. In the Matrigel models, addition of thiamine and benfotiamine re-established the high glucose-damaged interactions between EC/HRP and stabilized microtubules.

  9. Modeling human influenza infection in the laboratory.

    PubMed

    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.

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. Severe emphysematous pyelonephritis mimicking intestinal obstruction.

    PubMed

    Sun, Ji Ning; Zhang, Bao Long; Yu, Hai Yan; Wang, Bin

    2015-12-01

    Emphysematous pyelonephritis is a severe necrotizing infection characterized by the presence of gas and/or fluid in the renal parenchyma, collecting system, or perirenal tissues. Emphysematous pyelonephritis with approximately 15 cm air-fluid level, diffused ureteral involvement, and the accumulation of gas in liver and peritoneal cavity is very rare. Here, we reported a severe emphysematous pyelonephritis with multiple huge air-fluid level mimicking intestinal obstruction and with the accumulation of gas in liver and ureter in computed tomography imaging. The patient was successfully managed by percutaneous nephrostomy combined with medical treatment.

  13. A new model of experimental fibrosis in hindlimb skeletal muscle of adult mdx mouse mimicking muscular dystrophy.

    PubMed

    Desguerre, Isabelle; Arnold, Ludovic; Vignaud, Alban; Cuvellier, Sylvain; Yacoub-Youssef, Houda; Gherardi, Romain K; Chelly, Jamel; Chretien, Fabrice; Mounier, Rémi; Ferry, Arnaud; Chazaud, Bénédicte

    2012-06-01

    Duchenne Muscular Dystrophy (DMD) is characterized by the lack of dystrophin that leads to severe myofiber degeneration. We have shown that endomysial fibrosis is correlated with age at ambulation loss in DMD patients. However, the dystrophin-deficient mdx mouse does not have fibrotic lesions in adult limb muscles. Here, we describe a model of chronic mechanical muscle injury that triggers chronic lesions in mdx hindlimb muscle. Micromechanical injuries were performed daily in tibialis anterior muscles for 2 weeks. Endomysial fibrosis appeared beginning 1 week post-injury, remained stable for 3 months and was associated with loss of specific maximal force. Fibrosis was associated with an increased expression of factors involved in fibrogenesis including α-smooth muscle actin, connective tissue growth factor, and lysyl oxidase, which colocalized with collagen deposits. This induced fibrotic dystrophic model may be useful to study mechanisms of fibrosis in dystrophinopathies and to evaluate antifibrotic treatments. Copyright © 2012 Wiley Periodicals, Inc.

  14. A functional model of extradiol-cleaving catechol dioxygenases: mimicking the 2-his-1-carboxylate facial triad.

    PubMed

    Paria, Sayantan; Halder, Partha; Paine, Tapan Kanti

    2010-05-17

    The synthesis and characterization of an iron-catecholate model complex of a tridentate 2-N-1-carboxylate ligand derived from L-proline are reported. The X-ray crystal structure of the complex [(L)(3)Fe(3)(DBC)(3)] (1) (where L is 1-(2-pyridylmethyl)pyrrolidine-2-carboxylate and DBC is the dianion of 3,5-di-tert-butyl catechol) reveals that the tridentate ligand binds to the iron center in a facial manner and mimics the 2-his-1-carboxylate facial triad motif observed in extradiol-cleaving catechol dioxygenases. The iron(III)-catecholate complex (1) reacts with dioxygen in acetonitrile in ambient conditions to cleave the C-C bond of catecholate. In the reaction, an equal amount of extra- and intradiol cleavage products are formed without any auto-oxidation product. The iron-catecholate complex is a potential functional model of extradiol-cleaving catechol dioxygenases.

  15. Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse model mimicking oral tumorigenesis.

    PubMed

    Chang, Nai-Wen; Pei, Ren-Jeng; Tseng, Hsien-Chang; Yeh, Kun-Tu; Chan, Hsu-Chin; Lee, Miau-Rong; Lin, Chingju; Hsieh, Wen-Tsong; Kao, Ming-Ching; Tsai, Ming-Hsui; Lin, Chin-Fen

    2010-01-05

    The aim of this study was to establish an effective mouse model of oral cancer and to use this model to identify potential markers of oral tumor progression. C57BL/6JNarl mice were treated with arecoline, 4-nitroquinoline 1-oxide (4-NQO), or both arecoline and 4-NQO in high and low doses for 8 weeks to induce oral tumor. The induced oral lesions were observed for 20 weeks to assess the efficiency of cancer induction and survival rate of the mice. In addition, two target proteins that are frequently overexpressed during tongue cancer tumorigenesis, alphaB-crystallin and Hsp27, were examined by immunohistochemical analysis. In mice exposed to 4-NQO (200 microg/mL) and arecoline (500 microg/mL), the tongue lesions showed evidence of hyperplasia, papilloma, dysplasia, and carcinoma, and the lesions were pathologically similar to those lesions in human oral cancer. The tongue tumor incidence rate was 100% in mice exposed to concomitant 4-NQO (200 microg/mL) and arecoline (500 microg/mL) treatment, 57% in mice exposed to 4-NQO only, and 0% in mice exposed to arecoline only. Immunohistochemical analysis demonstrated that, consistent with human studies, alphaB-crystallin and Hsp27 were upregulated in murine oral tumors. In conclusion, we have established a powerful animal model that enables the study of the promoting effects of arecoline on tongue tumorigenesis. Data subsequently attained from this mouse model support a role for alphaB-crystallin and Hsp27 as clinical markers for tumor progression.

  16. Dengue human infection models supporting drug development.

    PubMed

    Whitehorn, James; Van, Vinh Chau Nguyen; Simmons, Cameron P

    2014-06-15

    Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  17. Mimicking emotions: how 3-12-month-old infants use the facial expressions and eyes of a model.

    PubMed

    Soussignan, Robert; Dollion, Nicolas; Schaal, Benoist; Durand, Karine; Reissland, Nadja; Baudouin, Jean-Yves

    2017-08-04

    While there is an extensive literature on the tendency to mimic emotional expressions in adults, it is unclear how this skill emerges and develops over time. Specifically, it is unclear whether infants mimic discrete emotion-related facial actions, whether their facial displays are moderated by contextual cues and whether infants' emotional mimicry is constrained by developmental changes in the ability to discriminate emotions. We therefore investigate these questions using Baby-FACS to code infants' facial displays and eye-movement tracking to examine infants' looking times at facial expressions. Three-, 7-, and 12-month-old participants were exposed to dynamic facial expressions (joy, anger, fear, disgust, sadness) of a virtual model which either looked at the infant or had an averted gaze. Infants did not match emotion-specific facial actions shown by the model, but they produced valence-congruent facial responses to the distinct expressions. Furthermore, only the 7- and 12-month-olds displayed negative responses to the model's negative expressions and they looked more at areas of the face recruiting facial actions involved in specific expressions. Our results suggest that valence-congruent expressions emerge in infancy during a period where the decoding of facial expressions becomes increasingly sensitive to the social signal value of emotions.

  18. Hosting infection: experimental models to assay Candida virulence.

    PubMed

    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.

  19. Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

    PubMed

    Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

    2017-07-15

    Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10(7) to 10(9) 50% tissue culture infective doses (TCID50) consistently infected all the animals, and many monkeys receiving 10(8) or 10(9) TCID50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines.IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

  20. 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

  1. Mimicking the Moon

    NASA Image and Video Library

    2014-11-03

    When Galileo first observed Venus displaying a crescent phase, he excitedly wrote to Kepler (in anagram) of Venus mimicking the moon-goddess. He would have been delirious with joy to see Saturn and Titan, seen in this image, doing the same thing. More than just pretty pictures, high-phase observations -- taken looking generally toward the Sun, as in this image -- are very powerful scientifically since the way atmospheres and rings transmit sunlight is often diagnostic of compositions and physical states. In this example, Titan's crescent nearly encircles its disk due to the small haze particles high in its atmosphere refracting the incoming light of the distant Sun. This view looks toward the sunlit side of the rings from about 3 degrees above the ringplane. The image was taken in violet light with the Cassini spacecraft wide-angle camera on Aug. 11, 2013. The view was obtained at a distance of approximately 1.1 million miles (1.7 million kilometers) from Saturn and at a Sun-Saturn-spacecraft, or phase, angle of 154 degrees. Image scale is 64 miles (103 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA18291

  2. 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

  3. 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.

  4. Disseminated Blastomycosis Mimicking Malignancy.

    PubMed

    Hsu, Jennifer L; Tjarks, B Joel; Berg, Aaron; Oliver, Tony

    2017-04-01

    Blastomycosis is an endemic fungal infection commonly found within the Mississippi and Ohio River basins and Great Lakes region. While patients typically present with acute pneumonia, Blastomyces dermatitidis has the potential to spread hematogenously, resulting in disseminated infection of multiple organs. In this report, we describe a 57-year-old male with disseminated blastomycosis acquired in South Dakota. The diagnostic evaluation was confounded by concern for malignancy given the involvement of multiple locations, including brain, lungs, adrenal glands, and testes. Despite aggressive therapy with amphotericin B, the patient succumbed to this infection. Copyright© South Dakota State Medical Association.

  5. Mouse models of rhinovirus infection and airways disease.

    PubMed

    Bartlett, Nathan W; Singanayagam, Aran; Johnston, Sebastian L

    2015-01-01

    Mouse models are invaluable tools for gaining insight into host immunity during virus infection. Until recently, no practical mouse model for rhinovirus infection was available. Development of infection models was complicated by the existence of distinct groups of viruses that utilize different host cell surface proteins for binding and entry. Here, we describe mouse infection models, including virus purification and measurement of host immune responses, for representative viruses from two of these groups: (1) infection of unmodified Balb/c mice with minor group rhinovirus serotype 1B (RV-1B) and (2) infection of transgenic Balb/c mice with major group rhinovirus serotype 16 (RV-16).

  6. 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

  7. Estrogen-mimicking isoflavone genistein prevents bone loss in a rat model of obstructive sleep apnea-hypopnea syndrome.

    PubMed

    Song, Lige; Liang, Xiao; Zhou, Yun

    2014-01-01

    Intermittent hypoxia was introduced to mimic obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. Then, bone mass, bone strength and bone turnover were evaluated, and the influence of genistein on bone mass reduction was investigated in these rats. OSAHS animal model was established via chronic intermittent hypoxia, and genistein (2.5 mg/kg/day) was used to treat OSAHS rats. The bone mineral density (BMD), bone Histomorphometric indicators, bone biomechanics and expressions of genes related to bone formation and resorption (Runx2, Col I, ALP, Osteocalcin, OPG, RANKL and TRAP-5b) were measured after treatment. The BMD in OSAHS+OVX group was significantly lower than that in OVX group (P<0.05). The BMD in OSAHS+OVX+Genistein group was markedly increased when compared with OSAHS+OVX group (P<0.05), accompanied by partial improvement of the OSAHS induced damage to the lumbar biomechanics. In OSAHS+OVX group, the expressions of Runx2, Col I, ALP and Osteocalcin were significantly reduced when compared with OVX group, and rats in OSAHS+OVX+Genistein group had significantly higher expressions of Runx2, Col I, ALP and Osteocalcin and reduced TRAP-5b expression as compared to OSAHS+OVX group (P<0.05). Genistein can improve the reduction in bone mass and bone strength due to OSAHS in OVX rats, which may be attributed to the increase in bone formation and inhibition of bone resorption. Our findings suggest that genistein may be used to treat and prevent osteoporosis in postmenopausal women with OSAHS.

  8. Simple animal model of Helicobacter pylori infection.

    PubMed

    Werawatganon, Duangporn

    2014-06-07

    Helicobacter pylori (H. pylori) has become accepted as a human pathogen for the development of gastritis and gastroduodenal ulcer. To develop a simple rat model of chronic H. pylori infection, male Sprague-Dawley rats were pretreated with streptomycin suspended in tap water (5 mg/mL) for 3 d. The rats were inoculated by gavage at 1 mL/rat with H. pylori suspension (5 × 10(8)-5 × 10(10) CFU/mL) twice daily at an interval of 4 h for three consecutive days. Two weeks after inoculation, rats were sacrificed and the stomachs were removed. Antral biopsies were performed for urease test and the stomachs were taken for histopathology. Successful H. pylori inoculation was defined as a positive urease test and histopathology. We reported a 69.8%-83.0% success rate for H. pylori infection using the urease test, and hematoxylin and eosin staining confirmed the results. Histopathological analysis detected bacteria along the mucous lining of the surface epithelium and crypt lumen and demonstrated mild to moderate gastric inflammation in successfully inoculated rats. We developed a simple rat model of chronic H. pylori infection for research into gastric microcirculatory changes and therapy with plant products.

  9. Infectivity model verification studies, annual report - 1981

    SciTech Connect

    McGrath, J.J.

    1982-01-01

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

  10. Spherical boson stars as black hole mimickers

    SciTech Connect

    Guzman, F. S.; Rueda-Becerril, J. M.

    2009-10-15

    We present spherically symmetric boson stars as black hole mimickers based on the power spectrum of a simple accretion disk model. The free parameters of the boson star are the mass of the boson and the fourth-order self-interaction coefficient in the scalar field potential. We show that even if the mass of the boson is the only free parameter, it is possible to find a configuration that mimics the power spectrum of the disk due to a black hole of the same mass. We also show that for each value of the self-interaction a single boson star configuration can mimic a black hole at very different astrophysical scales in terms of the mass of the object and the accretion rate. In order to show that it is possible to distinguish one of our mimickers from a black hole, we also study the deflection of light.

  11. Cutaneous manifestations of human T cell leukemia virus type I infection in an experimental model.

    PubMed

    Simpson, R M; Leno, M; Hubbard, B S; Kindt, T J

    1996-03-01

    Skin diseases ranging from infective dermatitis to cutaneous lymphoma have been associated with human T cell leukemia virus (HTLV) type I. A generalized exfoliative papillated dermatopathy occurred in a rabbit 20 months into a course of chronic HTLV-I infection. Biopsies revealed epidermotropic T cell infiltrates, including Sezary-like cells, that resulted in a pattern mimicking cutaneous T cell lymphoma. HTLV-I was isolated from affected skin, and virus expression was detected in cutaneous cultures. Sezary-like cells also occurred in circulation. Interleukin-2-independent lymphocyte cultures, established from blood exhibiting elevated CD8 T cell levels and CD25 expression, had polyclonal integration of provirus. The findings are similar to those in evolving adult T cell leukemia lymphoma and may represent a prelymphomatous change. The cutaneous lymphoproliferative lesion resulted from HTLV-I infection and further establishes the New Zealand White rabbit inoculated with the RH/K34 cell line as a suitable model for investigation of HTLV-I pathogenesis.

  12. 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.

  13. 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.

  14. 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

  15. Mouse infection models for space flight immunology.

    PubMed

    Chapes, Stephen Keith; Ganta, Roman Reddy

    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.

  16. Pulmonary Actinomycosis Mimicking Pulmonary Aspergilloma and a Brief Review of the Literature

    PubMed Central

    Higashi, Yoshitsugu; Nakamura, Shigeki; Ashizawa, Nobuyuki; Oshima, Kazuhiro; Tanaka, Akitaka; Miyazaki, Taiga; Izumikawa, Koichi; Yanagihara, Katsunori; Yamamoto, Yoshihiro; Miyazaki, Yoshitsugu; Mukae, Hiroshi; Kohno, Shigeru

    2017-01-01

    Pulmonary actinomycosis is a rare pulmonary infection that often exhibits unspecific symptoms and radiological findings. We herein report a case of pulmonary actinomycosis that mimicked pulmonary aspergilloma in an immunocompetent patient. PMID:28202870

  17. A silkworm model of pathogenic bacterial infection.

    PubMed

    Kaito, C; Sekimizu, K

    2007-10-01

    Silkworms are invertebrate animals that are killed by bacteria pathogenic against humans, such as Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, and Vibrio cholerae. Injection into the hemolymph of antibiotics that are clinically used for human patients abolishes the killing effects. There are several advantages to using silkworms as an infection model, such as low cost, the absence of ethical problems that are associated with the use of mammals, and a body size large enough to handle while injecting sample solution into the hemolymph. We screened S. aureus mutants with attenuated virulence against silkworms and found three novel virulence regulatory genes, cvfA, cvfB, and cvfC. These genes contribute to virulence against mice and are required for exotoxin production. The cvfA gene is required for expression of the agr locus, which regulates most exotoxin genes, and a novel DNA binding protein SarZ. Silkworms are susceptible to S. aureus beta toxin, P. aeruginosa exotoxin A, and diphtheria toxin. Therefore, silkworms are a promising infection model animal for the identification and evaluation of virulenceassociated genes.

  18. Modeling malaria infected cells in microcirculation

    NASA Astrophysics Data System (ADS)

    Raffiee, Amir Hossein; Dabiri, Sadegh; Motavalizadeh Ardekani, Arezoo

    2016-11-01

    Plasmodim (P.) falciparum is one of the deadliest types of malaria species that invades healthy red blood cells (RBC) in human blood flow. This parasite develops through 48-hour intra-RBC process leading to significant morphological and mechanical (e.g., stiffening) changes in RBC membrane. These changes have remarkable effects on blood circulation such as increase in flow resistance and obstruction in microcirculation. In this work a computational framework is developed to model RBC suspension in blood flow using front-tracking technique. The present study focuses on blood flow behavior under normal and infected circumstances and predicts changes in blood rheology for different levels of parasitemia and hematocrit. This model allows better understanding of blood flow circulation up to a single cell level and provides us with realistic and deep insight into hematologic diseases such as malaria.

  19. Aeromonas hydrophila Sepsis Mimicking Vibrio vulnificus Infection.

    PubMed

    Park, Se Young; Nam, Hyun Min; Park, Kun; Park, Seok Don

    2011-09-01

    Aeromonas hydrophila is a facultatively anaerobic, asporogenous gram-negative rod that has often been regarded as an opportunistic pathogen in hosts with impairment of a local or general defense mechanism. A 68-year-old alcoholic woman presented with shock and gangrene on the right arm. At first, her clinical presentations were severe painful erythematous swelling that worsened within a few hours with development of gangrene, edema, and blisters. Bullous fluid and blood cultures yielded A. hydrophila. Histopathological findings of sections obtained from the vesicle revealed subepidermal vesicles; necrosis of the epidermis, papillary dermis, and subcutaneous fat; and massive hemorrhage in the subcutis. Despite all efforts to save the patient, she died 8 hours after admission. Clinical features of A. hydrophila sepsis resemble those of Vibrio vulnificus sepsis. Therefore, in addition to the case report, we compared the cultural, biochemical, and morphological differences between A. hydrophila and V. vulnificus for facilitation of early and accurate identification of the causative agent.

  20. Henipavirus infections: lessons from animal models.

    PubMed

    Dhondt, Kévin P; Horvat, Branka

    2013-04-09

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

  1. Henipavirus Infections: Lessons from Animal Models

    PubMed Central

    Dhondt, Kévin P.; Horvat, Branka

    2013-01-01

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

  2. A lung segmental model of chronic Pseudomonas infection in sheep.

    PubMed

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

    2013-01-01

    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. 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 (>10(4) cfu/g). 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.

  3. Xanthogranulomatous cholecystitis mimicking gallbladder cancer.

    PubMed

    Ewelukwa, Ofor; Ali, Omair; Akram, Salma

    2014-05-08

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

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

    PubMed

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

    2007-09-01

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

  5. [Geostatistical modeling of Ascaris lumbricoides infection].

    PubMed

    Fortes, Bruno de Paula Menezes Drumond; Ortiz Valencia, Luis Iván; Ribeiro, Simone do Vale; Medronho, Roberto de Andrade

    2004-01-01

    The following study intends to model the spatial distribution of ascariasis, through the use of geoprocessing and geostatistic analysis. The database used in the study was taken from the PAISQUA project, including a coproparasitologic and domiciliary survey, conducted in 19 selected census tracts of Rio de Janeiro State, Brazil, randomly selecting a group of 1,550 children aged 1 to 9 years old plotting them in their respective domicile's centroids. Risk maps of Ascaris lumbricoides were generated by indicator kriging. The estimated and observed values from the cross-validation were compared using a ROC curve. An isotropic spherical semivariogram model with a range of 30m and nugget effect of 50% was employed in ordinary indicator kriging to create a map of probability of A. lumbricoides infection. The area under the ROC curve indicated a significant global accuracy. The occurrence of disease could be estimated in the study area, and a risk map was elaborated through the use ordinary kriging. The spatial statistics analysis has proven itself adequate for predicting the occurrence of ascariasis, unrestricted to the regions political boundaries.

  6. Humanized chimeric mouse models of hepatitis B virus infection.

    PubMed

    Sun, Suwan; Li, Jun

    2017-06-01

    Hepatitis B virus (HBV) infection is associated with an increased risk of hepatic cirrhosis, hepatocellular carcinoma, fulminant hepatitis and end-stage hepatic failure. Despite the availability of anti-HBV therapies, HBV infection remains a major global public health problem. Developing an ideal animal model of HBV infection to clarify the details of the HBV replication process, the viral life cycle, the resulting immunoresponse and the precise pathogenesis of HBV is difficult because HBV has an extremely narrow host range and almost exclusively infects humans. In this review, we summarize and evaluate animal models available for studying HBV infection, especially focusing on humanized chimeric mouse models, and we discuss future development trends regarding immunocompetent humanized mouse models that can delineate the natural history and immunopathophysiology of HBV infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Mouse Models for Campylobacter jejuni Colonization and Infection.

    PubMed

    Stahl, Martin; Graef, Franziska A; Vallance, Bruce A

    2017-01-01

    Relevant animal models for Campylobacter jejuni infection have been difficult to establish due to C. jejuni's inability to cause disease in many common animal research models. Fortunately, recent work has proven successful in developing several new and relevant mouse models of C. jejuni infection, including the SIGIRR-deficient mouse strain that develops acute enterocolitis in response to C. jejuni. Here we describe how to properly infect mice with C. jejuni, as well as a number of accompanying histological techniques to aid in studying C. jejuni colonization and infection in mice.

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

    PubMed Central

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

    2012-01-01

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

  9. A Model for HCMV Infection in Immunosuppressed Patients

    PubMed Central

    Kepler, G.M.; Banks, H.T.; Davidian, M.; Rosenberg, E.S.

    2009-01-01

    We propose a model for HCMV infection in healthy and immunosuppressed patients. First, we present the biological model and formulate a system of ordinary differential equations to describe the pathogenesis of primary HCMV infection in immunocompetent and immunosuppressed individuals. We then investigate how clinical data can be applied to this model. Approximate parameter values for the model are derived from data available in the literature and from mathematical and physiological considerations. Simulations with the approximated parameter values demonstrates that the model is capable of describing primary, latent, and secondary (reactivated) HCMV infection. Reactivation simulations with this model provide a window into the dynamics of HCMV infection in (D-R+) transplant situations, where latently-infected recipients (R+) receive transplant tissue from HCMV-naive donors (D-). PMID:20161307

  10. In vivo efficacy of apramycin in murine infection models.

    PubMed

    Meyer, Martin; Freihofer, Pietro; Scherman, Michael; Teague, Joanne; Lenaerts, Anne; Böttger, Erik C

    2014-11-01

    Apramycin is a unique aminoglycoside with a dissociation of antibacterial activity and ototoxicity. We assessed the antibacterial efficacy of apramycin in two murine models of infection, Mycobacterium tuberculosis aerosol infection and Staphylococcus aureus septicemia. In both infection models, the efficacy of apramycin was comparable to that of amikacin. These results suggest that apramycin has the potential to become a clinically useful agent against drug-resistant pathogens and support further development of this promising unique aminoglycoside.

  11. 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.

  12. Missed Appendicitis: Mimicking Urologic Symptoms

    PubMed Central

    Akhavizadegan, Hamed

    2012-01-01

    Appendicitis, a common disease, has different presentations. This has made its diagnosis difficult. This paper aims to present two cases of missed appendicitis with completely urologic presentation and the way that helped us to reach the correct diagnosis. The first case with symptoms fully related to kidney and the second mimicking epididymorchitis hindered prompt diagnosis. Right site of the pain, relapsing fever, frequent physical examination, and resistance to medical treatment were main clues which help us to make correct diagnosis. PMID:23326748

  13. Animal models of henipavirus infection: a review.

    PubMed

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

    2009-09-01

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

  14. 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.

  15. Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism

    PubMed Central

    Dacheux, Denis; Biteau, Nicolas; Miezan, Benjamin; Van Reet, Nick; Carrington, Mark; Doua, Felix; Baltz, Théo

    2009-01-01

    major clinical symptoms despite an early dissemination and growth of the parasites in different organs including the CNS, as demonstrated by bioluminescent imaging. Conclusions/Significance Whereas trypanosome characterisation assigned all these isolates to the homogeneous Group I of T. b. gambiense, they clearly induce very different infections in mice thus mimicking the broad clinical diversity observed in HAT due to T. b. gambiense. Therefore, these murine models will be very useful for the understanding of different aspects of the physiopathology of HAT and for the development of new diagnostic tools and drugs. PMID:19721701

  16. 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

  17. Stability of differential susceptibility and infectivity epidemic models

    PubMed Central

    Bonzi, B.; Fall, A. A.; Iggidr, Abderrahman; Sallet, Gauthier

    2011-01-01

    We introduce classes of differential susceptibility and infectivity epidemic models. These models address the problem of flows between the different susceptible, infectious and infected compartments and differential death rates as well. We prove the global stability of the disease free equilibrium when the basic reproduction ratio ≤ 1 and the existence and uniqueness of an endemic equilibrium when > 1. We also prove the global asymptotic stability of the endemic equilibrium for a differential susceptibility and staged progression infectivity model, when > 1. Our results encompass and generalize those of [18, 22]. AMS Subject Classification : 34A34,34D23,34D40,92D30 PMID:20148330

  18. 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

  19. Iliacus pyomyositis mimicking septic arthritis of the hip joint.

    PubMed

    Chen W-S; Wan Y-L

    1996-01-01

    The iliacus muscle is closely associated with the psoas muscle, femoral nerve, hip joint, pelvic and intraabdominal structures; thus, its disorders may present as lower abdominal pain, hip pain, or femoral neuropathy. Iliacus pyomyositis, a primary bacterial infection of the skeletal muscle not secondary to a contiguous skin, bone, or soft-tissue infection, presenting as hip pain, femoral neuropathy, and sympathetic effusion of the hip joint in an 8-year-old boy mimicked septic arthritis of the hip joint. Computed tomography was helpful in delineating the accurate location of the lesion. Surgical drainage and appropriate antibiotic therapy led to complete resolution and full functional recovery.

  20. 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.

  1. HPV-16 infection and cervical cancer: modeling the influence of duration of infection and precancerous lesions.

    PubMed

    Baussano, Iacopo; Ronco, Guglielmo; Segnan, Nereo; French, Katherine; Vineis, Paolo; Garnett, Geoff P

    2010-03-01

    The patterns of transmission, clearance, and progression of HPV infection and the related precancerous lesions are key to accurately model cervical cancer epidemiology and prevention. We have developed an age-structured dynamic model of the transmission of HPV-16 infection. This mathematical model accounts, for the first time, for the effect of infection and precancerous lesions duration on the natural history of HPV-16 infection and precancerous lesions. The model's output has been fitted to contemporaneous sets of data from Turin, Italy, to estimate parameters that have had been indirectly tested by comparing them with other estimates reported in the literature. The average probability of HPV-16 infection transmission per sexual partnership was about 40%. The HPV-16 clearance and progression rates decreased as the length of time with infection increased, clearance ranging between 1.6 per woman-year (in the first 6 months of infection) and 0.036 (after more than 6 years of infection), and progression between 0.072 and 0.018 per woman-year. The rate of clearance of precancerous lesions (CIN2+) was inversely dependent on age, while the progression of CIN2+ toward invasive cervical cancer increased as the precancerous lesions persisted. The present study also suggests that an exclusive role of women's age in shaping the rate of progression to cancer is unlikely. These results should inform future analyses. Including more accurately the role of the duration of infection and precancerous lesions as determinants of the cervical cancer occurrence in models of cervical cancer control may influence predictors of the effectiveness of intervention strategies.

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

    PubMed Central

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

    2015-01-01

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

  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. Megakaryocytes mimicking metastatic breast carcinoma.

    PubMed

    Hoda, Syed A; Resetkova, Erika; Yusuf, Yasmin; Cahan, Anthony; Rosen, Paul P

    2002-05-01

    False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.

  5. Norwegian scabies mimicking rupioid psoriasis*

    PubMed Central

    Costa, Juliana Bastos; de Sousa, Virna Lygia Lobo Rocha; da Trindade Neto, Pedro Bezerra; Paulo Filho, Thomás de Aquino; Cabral, Virgínia Célia Dias Florêncio; Pinheiro, Patrícia Moura Rossiter

    2012-01-01

    Norwegian scabies is a highly contagious skin infestation caused by an ectoparasite, Scarcoptes scabiei var. Hominis, which mainly affects immunosuppressed individuals. Clinically, it may simulate various dermatoses such as psoriasis, Darier's disease, seborrheic dermatitis, among others. This is a case report of a 33-year-old woman, immunocompetent, diagnosed with generalized anxiety disorder (cancer phobia), who had erythematous, well-defined plaques, covered with rupioid crusts, on her neck, axillary folds, breast, periumbilical region, groin area, besides upper back and elbows, mimicking an extremely rare variant of psoriasis, denominated rupioid psoriasis. PMID:23197214

  6. Tinea capitis mimicking folliculitis decalvans.

    PubMed

    Tangjaturonrusamee, C; Piraccini, B M; Vincenzi, C; Starace, M; Tosti, A

    2011-01-01

    We report on an adult patient with tinea capitis caused by Microsporum canis, who presented with diffuse alopecia and follicular pustules, mimicking folliculitis decalvans. Examination of the scalp showed severe alopecia with prominent involvement of the frontal and vertex scalp: the skin was markedly erythematous with pustules and brownish crusts. Videodermoscopy revealed visible follicular ostia, numerous pustular lesions and several comma hairs. Fluconazole 150 mg a week for 8 weeks associated with ketoconazole shampoo cleared the inflammatory lesions and produced complete hair regrowth. © 2009 Blackwell Verlag GmbH.

  7. The great mimickers of rosacea.

    PubMed

    Olazagasti, Jeannette; Lynch, Peter; Fazel, Nasim

    2014-07-01

    Although rosacea is one of the most common conditions treated by dermatologists, it also is one of the most misunderstood. It is a chronic disorder affecting the central parts of the face and is characterized by frequent flushing; persistent erythema (ie, lasting for at least 3 months); telangiectasia; and interspersed episodes of inflammation with swelling, papules, and pustules. Understanding the clinical variants and disease course of rosacea is important to differentiate this entity from other conditions that can mimic rosacea. Herein we present several mimickers of rosacea that physicians should consider when diagnosing this condition.

  8. Splenic inflammatory pseudotumor mimicking angiosarcoma.

    PubMed

    Hsu, Chao-Wen; Lin, Chieh-Hsin; Yang, Tsung-Lung; Chang, Hong-Tai

    2008-11-07

    Splenic tumors are rare. Differentiation of the tumors before operation is of great value regarding the outcome. A case of a 32-year-old man with a splenic inflammatory pseudotumor (IPT) mimicking splenic angiosarcoma is described. The tumor was highly suspected of being splenic angiosarcoma based on radiological findings preoperatively. However, after splenectomy, histopathological examinations revealed splenic IPT. Splenic IPT and angiosarcoma are rare and often pose diagnostic difficulties because the clinical and radiological findings are obscure. Due to large differences in prognosis, we briefly reviewed the clinical, radiological, and pathological features of both of the tumors.

  9. Splenic inflammatory pseudotumor mimicking angiosarcoma

    PubMed Central

    Hsu, Chao-Wen; Lin, Chieh-Hsin; Yang, Tsung-Lung; Chang, Hong-Tai

    2008-01-01

    Splenic tumors are rare. Differentiation of the tumors before operation is of great value regarding the outcome. A case of a 32-year-old man with a splenic inflammatory pseudotumor (IPT) mimicking splenic angiosarcoma is described. The tumor was highly suspected of being splenic angiosarcoma based on radiological findings preoperatively. However, after splenectomy, histopathological examinations revealed splenic IPT. Splenic IPT and angiosarcoma are rare and often pose diagnostic difficulties because the clinical and radiological findings are obscure. Due to large differences in prognosis, we briefly reviewed the clinical, radiological, and pathological features of both of the tumors. PMID:19009664

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

    PubMed Central

    Pilloux, Ludovic; LeRoy, Didier; Brunel, Christophe

    2016-01-01

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

  11. Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease.

    PubMed Central

    Brieland, J.; Freeman, P.; Kunkel, R.; Chrisp, C.; Hurley, M.; Fantone, J.; Engleberg, C.

    1994-01-01

    The role of host immune responses in the pathogenesis of Legionnaires' disease is incompletely understood, due in part to the current lack of an animal model that is both susceptible to replicative Legionella pneumophila-induced lung infection and for which species-specific immunological reagents are available. We have developed a model of replicative L. pneumophila lung infection in intratracheally inoculated A/J mice. L. pneumophila was obtained in the exponential growth phase and inoculated into the trachea of 6- to 8-week-old female A/J mice. Microbiological and histopathological evidence of infection was demonstrated in mice inoculated with 10(6) colony-forming units. Development of an acute pneumonia that resembled human Legionnaires' disease coincided with exponential growth of the bacteria in the lung 24 to 48 hours after intratracheal inoculation of L. pneumophila. This was associated with increased plasma levels of interferon-gamma at 24 hours after inoculation. After 48 hours, the bacteria were gradually eliminated from the lung over the next 5 days, corresponding with resolution of the inflammatory response in the lung, thereby mimicking the outcome frequently seen in the immunocompetent human host. Treatment of animals with anti-interferon-gamma antibody enhanced bacterial replication and disease progression, indicating an important role of host immune response in resolution of the infection. Because of the availability of murine-specific reagents, this model of replicative L. pneumophila lung infection in A/J mice after intrapulmonary inoculation of L. pneumophila potentially provides an important tool for future studies investigating the role of host immune responses in the pathogenesis of Legionnaires' disease in the immunocompetent host. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:7992856

  12. 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.

  13. Experimental models of bone and prosthetic joint infections.

    PubMed

    Crémieux, A C; Carbon, C

    1997-12-01

    Bone and joint infections are difficult to cure. The difficulty is related to the presence of bacteria adherent to foreign material in many cases and also to the limited activity of antibiotics in infected bones. Clinical trials are difficult to design because of the heterogeneity of the disease and the number of factors that could influence the therapeutic response. To control for these multiple variables, attempts have been made to develop reliable animal models of osteomyelitis and prosthetic joint infections that closely mimic the different infections seen in orthopedic surgery and that allow evaluation of the efficacy of surgical procedures as well as local or systemic antibiotic therapy. These models will continue to provide us information on the pathogenesis and management of such infections.

  14. Mathematical modelling: a tool for hospital infection control.

    PubMed

    Grundmann, H; Hellriegel, B

    2006-01-01

    Health-care-associated infections caused by antibiotic-resistant pathogens have become a menace in hospitals worldwide and infection control measures have lead to vastly different outcomes in different countries. During the past 6 years, a theoretical framework based on mathematical models has emerged that provides solid and testable hypotheses and opens the road to a quantitative assessment of the main obstructions that undermine current efforts to control the spread of health-care-associated infections in hospitals and communities. We aim to explain to a broader audience of professionals in health care, infection control, and health systems administration some of these models that can improve the understanding of the hidden dynamics of health-care-associated infections. We also appraise their usefulness and limitations as an innovative research and decision tool for control purposes.

  15. Disease transmission model for community-associated Clostridium difficile infection.

    PubMed

    Otten, A M; Reid-Smith, R J; Fazil, A; Weese, J S

    2010-06-01

    Participating researchers and public health personnel at a Canadian workshop in 2007, noted considerable gaps in current understanding of community-associated Clostridium difficile infection (CA-CDI), specifically infection sources and risk factors. A disease transmission model for CA-CDI was requested as an initial step towards a risk assessment, to analyse infection sources and risk factors, addressing priority research areas. The developed model contains eight infection states (susceptible, gastrointestinal exposure, colonized, diseased, deceased, clinically resolved colonized, relapse diseased, and cleared) and notes directional transfers between the states. Most published research used focused on hospital-associated C. difficile infection (HA-CDI) and further studies are needed to substantiate the use of HA-CDI knowledge in the transmission of CA-CDI. The aim was to provide a consistent framework for researchers, and provide a theoretical basis for future quantitative risk assessment of CA-CDI.

  16. 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.

  17. 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.

  18. The Chimpanzee Model for Hepatitis B Virus Infection

    PubMed Central

    Wieland, Stefan F.

    2015-01-01

    Even before the discovery of hepatitis B virus (HBV), it was known that chimpanzees (Pan troglodytes) are susceptible to human hepatitis viruses. The chimpanzee is the only primate animal model for HBV infections. Much like HBV-infected human patients, chimpanzees can develop acute and chronic HBV infections and consequent hepatitis. Chimpanzees also develop a cellular immune response similar to that observed in humans. For these reasons, the chimpanzee has proven to be an invaluable model for investigations on HBV-driven disease pathogenesis and also the testing of novel antiviral therapies and prophylactic approaches. PMID:26033082

  19. Modeling Innate Immune Response to Early Mycobacterium Infection

    PubMed Central

    Carvalho, Rafael V.; Kleijn, Jetty; Meijer, Annemarie H.

    2012-01-01

    In the study of complex patterns in biology, mathematical and computational models are emerging as important tools. In addition to experimental approaches, these modeling tools have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to mycobacterial infection and tuberculous granuloma formation. We present an approach in which a computational model represents the interaction of the Mycobacterium infection with the innate immune system in zebrafish at a high level of abstraction. We use the Petri Net formalism to model the interaction between the key host elements involved in granuloma formation and infection dissemination. We define a qualitative model for the understanding and description of causal relations in this dynamic process. Complex processes involving cell-cell or cell-bacteria communication can be modeled at smaller scales and incorporated hierarchically into this main model; these are to be included in later elaborations. With the infection mechanism being defined on a higher level, lower-level processes influencing the host-pathogen interaction can be identified, modeled, and tested both quantitatively and qualitatively. This systems biology framework incorporates modeling to generate and test hypotheses, to perform virtual experiments, and to make experimentally verifiable predictions. Thereby it supports the unraveling of the mechanisms of tuberculosis infection. PMID:23365620

  20. New swine model of infected soft tissue blast injury.

    PubMed

    Li, Jinqing; Topaz, Morris; Xun, Wenxing; Li, Wangzhou; Wang, Xiaolin; Liu, Haibo; Yuan, Yanqin; Chen, Shaozong; Li, Yuejun; Li, Xueyong

    2012-10-01

    War injuries, especially blast injuries, have a high risk of infection. However, no animal models of infected war injuries have been built in large animals, which retards both the understanding and the treatment optimization of infected war injuries. Soft tissue blast injuries were created by explosion of electric detonators in white domestic pigs. The ultra structure of the tissue around the wound was determined by transmission electron microscope. To develop infection of blast injury wounds, the pigs were housed in a standard animal house which was disinfected periodically, and the wounds were left untreated for 3 days. Wound specimens were collected daily to determine the bacterial load and bacterial components. To determine whether infection induces tissue necrosis in infected soft tissue blast injury wounds, uninfected blast injury wounds were created as controls of infected wounds by surgical debridement daily, and the wound area and wound depth of both wounds were measured. The wound area and the wound depth of the soft tissue blast injury created in this study fell in the range of human moderate soft tissue war injuries, and the ultra structure of the wounds was comparable with that of human blast injury wounds. The bacterial load of uninfected wounds was under 10 colony forming unit/g during the first 3 days of injury, while that of infected wounds was over 10 colony forming unit/g after 2 days of injury. The infected soft tissue blast injury wounds contained most of the bacteria frequently isolated in battlefield wounds. In addition, infection induced evident tissue necrosis in infected blast injury wounds. The infected soft tissue blast injury wounds mimic those in human, and they can be used to address key points of treatment optimization.

  1. Inverse heat mimicking of given objects

    NASA Astrophysics Data System (ADS)

    Alwakil, Ahmed; Zerrad, Myriam; Bellieud, Michel; Amra, Claude

    2017-03-01

    We address a general inverse mimicking problem in heat conduction. The objects to cloak and mimic are chosen beforehand; these objects identify a specific set of space transformations. The shapes that can be mimicked are derived from the conductivity matrices. Numerical calculation confirms all of the analytical predictions. The technique provides key advantages for applications and can be extended to the field of waves.

  2. Challenging mimickers of primary systemic vasculitis.

    PubMed

    Miloslavsky, Eli M; Stone, John H; Unizony, Sebastian H

    2015-01-01

    The need to distinguish true primary systemic vasculitis from its multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, antiphospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease.

  3. Cryptosporidium Infection Risk: Results of New Dose-Response Modeling.

    PubMed

    Messner, Michael J; Berger, Philip

    2016-10-01

    Cryptosporidium human dose-response data from seven species/isolates are used to investigate six models of varying complexity that estimate infection probability as a function of dose. Previous models attempt to explicitly account for virulence differences among C. parvum isolates, using three or six species/isolates. Four (two new) models assume species/isolate differences are insignificant and three of these (all but exponential) allow for variable human susceptibility. These three human-focused models (fractional Poisson, exponential with immunity and beta-Poisson) are relatively simple yet fit the data significantly better than the more complex isolate-focused models. Among these three, the one-parameter fractional Poisson model is the simplest but assumes that all Cryptosporidium oocysts used in the studies were capable of initiating infection. The exponential with immunity model does not require such an assumption and includes the fractional Poisson as a special case. The fractional Poisson model is an upper bound of the exponential with immunity model and applies when all oocysts are capable of initiating infection. The beta Poisson model does not allow an immune human subpopulation; thus infection probability approaches 100% as dose becomes huge. All three of these models predict significantly (>10x) greater risk at the low doses that consumers might receive if exposed through drinking water or other environmental exposure (e.g., 72% vs. 4% infection probability for a one oocyst dose) than previously predicted. This new insight into Cryptosporidium risk suggests additional inactivation and removal via treatment may be needed to meet any specified risk target, such as a suggested 10(-4) annual risk of Cryptosporidium infection.

  4. Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

    PubMed

    Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

    2012-01-01

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

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

    PubMed

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

    2014-10-01

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

  6. 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

  7. 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. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For

  8. Pediatric myositis ossificans mimicking osteosarcoma.

    PubMed

    Yamaga, Kensaku; Kobayashi, Eisuke; Kubota, Daisuke; Setsu, Nokitaka; Tanaka, Yuya; Minami, Yusuke; Tanzawa, Yoshikazu; Nakatani, Fumihiko; Kawai, Akira; Chuman, Hirokazu

    2015-10-01

    Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11-year-old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill-defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages. © 2015 Japan Pediatric Society.

  9. Diseases mimicking intussusception: diagnostic dilemma.

    PubMed

    Karakus, Suleyman Cuneyt; Ozokutan, Bulent Hayri; Ceylan, Haluk

    2014-10-01

    Intussusception is a common abdominal emergency in early childhood. The aim of this study was to describe the diseases mimicking intussusception and to discuss the causes and management of these conditions. Seven patients who were initially diagnosed as having intussusception on abdominal ultrasonography but who had a final diagnosis of diseases other than intussusception were reviewed retrospectively. Two patients with ileocolic intussusception underwent ultrasonography-guided reduction with a hydrostatic method but the ultrasonographic findings persisted. At surgery, only edematous ileocecal valve and mesenteric lymphadenopathy were observed. In three patients with Henoch-Schönlein purpura, initial abdominal ultrasonography showed intussusception. The patients with no sign of obstructive symptoms were managed conservatively with a diagnosis of intramural hemorrhage and on follow up the ultrasonographic findings of intussusception was resolved. One patient with the target sign on computed tomography and ultrasonography of the abdomen underwent ileocolic resection and end-to-end anastomosis due to a tumor in the cecum. There was no evidence of intussusception. One patient with a cyst in the right lower quadrant accompanying intussusception on ultrasonography of the abdomen underwent ultrasonography-guided reduction but the ultrasonographic findings persisted. On exploration, only cecal duplication cyst without intussusception was detected. Cecal resection including the cyst and end-to-end ileocolic anastomosis were performed. Ultrasonography, color Doppler ultrasonography, barium or hydrostatic enema and computed tomography are helpful in diagnosing intussusception, but patients with radiologic findings of intussusception should be evaluated on symptoms and clinical findings before surgical intervention. Also, other diseases mimicking intussusception should be kept in mind in the differential diagnosis. © 2014 Japan Pediatric Society.

  10. Murine Mycobacterium marinum Infection as a Model for Tuberculosis.

    PubMed

    Lienard, Julia; Carlsson, Fredric

    2017-01-01

    Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial-and particularly Mycobacterium tuberculosis-virulence strategies and pathogenesis is of great importance. To this end several in vivo infection models are available (Guirado and Schlesinger, Front Immunol 4:98, 2013; Leung et al., Eur J Immunol 43:2246-2254, 2013; Patel et al., J Lab Physicians 3:75-79, 2011; van Leeuwen et al., Cold Spring Harb Perspect Med 5:a018580, 2015). While these models all have their merits they also exhibit limitations, and none perfectly mimics all aspects of human tuberculosis. Thus, there is a need for multiple models that may complement each other, ultimately allowing us to gain true insight into the pathogenesis of mycobacterial infections.Here, we describe a recently developed mouse model of Mycobacterium marinum infection that allows kinetic and quantitative studies of disease progression in live animals [8]. Notably, this model exhibits features of human tuberculosis not replicated in M. tuberculosis infected mice, and may provide an important complement to the field. For example, granulomas in the M. marinum model develop central caseating necrosis (Carlsson et al., PLoS Pathog 6:e1000895, 2010), a hallmark of granulomas in human tuberculosis normally not replicated in murine M. tuberculosis infection. Moreover, while tuberculosis is heterogeneous and presents with a continuum of active and latent disease, M. tuberculosis infected mice essentially lack this dynamic range and do not replicate latency (Guirado and Schlesinger, Front Immunol 4:98, 2013

  11. 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

  12. Generation and Analysis of Humanized Mouse Model of EBV Infection.

    PubMed

    Imadome, Ken-Ichi; Fujiwara, Shigeyoshi

    2017-01-01

    The recent development of severely immunodeficient mouse strains enabled the production of new-generation humanized mice, in which major components of the human immune system are reconstituted. These new-generation humanized mice can be infected with human pathogenic viruses that do not infect regular mice and target cells of the hematoimmune system. Here we describe the method for preparing humanized mice, infecting them with EBV, and for their virological and immunological analyses. The results obtained from our own mouse models are briefly described.

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

    PubMed

    Rockx, Barry

    2014-07-01

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

  14. 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

  15. [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.

  16. Embryonated chicken eggs: An experimental model for Pythium insidiosum infection.

    PubMed

    Verdi, Camila M; Jesus, Francielli P K; Kommers, Glaucia; Ledur, Pauline C; Azevedo, Maria I; Loreto, Erico S; Tondolo, Juliana S M; Andrade, Eduardo N C; Schlemmer, Karine B; Alves, Sydney H; Santurio, Janio M

    2017-10-03

    Pythiosis is a severe disease caused by Pythium insidiosum. Currently, the research on the treatment of pythiosis uses rabbits as an experimental infection model. To reduce the use of animals in scientific experimentation, alternative models are increasingly necessary options. The objective of this study was to establish a new experimental infection model for pythiosis using embryonated chicken eggs. First, we tested the inoculation of 4 zoospore concentrations into the egg allantoic cavity at 3 embryonic days. We observed that increased zoospore concentration causes a decrease in survival time, and at a later embryonic day (the 14th) of infection, embryos showed delayed mortality. To confirm the reproducibility of the model, we chose the 14th embryonic day for the inoculation of 50 zoospores/egg, and the experiment was repeated twice. Mortality began with 30% embryos 48 hours after inoculation, and 95% embryos died within 72 hours. There was no mortality in the uninfected control group. The infection was confirmed by culture, PCR and histopathology. Immunohistochemistry confirmed the presence of hyphae in blood vessels in the umbilical cords in 95% of embryos and only 1 liver (5%). Our results suggest that embryonated eggs can be a very useful alternative infection model to study pythiosis. © 2017 Blackwell Verlag GmbH.

  17. Development of mouse models for analysis of human virus infections.

    PubMed

    Takaki, Hiromi; Oshiumi, Hiroyuki; Shingai, Masashi; Matsumoto, Misako; Seya, Tsukasa

    2017-04-01

    Viruses usually exhibit strict species-specificity as a result of co-evolution with the host. Thus, in mouse models, a great barrier exists for analysis of infections with human-tropic viruses. Mouse models are unlikely to faithfully reproduce the human immune response to viruses or viral compounds and it is difficult to evaluate human therapeutic efficacy with antiviral reagents in mouse models. Humans and mice essentially have different immune systems, which makes it difficult to extrapolate mouse results to humans. In addition, apart from immunological reasons, viruses causing human diseases do not always infect mice because of species tropism. One way to determine tropism would be a virus receptor that is expressed on affected cells. The development of gene-disrupted mice and Tg mice, which express human receptor genes, enables us to analyze several viral infections in mice. Mice are, indeed, susceptible to human viruses when artificially infected in receptor-supplemented mice. Although the mouse cells less efficiently permit viral replication than do human cells, the models for analysis of human viruses have been established in vivo as well as in vitro, and explain viral pathogenesis in the mouse systems. In most systems, however, nucleic acid sensors and type I interferon suppress viral propagation to block the appearance of infectious manifestation. We herein review recent insight into in vivo antiviral responses induced in mouse infection models for typical human viruses. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  18. An Immunocompromised Murine Model of Chronic Bartonella Infection

    PubMed Central

    Chiaraviglio, Lucius; Duong, Scott; Brown, Daniel A.; Birtles, Richard J.; Kirby, James E.

    2010-01-01

    Bartonella are ubiquitous Gram-negative pathogens that cause chronic blood stream infections in mammals. Two species most often responsible for human infection, B. henselae and B. quintana, cause prolonged febrile illness in immunocompetent hosts, known as cat scratch disease and trench fever, respectively. Fascinatingly, in immunocompromised hosts, these organisms also induce new blood vessel formation leading to the formation of angioproliferative tumors, a disease process named bacillary angiomatosis. In addition, they cause an endothelial-lined cystic disease in the liver known as bacillary peliosis. Unfortunately, there are as yet no completely satisfying small animal models for exploring these unique human pathologies, as neither species appears able to sustain infection in small animal models. Therefore, we investigated the potential use of other Bartonella species for their ability to recapitulate human pathologies in an immunodeficient murine host. Here, we demonstrate the ability of Bartonella taylorii to cause chronic infection in SCID/BEIGE mice. In this model, Bartonella grows in extracellular aggregates, embedded within collagen matrix, similar to previous observations in cat scratch disease, bacillary peliosis, and bacillary angiomatosis. Interestingly, despite overwhelming infection later in disease, evidence for significant intracellular replication in endothelial or other cell types was not evident. We believe that this new model will provide an important new tool for investigation of Bartonella–host interaction. PMID:20395436

  19. Multiscale model for pedestrian and infection dynamics during air travel

    NASA Astrophysics Data System (ADS)

    Namilae, Sirish; Derjany, Pierrot; Mubayi, Anuj; Scotch, Mathew; Srinivasan, Ashok

    2017-05-01

    In this paper we develop a multiscale model combining social-force-based pedestrian movement with a population level stochastic infection transmission dynamics framework. The model is then applied to study the infection transmission within airplanes and the transmission of the Ebola virus through casual contacts. Drastic limitations on air-travel during epidemics, such as during the 2014 Ebola outbreak in West Africa, carry considerable economic and human costs. We use the computational model to evaluate the effects of passenger movement within airplanes and air-travel policies on the geospatial spread of infectious diseases. We find that boarding policy by an airline is more critical for infection propagation compared to deplaning policy. Enplaning in two sections resulted in fewer infections than the currently followed strategy with multiple zones. In addition, we found that small commercial airplanes are better than larger ones at reducing the number of new infections in a flight. Aggregated results indicate that passenger movement strategies and airplane size predicted through these network models can have significant impact on an event like the 2014 Ebola epidemic. The methodology developed here is generic and can be readily modified to incorporate the impact from the outbreak of other directly transmitted infectious diseases.

  20. Modeling rotavirus infection and antiviral therapy using primary intestinal organoids.

    PubMed

    Yin, Yuebang; Bijvelds, Marcel; Dang, Wen; Xu, Lei; van der Eijk, Annemiek A; Knipping, Karen; Tuysuz, Nesrin; Dekkers, Johanna F; Wang, Yijin; de Jonge, Jeroen; Sprengers, Dave; van der Laan, Luc J W; Beekman, Jeffrey M; Ten Berge, Derk; Metselaar, Herold J; de Jonge, Hugo; Koopmans, Marion P G; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-11-01

    Despite the introduction of oral vaccines, rotavirus still kills over 450,000 children under five years of age annually. The absence of specific treatment prompts research aiming at further understanding of pathogenesis and the development of effective antiviral therapy, which in turn requires advanced experimental models. Given the intrinsic limitations of the classical rotavirus models using immortalized cell lines infected with laboratory-adapted strains in two dimensional cultures, our study aimed to model infection and antiviral therapy of both experimental and patient-derived rotavirus strains using three dimensional cultures of primary intestinal organoids. Intestinal epithelial organoids were successfully cultured from mouse or human gut tissues. These organoids recapitulate essential features of the in vivo tissue architecture, and are susceptible to rotavirus. Human organoids are more permissive to rotavirus infection, displaying an over 10,000-fold increase in genomic RNA following 24h of viral replication. Furthermore, infected organoids are capable of producing infectious rotavirus particles. Treatment of interferon-alpha or ribavirin inhibited viral replication in organoids of both species. Importantly, human organoids efficiently support the infection of patient-derived rotavirus strains and can be potentially harnessed for personalized evaluation of the efficacy of antiviral medications. Therefore, organoids provide a robust model system for studying rotavirus-host interactions and assessing antiviral medications.

  1. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Animal models and the molecular biology of hepadnavirus infection.

    PubMed

    Mason, William S

    2015-04-01

    Australian antigen, the envelope protein of hepatitis B virus (HBV), was discovered in 1967 as a prevalent serum antigen in hepatitis B patients. Early electron microscopy (EM) studies showed that this antigen was present in 22-nm particles in patient sera, which were believed to be incomplete virus. Complete virus, much less abundant than the 22-nm particles, was finally visualized in 1970. HBV was soon found to infect chimpanzees, gorillas, orangutans, gibbon apes, and, more recently, tree shrews (Tupaia belangeri) and cynomolgus macaques (Macaca fascicularis). This restricted host range placed limits on the kinds of studies that might be performed to better understand the biology and molecular biology of HBV and to develop antiviral therapies to treat chronic infections. About 10 years after the discovery of HBV, this problem was bypassed with the discovery of viruses related to HBV in woodchucks, ground squirrels, and ducks. Although unlikely animal models, their use revealed the key steps in hepadnavirus replication and in the host response to infection, including the fact that the viral nuclear episome is the ultimate target for immune clearance of transient infections and antiviral therapy of chronic infections. Studies with these and other animal models have also suggested interesting clues into the link between chronic HBV infection and hepatocellular carcinoma. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. 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.

  6. 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

  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. Basic stochastic models for viral infection within a host.

    PubMed

    Vidurupola, Sukhitha W; Allen, Linda J S

    2012-10-01

    Stochastic differential equation (SDE) models are formulated for intra-host virus-cell dynamics during the early stages of viral infection, prior to activation of the immune system. The SDE models incorporate more realism into the mechanisms for viral entry and release than ordinary differential equation (ODE) models and show distinct differences from the ODE models. The variability in the SDE models depends on the concentration, with much greater variability for small concentrations than large concentrations. In addition, the SDE models show significant variability in the timing of the viral peak. The viral peak is earlier for viruses that are released from infected cells via bursting rather than via budding from the cell membrane.

  9. Tracking vaginal, anal and oral infection in a mouse papillomavirus infection model

    PubMed Central

    Budgeon, Lynn R.; Cladel, Nancy M.; Balogh, Karla; Myers, Roland; Cooper, Timothy K.

    2015-01-01

    Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral presence could be identified and quantified by collecting lavage samples from cervicovaginal, anal and oral sites. Nude mice infected at these sites with infectious MmuPV1 were tracked for up to 23 weeks starting at 6 weeks post-infection. Viral DNA copy number was determined by SYBR Green Q-PCR analysis. In addition, we tracked viral DNA load through three complete oestrous cycles to pinpoint whether there was a correlation between the DNA load and the four stages of the oestrous cycle. Our results showed that high viral DNA copy number was reproducibly detected from both anal and cervicovaginal lavage samples. The infection and disease progression were further confirmed by histology, cytology, in situ hybridization, immunohistochemistry and transmission electron microscopy. Interestingly, the viral copy number fluctuated over the oestrous cycle, with the highest level at the oestrus stage, implying that multiple sampling might be necessary to provide a reliable diagnosis. Virus DNA was detected in oral lavage samples at a later time after infection. Lower viral DNA load was found in oral samples when compared with those in anal and vaginal tracts. To our knowledge, our study is the first in vivo study to sequentially monitor papillomavirus infection from mucosal anal, oral and vaginal tracts in a preclinical model. PMID:26399579

  10. Stochastic spatial structured model for vertically and horizontally transmitted infection

    NASA Astrophysics Data System (ADS)

    Silva, Ana T. C.; Assis, Vladimir R. V.; Pinho, Suani T. R.; Tomé, Tânia; de Oliveira, Mário J.

    2017-02-01

    We study a space structured stochastic model for vertical and horizontal transmitted infection. By means of simple and pair mean-field approximation as well as Monte Carlo simulations, we construct the phase diagram, which displays four states: healthy (H), infected (I), extinct (E), and coexistent (C). In state H only healthy hosts are present, whereas in state I only infected hosts are present. The state E is characterized by the extinction of the hosts whereas in state C there is a coexistence of infected and healthy hosts. In addition to the usual scenario with continuous transition between the I, C and H phases, we found a different scenario with the suppression of the C phase and a discontinuous phase transition between I and H phases.

  11. Infections

    MedlinePlus

    ... Eye Infections Pinkeye (Conjunctivitis) Styes Fungal Infections (Ringworm, Yeast, etc.) Diaper Rash Infections That Pets Carry Oral ... Pneumonia Tinea (Ringworm, Jock Itch, Athlete's Foot) Vaginal Yeast Infections Immunizations Do My Kids Need Vaccines Before ...

  12. A micro-epidemic model for primary dengue infection

    NASA Astrophysics Data System (ADS)

    Mishra, Arti; Gakkhar, Sunita

    2017-06-01

    In this paper, a micro-epidemic non-linear dynamical model has been proposed and analyzed for primary dengue infection. The model incorporates the effects of T cells immune response as well as humoral response during pathogenesis of dengue infection. The time delay has been accounted for production of antibodies from B cells. The basic reproduction number (R0) has been computed. Three equilibrium states are obtained. The existence and stability conditions for infection-free and ineffective cellular immune response state have been discussed. The conditions for existence of endemic state have been obtained. Further, the parametric region is obtained where system exhibits complex behavior. The threshold value of time delay has been computed which is critical for change in stability of endemic state. A threshold level for antibodies production rate has been obtained over which the infection will die out even though R0 > 1. The model is in line with the clinical observation that viral load decreases within 7-14 days from the onset of primary infection.

  13. 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.

  14. A guinea pig model of Zika virus infection.

    PubMed

    Kumar, Mukesh; Krause, Keeton K; Azouz, Francine; Nakano, Eileen; Nerurkar, Vivek R

    2017-04-11

    Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV. Dunkin-Hartley guinea pigs were inoculated with 10(6) plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay. Upon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs. The guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.

  15. A Murine Model for Escherichia coli Urinary Tract Infection

    PubMed Central

    Hannan, Thomas J.; Hunstad, David A.

    2015-01-01

    Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI. PMID:26468108

  16. A Murine Model for Escherichia coli Urinary Tract Infection.

    PubMed

    Hannan, Thomas J; Hunstad, David A

    2016-01-01

    Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

  17. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Modelling Co-Infection with Malaria and Lymphatic Filariasis

    PubMed Central

    Slater, Hannah C.; Gambhir, Manoj; Parham, Paul E.; Michael, Edwin

    2013-01-01

    Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R0 of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings. PMID:23785271

  19. Modelling co-infection with malaria and lymphatic filariasis.

    PubMed

    Slater, Hannah C; Gambhir, Manoj; Parham, Paul E; Michael, Edwin

    2013-01-01

    Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R₀ of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings.

  20. 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.

  1. 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.

  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. PMID:27594885

  3. 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.

  4. 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

  5. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

    PubMed Central

    2017-01-01

    ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. PMID:28148798

  6. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    PubMed

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

  7. Inverse heat mimicking of given objects

    PubMed Central

    Alwakil, Ahmed; Zerrad, Myriam; Bellieud, Michel; Amra, Claude

    2017-01-01

    We address a general inverse mimicking problem in heat conduction. The objects to cloak and mimic are chosen beforehand; these objects identify a specific set of space transformations. The shapes that can be mimicked are derived from the conductivity matrices. Numerical calculation confirms all of the analytical predictions. The technique provides key advantages for applications and can be extended to the field of waves. PMID:28252031

  8. Epidemic extinction in a generalized susceptible-infected-susceptible model

    NASA Astrophysics Data System (ADS)

    Chen, Hanshuang; Huang, Feng; Zhang, Haifeng; Li, Guofeng

    2017-01-01

    We study the extinction of epidemics in a generalized susceptible-infected-susceptible model, where a susceptible individual becomes infected at the rate λ when contacting m infective individual(s) simultaneously, and an infected individual spontaneously recovers at the rate μ. By employing the Wentzel-Kramers-Brillouin approximation for the master equation, the problem is reduced to finding the zero-energy trajectories in an effective Hamiltonian system, and the mean extinction time < T> depends exponentially on the associated action S and the size of the population N, < T> ˜ \\exp ≤ft(NS\\right) . Because of qualitatively different bifurcation features for m  =  1 and m≥slant 2 , we derive independently the expressions of S as a function of the rescaled infection rate λ /μ . For the weak infection, S scales to the distance to the bifurcation with an exponent 2 for m  =  1 and 3/2 for m≥slant 2 . Finally, a rare-event simulation method is used to validate the theory.

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

    PubMed Central

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

    1989-01-01

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

  10. Takeover times for a simple model of network infection

    NASA Astrophysics Data System (ADS)

    Ottino-Löffler, Bertrand; Scott, Jacob G.; Strogatz, Steven H.

    2017-07-01

    We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps T does it take to completely infect a network of N nodes, starting from a single infected node? An analogy to the classic "coupon collector" problem of probability theory reveals that the takeover time T is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for N ≫1 , the takeover time T is distributed as a Gumbel distribution for the star graph, as the convolution of two Gumbel distributions for a complete graph and an Erdős-Rényi random graph, as a normal for a one-dimensional ring and a two-dimensional lattice, and as a family of intermediate skewed distributions for d -dimensional lattices with d ≥3 (these distributions approach the convolution of two Gumbel distributions as d approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed.

  11. Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

    PubMed

    Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2015-10-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p < .0001). We offer proof that H. pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

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

    PubMed Central

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

    2015-01-01

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

  13. Murine model of cutaneous infection with Streptococcus pyogenes.

    PubMed

    Medina, Eva

    2010-01-01

    Despite the medical advances achieved during the last century to fight against bacteria, viruses, fungi and parasites, infectious diseases are still a major cause of death, disability, and social and economic upheaval for millions around the world. Challenges remain in countering microorganisms even where antibiotics and vaccines are available. Much remains to be learned about basic aspects of the host-pathogen relationship and the complexity of the immune response to infection. Animal models represent a powerful tool to dissect the host response to infection, as well as the pathogenesis of the microbe. One of the advantages of using animal models is that both genetic and environmental factors that may influence the course of an infection can be controlled, allowing a precise cause-effect analysis of the host-pathogen interactions. In addition, there are no real alternatives to whole animal models in the study of integrative physiology and dynamic pathophysiologic alterations. The use of animal models has also proven invaluable for testing the efficacy of experimental antimicrobial agents and their therapeutic regimes. The mouse model is the most widely used for many reasons, including its cost effectiveness, the high number of immunological reagents available for this species, and the relative ease of biocontainment. Mouse strains with specific properties such as transgenic mouse strains with gene insertion or targeted mutation (knock-out) are very effective tools for studying the role of specific genes controlling the immune response to infectious pathogens. Murine models will remain the most appropriate tool for evaluating new therapeutic strategies for the treatment of various diseases. The closer the model is adapted to the human disease, the more reliable will be the results.In this chapter, the experimental procedures required to establish a mouse model of cutaneous and soft tissue infection are detailed. This model has provided invaluable insights into the

  14. Mouse Model of Neurological Complications Resulting from Encephalitic Alphavirus Infection.

    PubMed

    Ronca, Shannon E; Smith, Jeanon; Koma, Takaaki; Miller, Magda M; Yun, Nadezhda; Dineley, Kelly T; Paessler, Slobodan

    2017-01-01

    Long-term neurological complications, termed sequelae, can result from viral encephalitis, which are not well understood. In human survivors, alphavirus encephalitis can cause severe neurobehavioral changes, in the most extreme cases, a schizophrenic-like syndrome. In the present study, we aimed to adapt an animal model of alphavirus infection survival to study the development of these long-term neurological complications. Upon low-dose infection of wild-type C57B/6 mice, asymptomatic and symptomatic groups were established and compared to mock-infected mice to measure general health and baseline neurological function, including the acoustic startle response and prepulse inhibition paradigm. Prepulse inhibition is a robust operational measure of sensorimotor gating, a fundamental form of information processing. Deficits in prepulse inhibition manifest as the inability to filter out extraneous sensory stimuli. Sensory gating is disrupted in schizophrenia and other mental disorders, as well as neurodegenerative diseases. Symptomatic mice developed deficits in prepulse inhibition that lasted through 6 months post infection; these deficits were absent in asymptomatic or mock-infected groups. Accompanying prepulse inhibition deficits, symptomatic animals exhibited thalamus damage as visualized with H&E staining, as well as increased GFAP expression in the posterior complex of the thalamus and dentate gyrus of the hippocampus. These histological changes and increased GFAP expression were absent in the asymptomatic and mock-infected animals, indicating that glial scarring could have contributed to the prepulse inhibition phenotype observed in the symptomatic animals. This model provides a tool to test mechanisms of and treatments for the neurological sequelae of viral encephalitis and begins to delineate potential explanations for the development of such sequelae post infection.

  15. Mouse Model of Neurological Complications Resulting from Encephalitic Alphavirus Infection

    PubMed Central

    Ronca, Shannon E.; Smith, Jeanon; Koma, Takaaki; Miller, Magda M.; Yun, Nadezhda; Dineley, Kelly T.; Paessler, Slobodan

    2017-01-01

    Long-term neurological complications, termed sequelae, can result from viral encephalitis, which are not well understood. In human survivors, alphavirus encephalitis can cause severe neurobehavioral changes, in the most extreme cases, a schizophrenic-like syndrome. In the present study, we aimed to adapt an animal model of alphavirus infection survival to study the development of these long-term neurological complications. Upon low-dose infection of wild-type C57B/6 mice, asymptomatic and symptomatic groups were established and compared to mock-infected mice to measure general health and baseline neurological function, including the acoustic startle response and prepulse inhibition paradigm. Prepulse inhibition is a robust operational measure of sensorimotor gating, a fundamental form of information processing. Deficits in prepulse inhibition manifest as the inability to filter out extraneous sensory stimuli. Sensory gating is disrupted in schizophrenia and other mental disorders, as well as neurodegenerative diseases. Symptomatic mice developed deficits in prepulse inhibition that lasted through 6 months post infection; these deficits were absent in asymptomatic or mock-infected groups. Accompanying prepulse inhibition deficits, symptomatic animals exhibited thalamus damage as visualized with H&E staining, as well as increased GFAP expression in the posterior complex of the thalamus and dentate gyrus of the hippocampus. These histological changes and increased GFAP expression were absent in the asymptomatic and mock-infected animals, indicating that glial scarring could have contributed to the prepulse inhibition phenotype observed in the symptomatic animals. This model provides a tool to test mechanisms of and treatments for the neurological sequelae of viral encephalitis and begins to delineate potential explanations for the development of such sequelae post infection. PMID:28223982

  16. Invasive Trichophyton rubrum mimicking blastomycosis in a patient with solid organ transplant.

    PubMed

    Talebi-Liasi, Faezeh; Shinohara, Michi M

    2017-09-01

    We present a case of tissue invasive Trichophyton rubrum (T. rubrum) histologically mimicking blastomycosis in a patient with kidney transplant on chronic immunosuppression. Invasive dermatophyte infections are rare, and present a diagnostic challenge to the dermatopathologist due to atypical clinical and histopathological presentations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  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. Epidemic models with an infected-infectious period

    NASA Astrophysics Data System (ADS)

    Méndez, Vicenç

    1998-03-01

    The introduction of an infective-infectious period on the geographic spread of epidemics is considered in two different models. The classical evolution equations arising in the literature are generalized and the existence of epidemic wave fronts is revised. The asymptotic speed is obtained and improves previous results for the Black Death plague.

  19. Murine models susceptibility to distinct Trypanosoma cruzi I genotypes infection.

    PubMed

    León, Cielo M; Montilla, Marleny; Vanegas, Ricardo; Castillo, Maria; Parra, Edgar; Ramírez, Juan David

    2017-04-01

    Chagas disease is a complex zoonosis that affects around 8 million people worldwide. This pathology is caused by Trypanosoma cruzi, a kinetoplastid parasite that shows tremendous genetic diversity evinced in six distinct Discrete Typing Units (TcI-TcVI) including a recent genotype named as TcBat and associated with anthropogenic bats. TcI presents a broad geographical distribution and has been associated with chronic cardiomyopathy. Recent phylogenetic studies suggest the existence of two genotypes (Domestic (TcIDom) and sylvatic TcI) within TcI. The understanding of the course of the infection in different mouse models by these two genotypes is not yet known. Therefore, we infected 126 animals (ICR-CD1, National Institute of Health (NIH) and Balb/c) with two TcIDom strains and one sylvatic strain for a follow-up period of 60 days. We quantified the parasitaemia, immune response and histopathology observing that the maximum day of parasitaemia was achieved at day 21 post-infection. Domestic strains showed higher parasitaemia than the sylvatic strain in the three mouse models; however in the survival curves Balb/c mice were less susceptible to infection compared with NIH and ICR-CD1. Our results suggest that the genetic background plays a fundamental role in the natural history of the infection and the sympatric TcI genotypes have relevant implications in disease pathogenesis.

  20. Animal challenge models of henipavirus infection and pathogenesis.

    PubMed

    Geisbert, Thomas W; Feldmann, Heinz; Broder, Christopher C

    2012-01-01

    The henipaviruses, Hendra virus (HeV), and Nipah virus (NiV), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. A number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and African green monkeys have been employed as animal models of human henipavirus infection. Here, we review the development of animal models for henipavirus infection, discuss the pathology and pathogenesis of these models, and assess the utility of each model to recapitulate important aspects of henipavirus-mediated disease seen in humans.

  1. Models for the study of Clostridium difficile infection

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Krag, Thomas O; Vissing, John

    2015-12-01

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

  3. Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection.

    PubMed

    Mateo, Rosa I; Xiao, Shu-Yuan; Lei, Hao; DA Rosa, Amelia P A Travassos; Tesh, Robert B

    2007-04-01

    After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.

  4. 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

  5. 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.

  6. 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

  7. Choosing an appropriate infection model to study quorum sensing inhibition in Pseudomonas infections.

    PubMed

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

    2013-09-23

    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.

  8. A Cellular Automata Model of Infection Control on Medical Implants.

    PubMed

    Prieto-Langarica, Alicia; Kojouharov, Hristo; Chen-Charpentier, Benito; Tang, Liping

    2011-06-01

    S. epidermidis infections on medically implanted devices are a common problem in modern medicine due to the abundance of the bacteria. Once inside the body, S. epidermidis gather in communities called biofilms and can become extremely hard to eradicate, causing the patient serious complications. We simulate the complex S. epidermidis-Neutrophils interactions in order to determine the optimum conditions for the immune system to be able to contain the infection and avoid implant rejection. Our cellular automata model can also be used as a tool for determining the optimal amount of antibiotics for combating biofilm formation on medical implants.

  9. 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

  10. Experimental Models of Ocular Infection with Toxoplasma Gondii.

    PubMed

    Dukaczewska, Agata; Tedesco, Roberto; Liesenfeld, Oliver

    2015-12-01

    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.

  11. Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

    PubMed Central

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

    2014-01-01

    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. PMID:25183731

  12. 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

  13. 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.

  14. Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment

    PubMed Central

    Domínguez-Hüttinger, Elisa; Boon, Neville J.; Clarke, Thomas B.; Tanaka, Reiko J.

    2017-01-01

    Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We

  15. Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment.

    PubMed

    Domínguez-Hüttinger, Elisa; Boon, Neville J; Clarke, Thomas B; Tanaka, Reiko J

    2017-01-01

    Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We

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

    PubMed

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

    2012-12-01

    The microbial stability of intermediate moisture foods (IMF) is linked with the possible growth of osmophilic yeast and xerophilic moulds. As most of these products have a long shelf life the assessment of the microbial stability is often an important hurdle in product innovation. In this study a screening of several Zygosaccharomyces rouxii strains towards individual stress factors was performed and growth/no growth models were developed, incorporating a(w), pH, acetic acid and ethanol concentrations. These stress factors are important for sweet IMF such as chocolate fillings, ganache, marzipan, etc. A comparison was made between a logistic regression model with and without the incorporation of time as an explanatory variable. Next to the model development, a screening of the effect of chemical preservatives (sorbate and benzoate) was performed, in combination with relevant stress factors within the experimental design of the model. The results of the study showed that the influence of the investigated environmental stress factors on the growth/no growth boundary of Z. rouxii is the most significant in the first 30-40 days of incubation. Incorporating time as an explanatory variable in the model had the advantage that the growth/no growth boundary could be predicted at each time between 0 and 60 days of incubation at 22 °C. However, the growth/no growth boundary enlarged significantly leading to a less accurate prediction on the growth probability of Z. rouxii. The developed models can be a useful tool for product developers of sweet IMF. Screening with chemical preservatives revealed that benzoic acid was much less active towards Z. rouxii than sorbic acid or a mixture of both acids. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

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

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

    PubMed

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

    2012-05-21

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

  19. Modelling the transmission of healthcare associated infections: a systematic review

    PubMed Central

    2013-01-01

    Background Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. Methods MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. Results In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. Conclusions Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and

  20. Modelling the transmission of healthcare associated infections: a systematic review.

    PubMed

    van Kleef, Esther; Robotham, Julie V; Jit, Mark; Deeny, Sarah R; Edmunds, William J

    2013-06-28

    Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries.The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model

  1. In the hunt for therapeutic targets: mimicking the growth, metastasis, and stromal associations of early-stage lung cancer using a novel orthotopic animal model.

    PubMed

    Weiss, Ido D; Ella, Ezra; Dominsky, Omri; Smith, Yoav; Abraham, Michal; Wald, Hanna; Shlomai, Zippora; Zamir, Gideon; Feigelson, Sara W; Shezen, Elias; Bar-Shai, Amir; Alon, Ronen; Izhar, Uzi; Peled, Amnon; Shapira, Oz M; Wald, Ori

    2015-01-01

    The existing shortage of animal models that properly mimic the progression of early-stage human lung cancer from a solitary confined tumor to an invasive metastatic disease hinders accurate characterization of key interactions between lung cancer cells and their stroma. We herein describe a novel orthotopic animal model that addresses these concerns and consequently serves as an attractive platform to study tumor-stromal cell interactions under conditions that reflect early-stage lung cancer. Unlike previous methodologies, we directly injected small numbers of human or murine lung cancer cells into murine's left lung and longitudinally monitored disease progression. Next, we used green fluorescent protein-tagged tumor cells and immuno-fluorescent staining to determine the tumor's microanatomic distribution and to look for tumor-infiltrating immune cells and stromal cells. Finally, we compared chemokine gene expression patterns in the tumor and lung microenvironment. We successfully generated a solitary pulmonary nodule surrounded by normal lung parenchyma that grew locally and spread distally over time. Notably, we found that both fibroblasts and leukocytes are recruited to the tumor's margins and that distinct myeloid cell attracting and CCR2-binding chemokines are specifically induced in the tumor microenvironment. Our orthotopic lung cancer model closely mimics the pathologic sequence of events that characterizes early-stage human lung cancer propagation. It further introduces new means to monitor tumor-stromal cell interactions and offers unique opportunities to test therapeutic targets under conditions that reflect early-stage lung cancer. We argue that for such purposes our model is superior to lung cancer models that are based either on genetic induction of epithelial transformation or on ectopic transplantation of malignant cells.

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

    PubMed Central

    Pabst, Breana; Pitts, Betsey; Lauchnor, Ellen

    2016-01-01

    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

  3. 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

  4. 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.

  5. Hendra and nipah infection: pathology, models and potential therapies.

    PubMed

    Vigant, Frederic; Lee, Benhur

    2011-06-01

    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.

  6. Dynamics of a stochastic HIV-1 infection model with logistic growth

    NASA Astrophysics Data System (ADS)

    Jiang, Daqing; Liu, Qun; Shi, Ningzhong; Hayat, Tasawar; Alsaedi, Ahmed; Xia, Peiyan

    2017-03-01

    This paper is concerned with a stochastic HIV-1 infection model with logistic growth. Firstly, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HIV-1 infection model. Then we obtain sufficient conditions for extinction of the infection. The stationary distribution shows that the infection can become persistent in vivo.

  7. 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

  8. 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

  9. 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. © 2015 AlphaMed Press.

  10. Infection

    DTIC Science & Technology

    2010-09-01

    standing, diagnosis, and treatment of musculoskeletal infections. Key Words: musculoskeletal infection, biofilm , bacteria, biomaterial (J Orthop Trauma...form a biofilm , or slime layer.1 The recurrence of infections is often the result of microbial biofilm formation on the implant, enabling the persistence...Klebsiella pneumoniae). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm

  11. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Mathematical modeling of citrus groves infected by huanglongbing.

    PubMed

    Jacobsen, Karly; Stupiansky, Jillian; Pilyugin, Sergei S

    2013-06-01

    Huanglongbing (citrus greening) is a bacterial disease that is significantly impacting the citrus industry in Florida and poses a risk to the remaining citrus-producing regions of the United States. A mathematical model of a grove infected by citrus greening is developed. An equilibrium stability analysis is presented. The basic reproductive number and its relation to the persistence of the disease is discussed. A numerical study is performed to illustrate the theoretical findings.

  14. Mimicking acceleration in the constant-bang-time Lemaître-Tolman model: Shell crossings, density distributions, and light cones

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-09-01

    The Lemaître-Tolman model with Λ=0 and constant bang time that imitates the luminosity distance-redshift relation of the ΛCDM model using the energy function E alone contains shell crossings. In this paper, the location in spacetime and the consequences of existence of the shell-crossing set (SCS) are investigated. The SCS would come into view of the central observer only at t ≈1064T to the future from now, where T is the present age of the Universe, but would not leave any recognizable trace in her observations. Light rays emitted near to the SCS are blueshifted at the initial points, but the blueshift is finite, and is overcompensated by later-induced redshifts if the observer is sufficiently far. The local blueshifts cause that z along a light ray is not a monotonic function of the comoving radial coordinate r. As a consequence, the angular diameter distance DA and the luminosity distance DL from the central observer fail to be functions of z; the relations DA(z) and DL(z) are multiple-valued in a vicinity of the SCS. The following quantities are calculated and displayed: (1) The distribution of mass density on a few characteristic hypersurfaces of constant time; some of them intersect the SCS. (2) The distribution of density along the past light cone of the present central observer. (3) A few light cones intersecting the SCS at characteristic instants. (4) The redshift profiles along several light cones. (5) The extremum-redshift hypersurface. (6) The DA(z) and DL(z) relations. (7) The last scattering time and its comparison with the ΛCDM last scattering epoch.

  15. 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

  16. 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

  17. 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.

  18. Pleuropulmonary paragonimiasis: mimicker of tuberculosis

    PubMed Central

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

    2013-01-01

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

  19. Recurrent epiploic appendagitis mimicking appendicitis and cholecystitis

    PubMed Central

    Hearne, Christopher B.; Taboada, Jorge

    2017-01-01

    Epiploic appendagitis (EA) is a rare cause of acute abdominal pain caused by inflammation of an epiploic appendage. It has a nonspecific clinical presentation that may mimic other acute abdominal pathologies on physical exam, such as appendicitis, diverticulitis, or cholecystitis. However, EA is usually benign and self-limiting and can be treated conservatively. We present the case of a patient with two episodes of EA, the first mimicking acute appendicitis and the second mimicking acute cholecystitis. Although recurrence of EA is rare, it should be part of the differential diagnosis of acute, localized abdominal pain. A correct diagnosis of EA will prevent unnecessary hospitalization, antibiotic use, and surgical procedures. PMID:28127129

  20. Tissue mimicking materials for dental ultrasound

    PubMed Central

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

    2008-01-01

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

  1. Tissue mimicking materials for dental ultrasound.

    PubMed

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

    2008-04-01

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

  2. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Mimicking the oxygen minimum zones: stimulating interaction of aerobic archaeal and anaerobic bacterial ammonia oxidizers in a laboratory-scale model system

    PubMed Central

    Yan, Jia; Haaijer, Suzanne C M; Op den Camp, Huub J M; Niftrik, Laura; Stahl, David A; Könneke, Martin; Rush, Darci; Sinninghe Damsté, Jaap S; Hu, Yong Y; Jetten, Mike S M

    2012-01-01

    In marine oxygen minimum zones (OMZs), ammonia-oxidizing archaea (AOA) rather than marine ammonia-oxidizing bacteria (AOB) may provide nitrite to anaerobic ammonium-oxidizing (anammox) bacteria. Here we demonstrate the cooperation between marine anammox bacteria and nitrifiers in a laboratory-scale model system under oxygen limitation. A bioreactor containing ‘Candidatus Scalindua profunda’ marine anammox bacteria was supplemented with AOA (Nitrosopumilus maritimus strain SCM1) cells and limited amounts of oxygen. In this way a stable mixed culture of AOA, and anammox bacteria was established within 200 days while also a substantial amount of endogenous AOB were enriched. ‘Ca. Scalindua profunda’ and putative AOB and AOA morphologies were visualized by transmission electron microscopy and a C18 anammox [3]-ladderane fatty acid was highly abundant in the oxygen-limited culture. The rapid oxygen consumption by AOA and AOB ensured that anammox activity was not affected. High expression of AOA, AOB and anammox genes encoding for ammonium transport proteins was observed, likely caused by the increased competition for ammonium. The competition between AOA and AOB was found to be strongly related to the residual ammonium concentration based on amoA gene copy numbers. The abundance of archaeal amoA copy numbers increased markedly when the ammonium concentration was below 30 μM finally resulting in almost equal abundance of AOA and AOB amoA copy numbers. Massive parallel sequencing of mRNA and activity analyses further corroborated equal abundance of AOA and AOB. PTIO addition, inhibiting AOA activity, was employed to determine the relative contribution of AOB versus AOA to ammonium oxidation. The present study provides the first direct evidence for cooperation of archaeal ammonia oxidation with anammox bacteria by provision of nitrite and consumption of oxygen. PMID:23057688

  4. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Animal models of respiratory syncytial virus infection and disease.

    PubMed

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

    2015-08-01

    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.

  6. 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

  7. Modeling the impact of Trichomonas vaginalis infection on HIV transmission in HIV-infected individuals in medical care

    PubMed Central

    Quinlivan, E. Byrd; Patel, Shilpa N.; Grodensky, Catherine A.; Golin, Carol E.; Tien, Hsiao-Chuan; Hobbs, Marcia M.

    2012-01-01

    Background To assess factors associated with having a Trichomonas vaginalis (TV) infection among persons receiving care for HIV and estimate the number of transmitted HIV infections attributable to TV. Methods HIV clinic patients were recruited from two secondary prevention studies, screened by urine nucleic-acid amplification tests for sexually transmitted infections (STIs) and interviewed about risk factors (baseline, 6 and 12 months). We conducted mathematical modeling of the results to estimate the number of transmitted HIV infections attributable to TV among a cohort of HIV-infected patients receiving medical care in North Carolina. Results TV was prevalent in 7.4%, and incident in 2% – 3% of subjects at follow-up. Individuals with HIV RNA less than 400 copies/ml (OR 0.32, 95% CI: 0.14 – 0.73) and at least 13 years of education (OR 0.24, 95% CI: 0.08 –0.70) were less likely to have TV. Mathematical modeling predicted that 0.062 HIV transmission events occur per 100 HIV infected women in the absence of TV infection and 0.076 HIV infections per 100 HIV and TV-infected women (estimate range: 0.070 – 0.079), indicating that 23% of the HIV transmission events from HIV-infected women may be attributable to TV infection when 22% of women are co-infected with TV. Conclusions The data suggest the need for improved diagnosis of TV infection and suggest that HIV-infected women in medical care may be appropriate targets for enhanced testing and treatment. PMID:22902662

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

    PubMed Central

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

    2004-01-01

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

  9. Animal Models of Chikungunya Virus Infection and Disease.

    PubMed

    Haese, Nicole N; Broeckel, Rebecca M; Hawman, David W; Heise, Mark T; Morrison, Thomas E; Streblow, Daniel N

    2016-12-15

    Chikungunya virus (CHIKV) is a reemerging alphavirus that causes acute febrile illness and severe joint pain in humans. Although acute symptoms often resolve within a few days, chronic joint and muscle pain can be long lasting. In the last decade, CHIKV has caused widespread outbreaks of unprecedented scale in the Americas, Asia, and the Indian Ocean island regions. Despite these outbreaks and the continued expansion of CHIKV into new areas, mechanisms of chikungunya pathogenesis and disease are not well understood. Experimental animal models are indispensable to the field of CHIKV research. The most commonly used experimental animal models of CHIKV infection are mice and nonhuman primates; each model has its advantages for studying different aspects of CHIKV disease. This review will provide an overview of animal models used to study CHIKV infection and disease and major advances in our understanding of chikungunya obtained from studies performed in these models. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    SciTech Connect

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

    1984-01-01

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

  11. 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. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2014-01-01

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

  13. Development of a Zika Virus Infection Model in Cynomolgus Macaques

    PubMed Central

    Koide, Fusataka; Goebel, Scott; Snyder, Beth; Walters, Kevin B.; Gast, Alison; Hagelin, Kimberly; Kalkeri, Raj; Rayner, Jonathan

    2016-01-01

    Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva, and urine) and tissues (testes and brain) were assessed for viral load by quantitative reverse transcription polymerase chain reaction and neutralizing antibodies (Nab) by 50% Plaque Reduction Neutralization Test (PRNT50) at various times post-infection (p.i). PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2–3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 × 103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates. PMID:28066354

  14. A gastrointestinal rotavirus infection mouse model for immune modulation studies

    PubMed Central

    2011-01-01

    Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection. Methods BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured. Results Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected. Conclusions Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection. PMID:21385425

  15. Immune quiescence: a model of protection against HIV infection.

    PubMed

    Card, Catherine M; Ball, Terry Blake; Fowke, Keith R

    2013-11-20

    Aberrant immune activation is a strong correlate of HIV disease progression, but little is known about how immune activation alters susceptibility to HIV infection. Susceptibility to HIV infection varies between individuals, but the immunological determinants of HIV transmission are not well understood. Here, we present evidence from studies of HIV transmission in the context of clinical trials and HIV-exposed seronegative (HESN) cohorts that implicates elevated immune activation as a risk factor for acquiring HIV. We propose a model of protection from infection based on a phenotype of low baseline immune activation referred to as immune quiescence. Immune quiescence is evidenced by reduced expression of T cell activation markers, low levels of generalized gene transcription and low levels of proinflammatory cytokine and chemokine production in the periphery and genital mucosa of HESN. Since HIV preferentially replicates in activated CD4+ T cells, immune quiescence may protect against infection by limiting HIV target cell availability. Although the determinants of immune quiescence are unclear, several potential factors have been identified that may be involved in driving this phenotype. HESN were shown to have elevated proportions of regulatory T cells (Tregs), which are known to suppress T cell activation. Likewise, proteins involved in controlling inflammation in the genital tract have been found to be elevated in HESN. Furthermore, expression of interferon regulatory factor 1 (IRF-1) is reduced in HESN as a consequence of genetic polymorphisms and differential epigenetic regulation. Since IRF-1 is an important regulator of immune responses, it may play a role in maintaining immune quiescence. Based on this model, we propose a novel avenue for HIV prevention targeted based on reducing host mucosal immune activation.

  16. 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

  17. Systemic sarcoidosis mimicking malignant metastatic disease

    PubMed Central

    Hammen, Irena; Sherson, David Lee; Davidsen, Jesper Roemhild

    2015-01-01

    We present a case of systemic sarcoidosis involving the liver, pancreas, lungs, mediastinal and intraabdominal lymph nodes and bones. Multiple organ system manifestations mimicked malignant metastatic disease. The diagnosis was established with clinical, radiological, and pathological findings after neoplasm was ruled out by pathological tests. The patient showed rapid symptom remission with systemic steroid treatment. PMID:26672956

  18. Lymphomatoid granulomatosis mimicking interstitial lung disease.

    PubMed

    Braham, Emna; Ayadi-Kaddour, Aïda; Smati, Belhassen; Ben Mrad, Sonia; Besbes, Mohammed; El Mezni, Faouzi

    2008-11-01

    Lymphoid granulomatosis is a rare form of pulmonary angiitis. This case report presents a patient with lymphoid granulomatosis in whom the clinical presentation, radiological features and the partial response to corticosteroid therapy mimicked interstitial lung disease. Lymphoid granulomatosis was only diagnosed at post-mortem examination. The range of reported clinical presentations, diagnostic approaches and outcomes are described.

  19. The Plaque-Antiserum Method: an Assay of Virus Infectivity and an Experimental Model of Virus Infection

    PubMed Central

    De Flora, Silvio

    1974-01-01

    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. Images PMID:4364462

  20. 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.

  1. Animal models for Ebola and Marburg virus infections

    PubMed Central

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

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

  2. 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.

  3. 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

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

    PubMed

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

    2015-12-10

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

  5. Pathogenesis of Candida albicans Infections in the Alternative Chorio-Allantoic Membrane Chicken Embryo Model Resembles Systemic Murine Infections

    PubMed Central

    Jacobsen, Ilse D.; Große, Katharina; Berndt, Angela; Hube, Bernhard

    2011-01-01

    Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM) and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite its limitations, it

  6. Mexican immigrants' explanatory model of latent tuberculosis infection.

    PubMed

    McEwen, Marylyn M

    2005-10-01

    This article reveals how the multiple and disparate explanations of latent tuberculosis infection (LTBI) from the U.S. and Mexico professional health sectors and the popular sector are used to inform the explanatory model (EM) of LTBI for Mexican immigrants residing in the U.S.-Mexico border region. Fourteen immigrants, nine diagnosed with LTBI (n = 9) and their spouses (n = 5) participated in this critical ethnographic study. Because care seeking and treatment decisions are influenced by EMs, the results indicate that it is imperative that interventions for Mexican immigrants with LTBI are built on an understanding of their illness experience and are contextually meaningful.

  7. Multiple models of porcine teschovirus pathogenesis in endemically infected pigs.

    PubMed

    Chiu, Shu-Chun; Yang, Chih-Lin; Chen, Ya-Mei; Hu, Shu-Chia; Chiu, Kuo-Chao; Lin, Yi-Chien; Chang, Chia-Yi; Wang, Fun-In

    2014-01-10

    Porcine teschoviruses (PTVs) belong to the genus Teschovirus within the family Picornaviridae. PTVs are universal contaminants in pig herds in endemic and multi-infection status. To further the understanding of PTV pathogenesis in endemically infected pigs, a set of samples was studied by real time reverse transcription PCR (qRT-PCR) to quantitate viral loads in tissues and by in situ hybridization (ISH) to locate PTV signals in target cells, both targeting the 5'-NTR. cRNA of PTV-1 and PTV-7, in vitro transcribed from cloned fragments of 5'-NTR of 2 viruses, was used to construct standard curves and to run parallel in qRT-PCR, which had detection limits of 10(1) copies/per reaction, with a linearity in between 10(1) and 10(7) copies/per reaction and correlation coefficients of 0.997-0.9988. The qRT-PCR specifically amplified RNA from PTV-1 to -11, while excluding those of Sapelovirus, PEV-9 and PEV-10. Inguinal lymph node (LN) had the highest viral load of all (assuming 100%), followed by ileac LN (89-91%), tonsil (66-68%), ileum (59-60%), spleen (38-40%), and kidney (30-31%), with the least in brain (22.9%) of the inguinal LN. The 22.9% load in brain was higher than that anticipated from a simple fecal-oral-viremia operative model. The results suggested in addition that intranasal infection and retrograding axonal infection from the tonsils were equally operative and significant. ISH revealed PTV signals in a wider variety of tissue cell types than before. PTV signals were noted most impressively in neurons of the cerebral cortex and hippocampus and in the dark zone of the germinal center and adjacent paracortex of regional LN. Multiple operative models indicated that PTVs seemed to have no difficulty invading the brain. The key to whether encephalitis would ensue resided in the animal's immune status and topographic differences of neurons' susceptibilities to PTVs. When common co-infected agents are present, as is typical in the field, PTVs may synergize in

  8. Isolated angiitis in the hypothalamus mimicking brain tumor.

    PubMed

    Tsutsumi, Satoshi; Ito, Masanori; Yasumoto, Yukimasa; Kaneda, Kazuhiko

    2008-01-01

    A 64-year-old female presented with exaggerating somnolence without contributory medical and lifestyle histories. She was not aware of any preceding infection or headache. Cerebral magnetic resonance imaging demonstrated an isolated enhanced mass in the hypothalamus without meningeal enhancement. Blood and cerebrospinal fluid examinations showed no significant findings except for hypernatremia and hyperprolactinemia. She underwent an open biopsy via the interhemispheric route. Histological examination revealed marked perivascular lymphocytic aggregation with polyclonal immunostaining both for B and T lymphocytes. No findings suggestive of underlying malignancy were recognized. Extensive work-up aiming at systemic vasculitis and lymphoma revealed no signs of extracranial lesion, so the most probable diagnosis was isolated angiitis in the hypothalamus. Angiitis may originate from the hypothalamus and should be considered in the differential diagnosis of hypothalamic lesion mimicking brain tumor on neuroimaging.

  9. A Rare Presentation of Peritoneal Tuberculosis Mimicking Malignancy

    PubMed Central

    Swe, Thein; Naing, Akari Thein; Phyo, Zaw Win; Thwin, Malar

    2016-01-01

    Our search of literature revealed combined elevations of serum cancer antigen 125 levels and rheumatoid factor levels in a patient with peritoneal tuberculosis has rarely been reported. Thus, we describe the case of a 63-year-old female with large abdominal ascites and malignancy was ruled out with biopsy. High levels of serum cancer antigen and rheumatoid factor were noted. Physicians should be aware that tuberculosis infection could induce elevation of rheumatoid factor levels in the absence of rheumatologic symptoms or disease. A high index of suspicion is required because peritoneal tuberculosis is a great mimicker of other abdominal pathology, especially intraabdominal malignancies and can mislead physicians to undergo unnecessary interventions. PMID:27900335

  10. Oropharyngeal trauma mimicking a first branchial cleft anomaly.

    PubMed

    Larem, Aisha; Sheikh, Rashid; Al Qahtani, Abdulsalam; Khais, Frat; Ganesan, Shanmugam; Haidar, Hassan

    2016-06-01

    We present a unique and challenging case of a remnant foreign body that presented to us in a child disguised as a strongly suspected congenital branchial cleft anomaly. This case entailed oropharyngeal trauma, with a delayed presentation as a retroauricular cyst accompanied by otorrhea that mimicked the classic presentation of an infected first branchial cleft anomaly. During surgical excision of the presumed branchial anomaly, a large wooden stick was found in the tract. The diagnostic and therapeutic obstacles in the management of such cases are highlighted. In addition to exploring the existing literature, we retrospectively analyzed a plausible explanation of the findings of this case. Laryngoscope, 126:E224-E226, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Analysis of Practical Identifiability of a Viral Infection Model

    PubMed Central

    Nguyen, Van Kinh; Klawonn, Frank; Mikolajczyk, Rafael; Hernandez-Vargas, Esteban A.

    2016-01-01

    Mathematical modelling approaches have granted a significant contribution to life sciences and beyond to understand experimental results. However, incomplete and inadequate assessments in parameter estimation practices hamper the parameter reliability, and consequently the insights that ultimately could arise from a mathematical model. To keep the diligent works in modelling biological systems from being mistrusted, potential sources of error must be acknowledged. Employing a popular mathematical model in viral infection research, existing means and practices in parameter estimation are exemplified. Numerical results show that poor experimental data is a main source that can lead to erroneous parameter estimates despite the use of innovative parameter estimation algorithms. Arbitrary choices of initial conditions as well as data asynchrony distort the parameter estimates but are often overlooked in modelling studies. This work stresses the existence of several sources of error buried in reports of modelling biological systems, voicing the need for assessing the sources of error, consolidating efforts in solving the immediate difficulties, and possibly reconsidering the use of mathematical modelling to quantify experimental data. PMID:28036339

  12. Establishment of a superficial skin infection model in mice by using Staphylococcus aureus and Streptococcus pyogenes.

    PubMed

    Kugelberg, Elisabeth; Norström, Tobias; Petersen, Thomas K; Duvold, Tore; Andersson, Dan I; Hughes, Diarmaid

    2005-08-01

    A new animal model for the purpose of studying superficial infections is presented. In this model an infection is established by disruption of the skin barrier by partial removal of the epidermal layer by tape stripping and subsequent application of the pathogens Staphylococcus aureus and Streptococcus pyogenes. The infection and the infection route are purely topical, in contrast to those used in previously described animal models in mice, such as the skin suture-wound model, where the infection is introduced into the deeper layers of the skin. Thus, the present model is considered more biologically relevant for the study of superficial skin infections in mice and humans. Established topical antibiotic treatments are shown to be effective. The procedures involved in the model are simple, a feature that increases throughput and reproducibility. This new model should be applicable to the evaluation of novel antimicrobial treatments of superficial infections caused by S. aureus and S. pyogenes.

  13. 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.

  14. Cutaneous alternariosis microscopically mimicking blastomycosis.

    PubMed

    Osmond, Gregory W; Walters, Robert W; Puri, Puja K

    2011-11-01

    A 57-year-old man status post several myocardial infarcts and heart transplantation presented with a slowly growing violaceous plaque on his lateral left knee at the site of prior minor trauma. A biopsy revealed a suppurative dermatitis with associated pseudocarcinomatous epithelial hyperplasia. There were multiple non-pigmented eosinophilic organisms with clear cytoplasmic halos within the infiltrate. A methenamine silver stain showed round to ovoid organisms of slightly variable size. Rare uni-polar budding, some of which was broad based, was apparent. A few short hyphae with indeterminate septa were also noted. Fontana-Masson, mucicarmine, Alcian blue and Fite stains were all negative. These findings suggested a diagnosis of blastomycosis. However, a fungal culture grew colonies of Alternaria species. Alternariosis has been previously shown to possess morphologic characteristics that can simulate other fungal infections. To our knowledge, a striking similarity to blastomycosis, as seen in our case, has not been previously reported. Dermatopathologists should be aware that alternariosis may mimic blastomycosis, especially when hyphal forms are rare or absent in tissue specimens. Culture is necessary for definitive classification.

  15. Multi-modality gellan gum-based tissue-mimicking phantom with targeted mechanical, electrical, and thermal properties

    NASA Astrophysics Data System (ADS)

    Chen, Roland K.; Shih, A. J.

    2013-08-01

    This study develops a new class of gellan gum-based tissue-mimicking phantom material and a model to predict and control the elastic modulus, thermal conductivity, and electrical conductivity by adjusting the mass fractions of gellan gum, propylene glycol, and sodium chloride, respectively. One of the advantages of gellan gum is its gelling efficiency allowing highly regulable mechanical properties (elastic modulus, toughness, etc). An experiment was performed on 16 gellan gum-based tissue-mimicking phantoms and a regression model was fit to quantitatively predict three material properties (elastic modulus, thermal conductivity, and electrical conductivity) based on the phantom material's composition. Based on these material properties and the regression model developed, tissue-mimicking phantoms of porcine spinal cord and liver were formulated. These gellan gum tissue-mimicking phantoms have the mechanical, thermal, and electrical properties approximately equivalent to those of the spinal cord and the liver.

  16. Mouse model for central nervous system Neospora caninum infections.

    PubMed

    Lindsay, D S; Lenz, S D; Cole, R A; Dubey, J P; Blagburn, B L

    1995-04-01

    Neospora caninum is a protozoan parasite that causes severe disease in transplacentally infected dogs and abortions in domestic ruminants. Rodent models of neosporosis rely on treatment of hosts with methylprednisolone acetate (MPA) to enhance infections. The present study reports the development of an inbred BALB/c mouse model that results in central nervous system neosporosis in the absence of MPA treatment. Seven of 12 BALB/c mice died 26-70 days after subcutaneous (s.c.) inoculation with tachyzoites of the NC-1 strain of N. caninum, and none of 12 BALB/c mice died after s.c. inoculation with tachyzoites of the NC-3 strain. None of 8 HSD:ICR mice (4 mice, NC-1 strain; 4 mice, NC-3 strain) developed clinical neosporosis or died after s.c. inoculation with tachyzoites. Control BALB/c (2) and HSD:ICR (2) mice s.c. inoculated with Hanks' balanced salt solution did not develop clinical signs of disease. Some mice in all N. caninum-inoculated groups had brain lesions, but significantly (P < 0.05) more BALB/c mice inoculated with the NC-1 strain had brain lesions.

  17. Establishment of a novel tick-Babesia experimental infection model

    PubMed Central

    Maeda, Hiroki; Hatta, Takeshi; Alim, M Abdul; Tsubokawa, Daigo; Mikami, Fusako; Matsubayashi, Makoto; Miyoshi, Takeharu; Umemiya-Shirafuji, Rika; Kawazu, Shin-ichiro; Igarashi, Ikuo; Mochizuki, Masami; Tsuji, Naotoshi; Tanaka, Tetsuya

    2016-01-01

    Ticks are potent vectors of many deadly human and animal pathogens. Tick-borne babesiosis is a well-recognized malaria-like disease that occurs worldwide and recently has attracted increased attention as an emerging zoonosis. Although the proliferation of Babesia organisms is essential in the vectors, their detailed lifecycle with time information for migration in ticks remains unknown. A novel study model for the elucidation of the migration speed of Babesia parasites in their vector tick, Haemaphysalis longicornis, has been developed using an artificial feeding system with quantitative PCR method. The detectable DNA of Babesia parasites gradually disappeared in the tick midgut at 1 day post engorgement (DPE), and in contrary increased in other organs. The results indicated that the Babesia parasite passed the H. longicornis midgut within 24 hours post engorgement, migrated to the hemolymph, and then proliferated in the organs except the midgut. This time point may be an important curfew for Babesia parasites to migrate in the tick lumen. We also visualized the Babesia parasites in the experimentally infected ticks and in their eggs using IFAT for detecting their cytoskeletal structure, which suggested the successful tick infection and transovarial transmission of the parasite. This model will shed light on the further understanding of tick-Babesia interactions. PMID:27841321

  18. Mathematical Model for an Effective Management of HIV Infection

    PubMed Central

    Oukouomi Noutchie, Suares Clovis

    2016-01-01

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

  19. A model of Salmonella infection within industrial house hens.

    PubMed

    Prévost, K; Magal, P; Beaumont, C

    2006-10-07

    Salmonella is one of the major sources of toxi-infection in humans. Incidences of human salmonellosis have greatly increased over the past 20 years and this can largely be attributed to epidemics of Salmonella enteritidis phage type 4 within poultry. The main concern with this bacterium is the existence of silent carriers, i.e. animals harbouring S. enteritidis without expressing any visible symptoms. In this article, we formulate a model for S. enteritidis transmission in hen houses, considering both the hens and the environmental bacterium contamination. By considering the hen's individual development of the disease, we build a model for the production of eggs contaminated by S. enteritidis. The objectives are to analyse the dynamic of the disease, and to provide understanding of measures to avoid the endemicity of S. enteritidis in industrial hen houses.

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

    PubMed Central

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

    2014-01-01

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

  1. Occupational Neurobrucellosis Mimicking a Brain Tumor: A Case Report and Review of the Literature

    PubMed Central

    Abdulghani, Dina; Farhan, Roiya; Algahtani, Raghad

    2017-01-01

    Brucellosis is a zoonotic bacterial infection which is transmitted to humans from infected animals and is endemic in many parts of the world including Saudi Arabia. In this article, we report a case of occupational neurobrucellosis that presented with a space-occupying lesion mimicking a brain tumor. We stress on the importance of obtaining detailed social history including occupation to reach the diagnosis in several conditions including brucellosis. We also stress on taking universal precautions when handling any specimens. It may be advisable that manipulation of all unknown specimens arriving at the laboratory should occur in biological safety cabinet until a highly infectious organism is ruled out. Neurobrucellosis should be included in the differential diagnosis in patients presenting with solitary mass lesion mimicking brain tumor especially in endemic areas or high occupational risk group. PMID:28299214

  2. 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

  3. Improving prediction of surgical site infection risk with multilevel modeling.

    PubMed

    Saunders, Lauren; Perennec-Olivier, Marion; Jarno, Pascal; L'Hériteau, François; Venier, Anne-Gaëlle; Simon, Loïc; Giard, Marine; Thiolet, Jean-Michel; Viel, Jean-François

    2014-01-01

    Surgical site infection (SSI) surveillance is a key factor in the elaboration of strategies to reduce SSI occurrence and in providing surgeons with appropriate data feedback (risk indicators, clinical prediction rule). To improve the predictive performance of an individual-based SSI risk model by considering a multilevel hierarchical structure. Data were collected anonymously by the French SSI active surveillance system in 2011. An SSI diagnosis was made by the surgical teams and infection control practitioners following standardized criteria. A random 20% sample comprising 151 hospitals, 502 wards and 62280 patients was used. Three-level (patient, ward, hospital) hierarchical logistic regression models were initially performed. Parameters were estimated using the simulation-based Markov Chain Monte Carlo procedure. A total of 623 SSI were diagnosed (1%). The hospital level was discarded from the analysis as it did not contribute to variability of SSI occurrence (p  = 0.32). Established individual risk factors (patient history, surgical procedure and hospitalization characteristics) were identified. A significant heterogeneity in SSI occurrence between wards was found (median odds ratio [MOR] 3.59, 95% credibility interval [CI] 3.03 to 4.33) after adjusting for patient-level variables. The effects of the follow-up duration varied between wards (p<10-9), with an increased heterogeneity when follow-up was <15 days (MOR 6.92, 95% CI 5.31 to 9.07]). The final two-level model significantly improved the discriminative accuracy compared to the single level reference model (p<10-9), with an area under the ROC curve of 0.84. This study sheds new light on the respective contribution of patient-, ward- and hospital-levels to SSI occurrence and demonstrates the significant impact of the ward level over and above risk factors present at patient level (i.e., independently from patient case-mix).

  4. 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

  5. Characterization of Transverse Isotropy in Compressed Tissue Mimicking Phantoms

    PubMed Central

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

    2015-01-01

    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 which 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 0–360°, where the stress is applied along 0–180° 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

  6. Efficacy of rifampicin combination therapy for the treatment of enterococcal infections assessed in vivo using a Galleria mellonella infection model.

    PubMed

    Skinner, Kirsty; Sandoe, Jonathan A T; Rajendran, Ranjith; Ramage, Gordon; Lang, Sue

    2017-04-01

    Enterococci are a leading cause of healthcare-associated infection worldwide and display increasing levels of resistance to many of the commonly used antimicrobials, making treatment of their infections challenging. Combinations of antibiotics are occasionally employed to treat serious infections, allowing for the possibility of synergistic killing. The aim of this study was to evaluate the effects of different antibacterial combinations against enterococcal isolates using an in vitro approach and an in vivo Galleria mellonella infection model. Five Enterococcus faecalis and three Enterococcus faecium strains were screened by paired combinations of rifampicin, tigecycline, linezolid or vancomycin using the chequerboard dilution method. Antibacterial combinations that displayed synergy were selected for in vivo testing using a G. mellonella larvae infection model. Rifampicin was an effective antibacterial enhancer when used in combination with tigecycline or vancomycin, with minimum inhibitory concentrations (MICs) of each individual antibiotic being reduced by between two and four doubling dilutions, generating fractional inhibitory concentration index (FICI) values between 0.31 and 0.5. Synergy observed with the chequerboard screening assays was subsequently observed in vivo using the G. mellonella model, with combination treatment demonstrating superior protection of larvae post-infection in comparison with antibiotic monotherapy. In particular, rifampicin in combination with tigecycline or vancomycin significantly enhanced larvae survival. Addition of rifampicin to anti-enterococcal treatment regimens warrants further investigation and may prove useful in the treatment of enterococcal infections whilst prolonging the clinically useful life of currently active antibiotics.

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

    PubMed Central

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

    2015-01-01

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

  8. Intramedullary cervical neurenteric cyst mimicking an abscess.

    PubMed

    Muzumdar, D; Bhatt, Y; Sheth, J

    2008-01-01

    We describe a cervical intramedullary neurenteric cyst in a 12-year-old male patient who presented with gradual onset and progressively worsening neck pain, spastic quadriparesis and impaired sensation in the C(2) dermatome. MR imaging revealed a well-defined peripherally enhancing cystic intramedullary lesion with a posteroinferior enhancing nodule at the C(2)-C(3) level mimicking an abscess. There was no evidence of spinal dysraphism. The lesion was completely resected through a posterior approach and the patient showed radical improvement in his symptomatology. At follow-up after 3 years, he was asymptomatic and the MR imaging showed no evidence of any residual or recurrent cyst. The case presented here is unique, since a spinal neurenteric cyst showing intense peripheral contrast enhancement mimicking an abscess is unusual. The radiological features, pathogenesis and surgical considerations in cervical intramedullary neurenteric cysts are discussed and the relevant literature is briefly reviewed.

  9. 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.

  10. Pulmonary diseases with imaging findings mimicking aspergilloma.

    PubMed

    Gazzoni, Fernando Ferreira; Severo, Luiz Carlos; Marchiori, Edson; Guimarães, Marcos Duarte; Garcia, Tiago Severo; Irion, Klaus L; Camargo, José Jesus; Felicetti, José Carlos; de Mattos Oliveira, Flavio; Hochhegger, Bruno

    2014-06-01

    Patients with preexisting lung cavities are at risk of developing intracavitary fungal colonization. Because Aspergillus spp. are the most commonly implicated fungi, these fungal masses are called aspergillomas. Their characteristic "ball-in-hole" appearance, however, may be found in a variety of other conditions that can produce radiologic findings mimicking aspergilloma. In this paper, we review the main diseases that may mimic the radiographic findings of aspergilloma, with brief descriptions of clinical, radiologic, and histopathologic findings.

  11. 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.

  12. A Pilocytic Astrocytoma Mimicking a Clinoidal Meningioma

    PubMed Central

    Hong, Christopher S.; Lehman, Norman L.; Sauvageau, Eric

    2014-01-01

    Pilocytic astrocytomas and meningiomas are benign, primary brain tumors that may involve the optic tract. Classically, the presence of a dural “tail” sign may differentiate a meningioma from other intracranial lesions. In this report, we describe a mass with the typical appearance of a clinoidal meningioma on magnetic resonance imaging (MRI) but postoperatively diagnosed as a pilocytic astrocytoma. This case illustrates the rare occurrence of a pilocytic astrocytoma mimicking a meningioma on MRI. PMID:24744944

  13. 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

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

    PubMed Central

    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

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

    PubMed Central

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

    2015-01-01

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

  16. Modeling Antiretroviral Drug Responses for HIV-1 infected Patients Using Differential Equation Models

    PubMed Central

    Xiao, Yanni; Miao, Hongyu; Tang, Sanyi; Wu, Hulin

    2014-01-01

    Summary We review mathematical modeling and related statistical issues of HIV dynamics primarily in response to antiretroviral drug therapy in this article. We start from a basic model of virus infection and then review a number of more advanced models with considering, e.g., pharmacokinetic factors, adherence and drug resistance. Specifically, we illustrate how mathematical models can be developed and parameterized to understand effects of long-term treatment and different treatment strategies on disease progression. In addition, we discuss a variety of parameter estimation methods for differential equation models that are applicable to either within- or between-host viral dynamics. PMID:23603208

  17. Modeling antiretroviral drug responses for HIV-1 infected patients using differential equation models.

    PubMed

    Xiao, Yanni; Miao, Hongyu; Tang, Sanyi; Wu, Hulin

    2013-06-30

    We review mathematical modeling and related statistical issues of HIV dynamics primarily in response to antiretroviral drug therapy in this article. We start from a basic model of virus infection and then review a number of more advanced models with consideration of pharmacokinetic factors, adherence and drug resistance. Specifically, we illustrate how mathematical models can be developed and parameterized to understand the effects of long-term treatment and different treatment strategies on disease progression. In addition, we discuss a variety of parameter estimation methods for differential equation models that are applicable to either within- or between-host viral dynamics.

  18. Tupaia Belangeri as an Experimental Animal Model for Viral Infection

    PubMed Central

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development. PMID:25048261

  19. Cryptococcus neoformans as a Model for Radioimmunotherapy of Infections

    PubMed Central

    Dadachova, Ekaterina; Casadevall, Arturo

    2011-01-01

    There is an obvious and urgent need for novel approaches to treat infectious diseases. The use of monoclonal antibodies in therapy of infectious diseases is now experiencing renewed interest. During the last 5 years radioimmunotherapy (RIT), a modality previously developed only for cancer treatment, has been successfully adapted for the treatment of experimental fungal, bacterial, and viral infections. As our model organism for studying the efficacy, mechanisms, potential toxicity, and radioresistance to RIT, as well as for comparison of RIT with the existing antimicrobial therapies we have chosen the encapsulated yeast Cryptococcus neoformans (CN). The success of RIT approach in laboratory studies provides encouragement for feasibility of therapeutically targeting microbes with labeled antibodies. In addition, the creation of “panantibodies” for RIT which would recognize antigens shared by the whole class of pathogens such as fungi, for example, would facilitate the introduction of RIT into the clinic. PMID:21747848

  20. Tupaia belangeri as an experimental animal model for viral infection.

    PubMed

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  1. Infection

    MedlinePlus

    ... or articles contaminated by them is an important component of infection control and isolation precautions. To help protect exposure to infectious materials, wash your hands: Wear gloves: In addition to ...

  2. Models of Respiratory Infections: Virus-Induced Asthma Exacerbations and Beyond

    PubMed Central

    Saturni, Sara; Contoli, Marco; Spanevello, Antonio

    2015-01-01

    Respiratory infections are one of the main health problems worldwide. They are a challenging field of study due to an intricate relationship between the pathogenicity of microbes and the host's defenses. To better understand mechanisms of respiratory infections, different models have been developed. A model is the reproduction of a disease in a system that mimics human pathophysiology. For this reason, the best models should closely resemble real-life conditions. Thus, the human model is the best. However, human models of respiratory infections have some disadvantages that limit their role. Therefore, other models, including animal, in vitro, and mathematical ones, have been developed. We will discuss advantages and limitations of available models and focus on models of viral infections as triggers of asthma exacerbations, viral infections being one of the most frequent causes of exacerbating disease. Future studies should focus on the interrelation of various models. PMID:26333698

  3. Humanized-BLT mouse model of Kaposi's sarcoma-associated herpesvirus infection.

    PubMed

    Wang, Lin-Xu; Kang, Guobin; Kumar, Pankaj; Lu, Wuxun; Li, Yue; Zhou, You; Li, Qingsheng; Wood, Charles

    2014-02-25

    Lack of an effective small-animal model to study the Kaposi's sarcoma-associated herpesvirus (KSHV) infection in vivo has hampered studies on the pathogenesis and transmission of KSHV. The objective of our study was to determine whether the humanized BLT (bone marrow, liver, and thymus) mouse (hu-BLT) model generated from NOD/SCID/IL2rγ mice can be a useful model for studying KSHV infection. We have tested KSHV infection of hu-BLT mice via various routes of infection, including oral and intravaginal routes, to mimic natural routes of transmission, with recombinant KSHV over a 1- or 3-mo period. Infection was determined by measuring viral DNA, latent and lytic viral transcripts and antigens in various tissues by PCR, in situ hybridization, and immunohistochemical staining. KSHV DNA, as well as both latent and lytic viral transcripts and proteins, were detected in various tissues, via various routes of infection. Using double-labeled immune-fluorescence confocal microscopy, we found that KSHV can establish infection in human B cells and macrophages. Our results demonstrate that KSHV can establish a robust infection in the hu-BLT mice, via different routes of infection, including the oral mucosa which is the most common natural route of infection. This hu-BLT mouse not only will be a useful model for studying the pathogenesis of KSHV in vivo but can potentially be used to study the routes and spread of viral infection in the infected host.

  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 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,...

  6. Experimental Porcine Toxoplasma gondii Infection as a Representative Model for Human Toxoplasmosis.

    PubMed

    Nau, Julia; Eller, Silvia Kathrin; Wenning, Johannes; Spekker-Bosker, Katrin Henrike; Schroten, Horst; Schwerk, Christian; Hotop, Andrea; Groß, Uwe; Däubener, Walter

    2017-01-01

    Porcine infections are currently not the state-of-the-art model to study human diseases. Nevertheless, the course of human and porcine toxoplasmosis is much more comparable than that of human and murine toxoplasmosis. For example, severity of infection, transplacental transmission, and interferon-gamma-induced antiparasitic effector mechanisms are similar in pigs and humans. In addition, the severe immunosuppression during acute infection described in mice does not occur in the experimentally infected ones. Thus, we hypothesise that porcine Toxoplasma gondii infection data are more representative for human toxoplasmosis. We therefore suggest that the animal model chosen must be critically evaluated for its assignability to human diseases.

  7. Quantifying Vibrio cholerae enterotoxicity in a zebrafish infection model.

    PubMed

    Mitchell, Kristie C; Breen, Paul; Britton, Sarah; Neely, Melody N; Withey, Jeffrey H

    2017-06-16

    Vibrio cholerae is the etiological agent of cholera, an acute intestinal infection in humans characterized by voluminous watery diarrhea. Cholera is spread through ingestion of contaminated food or water, primarily in developing countries that lack the proper infrastructure for proper water and sewage treatment. Vibrio cholerae is an aquatic bacterium that inhabits coastal and estuarine areas, and is known to have several environmental reservoirs, including fish. Our laboratory has recently described the use of the zebrafish as a new animal model for the study of V. cholerae intestinal colonization, pathogenesis, and transmission.As early as six hours after exposure to V. cholerae, zebrafish develop diarrhea. Prior work in our laboratory has shown that this is not due to the action of cholera toxin. We hypothesize that accessory toxins produced by V. cholerae are the cause of diarrhea in infected zebrafish. In order to assess the effects of accessory toxins in the zebrafish, it was necessary to develop a method of quantifying diarrheal volume as a measure of pathogenesis. Here, we have adapted cell density, protein, and mucin assays, along with enumeration of V. cholerae in the zebrafish intestinal tract and in the infection water, to achieve this goal. Combined, these assays should help us determine which toxins have the greatest diarrheagenic effect in fish, and consequently, which toxins may play a role in environmental transmission.Importance Identification of the accessory toxins that cause diarrhea in zebrafish can help us understand more about the role of fish in the wild as aquatic reservoirs for V. cholerae It is plausible that accessory toxins can act to prolong colonization and subsequent shedding of V. cholerae back into the environment, thus perpetuating and facilitating transmission during an outbreak. It is also possible that accessory toxins help to maintain low levels of intestinal colonization in fish, giving V. cholerae an advantage when

  8. Animal models, prophylaxis, and therapeutics for arenavirus infections.

    PubMed

    Vela, Eric

    2012-09-01

    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.

  9. 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

  10. Dermatophytosis caused by Trichophyton rubrum mimicking syphilid: a case report and review of literature.

    PubMed

    Tan, Yongfang; Lin, Liangbao; Feng, Peiying; Lai, Wei

    2014-05-01

    A 56-year-old man who was under chemotherapy presented with a 2-week history of erythema on the left palm, soles, glans penis and the foreskin with no itching and pain. Initially syphilid was suspected. However, both toluidine red unheated serum test (TRUST) and treponema pallidum particle agglutination assay (TPPA) were negative. Microscopy showed hyphae in all sites and skin culture revealed Trichophyton rubrum infection, consistent with the diagnosis of tinea infection. He was cured with oral terbinafine for 2 weeks. We report here a case of tinea incognito caused by T. rubrum mimicking syphilid and review the literature. © 2013 Blackwell Verlag GmbH.

  11. 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.

  12. 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

  13. Modeling competition for infection sites on roots by nonpathogenic strains of Fusarium oxysporum.

    PubMed

    Mandeel, Qaher A

    2007-01-01

    By use of plane and solid geometry and probability models, efficiencies of infection and competition for nutrients and infection sites by a nonpathogenic strain of Fusarium oxysporum (C14) with F. oxysporum f. sp. cucumerinum on the rhizoplane of cucumber were calculated. The model is derived from previously published data. Efficiencies for successful infection were 0.04 chlamydospores per infection site for both pathogen and nonpathogen. Observed successful infections by the pathogen in competition with the nonpathogen were close in values to the competition ratio (CR) calculated as the number of chlamydospores on the infection court of the pathogen divided by the total number of both pathogen and nonpathogen at relatively low densities. When total chlamydospores were, on average, closer than 175 microm apart, however, competition for nutrients/mutual inhibition occurred. At such densities there was an overestimation of the effect of competition for infection sites. These relationships were modeled at inoculum densities of pathogen and/or nonpathogen of 5000 chlamydospores per g soil and above, however, in the field, maximum densities of 1000 colony forming units/g (cfu) were observed. Most likely models of competition for infection sites at this density of the pathogen revealed that infection efficiency was only approximately halved, even when 0.98 of the possible 30 infection sites were occupied by the nonpathogen. It is conclude that competition for nutrients and/or infection sites is an insignificant factor in biocontrol of Fusarium wilt diseases by nonpathogenic fusaria.

  14. 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

  15. Brucellosis in spondyloarthritis mimicking an exacerbation.

    PubMed

    Garip, Y; Eser, F; Erten, S; Yilmaz, O; Yildirim, P

    2014-01-01

    Spondyloarthritis are a group of chronic inflammatory diseases that affect the axial skeleton, entheses and peripheral joints and may have extraarticular manifestations such as uveitis, psoriasis and inflammatory bowel disease. Brucellosis is a systemic infectious disease, endemic in Middle East, Latin America, and Mediterranean countries, which may present manifestations that resemble other diseases posing serious problems of differential diagnosis. Some hallmarks of Brucellosis may mimic a spondyloarthritis flare. In this paper, authors present a clinical case of brucellosis occurring in a patient with spondyloarthritis. Clinical symptoms initially mimicked exacerbation of spondyloarthritis.

  16. Thymic Langerhans cell histiocytosis mimicking lymphoma.

    PubMed

    Yağci, Begül; Varan, Ali; Uner, Aysegül; Akyüz, Canan; Büyükpamukçu, Münevver

    2008-12-01

    Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal expansion of antigen presenting Langerhans cells. Different clinical features can be seen according to the involved organs and systems. Multisystem disease with organ dysfunction is more common in infants, whereas single system disease is usually observed in older children. The disease can affect any system or organ throughout the body. Thymus is a rarely involvement site reported in LCH and usually is accompanied by skin, bone or lung disease. Here we report a 12-year-old male with thymic involvement by LCH clinically mimicking lymphoma.

  17. 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.

  18. 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.

  19. Intradural Extramedullary Tuberculoma Mimicking En Plaque Meningioma

    PubMed Central

    Shim, Dae Moo; Kim, Tae Kyun; Chae, Soo Uk

    2010-01-01

    A 24-year-old man with tuberculosis meningitis developed acute paraplegia and sensory disturbances 5 weeks after receiving conventional antituberculous therapy. Magnetic resonance imaging revealed an intradural extramedullary long segmental mass mimicking en plaque meningioma at the T2-T6 vertebrae levels. Prompt surgical decompression was performed. A histology examination of the mass revealed a tuberculoma. After surgery, the patient showed improved motor power and a normal bladder function. Intradural extramedullary tuberculoma of the spinal cord is rare complication of tuberculosis meningitis, which can occur as a response to conventional antituberculous therapy. PMID:21119945

  20. Pulmonary tumour microembolism clinically mimicking alveolitis

    PubMed Central

    Lo, A W I; Tse, G M K; Chu, W C W; Chan, A B W

    2003-01-01

    A 56 year old man with previously unsuspected recurrence of squamous cell carcinoma of the oesophagus presented with dyspnoea. Bronchoscopy and computed tomography suggested bronchopneumonic changes with an infectious cause. He suffered a rapidly deteriorating course and died despite active treatment, including antibiotics and mechanical ventilation. Necropsy revealed a florid pulmonary tumour microembolism mimicking alveolitis. No bronchopneumonia was seen. The emboli arose from loosely attached tumour vegetations in the tricuspid valve. In a patient with known malignancy, tumour microembolism should be considered as an uncommon cause of rapid respiratory failure, refractory to antibiotic treatment. PMID:14600135

  1. Enteroaggregative Escherichia coli (EAEC) impairs growth while malnutrition worsens EAEC infection: a novel murine model of the infection malnutrition cycle.

    PubMed

    Roche, James K; Cabel, Ace; Sevilleja, Jesus; Nataro, James; Guerrant, Richard L

    2010-08-15

    Enteroaggregative Escherichia coli is emerging as an increasingly recognized cause of persistent, mildly inflammatory diarrhea in the United States, especially among patients with AIDS, as well as among children, for whom it is accompanied by growth shortfalls. We describe a novel model of disease induced in neonatal and weaned C57BL/6 mice by pathogenic strains of enteroaggregative E. coli 042 and JM221. Enteroaggregative E. coli caused growth impairment (up to 47%), persistent stool shedding (for >3 weeks), and a substantial tissue burden of organisms (150,000 organisms per milligram of tissue), as well as histopathological changes in the colonic epithelium (days 4 and 6 of infection) using the model. Undernutrition in neonatal mice, as well as in weaned mice, intensified infection by 1-4 logs, as assessed by quantitative polymerase chain reaction for fecal shedding of organisms. Growth impairment was dependent on both microorganism burden and challenge dose. Both neonatal and weaned mice provide models for a vicious cycle of enteroaggregative E. coli infection that causes growth shortfalls and undernutrition, thus worsening infection. Hence, these neonatal and weaned mice provide the opportunity to dissect mechanisms of this cycle in childhood malnutrition, as well as to define the role played by innate and acquired host defenses in this important infection.

  2. Modelling HIV-RNA viral load in vertically infected children.

    PubMed

    Gray, Linsay; Cortina-Borja, Mario; Newell, Marie-Louise

    2004-03-15

    Human immunodeficiency virus (HIV) ribo-nucleic acid (RNA) viral load is a measure of actively replicating virus and is used as a marker of disease progression. For a thorough understanding of the dynamics of the evolution of the virus in the early life of HIV-1 vertically infected children, it is important to elucidate the pattern of HIV-RNA viral load over age. An aspect of assay systems used in the quantification of RNA viral load is that they measure values above particular cut-off values for detection, below which the assays used are not sufficiently sensitive. In this way, measurements are potentially left-censored. Recent adult studies suggest that to adequately model RNA pattern over age, it is necessary to account for within-subject correlation, due to repeated measures, and censoring. The aim of this study, therefore, was to establish whether it is necessary to use complex methods to allow for repeated measures within individuals and censoring of the HIV-RNA viral load in children enrolled in a cohort study. The approach involved the identification of an appropriate model for the basic pattern of RNA viral load by age and subsequent assessment of various estimation procedures accounting for repeated measures and censoring in different ways. Methods developed by Hughes involving the expectation-maximization (EM) algorithm and the Gibbs sampler were taken as the benchmark for comparison of simpler alternatives. Other approaches considered involve linear mixed-effects and ordinary least squares in which censoring is dealt with informally by taking the cut-off value as absolute or taking the mid-point between cut-off and zero. Fractional polynomials provided a substantially superior approach for modelling the dynamics of viral load over age compared to conventional polynomials or change-point models. Allowing for repeated measures was necessary to improve the power of the likelihood ratio tests required to establish the final model, but methods beyond taking

  3. Establishment of a Neonatal Rhesus Macaque Model to Study Mycobacterium tuberculosis Infection

    PubMed Central

    Cepeda, Magdalena; Salas, Mary; Folwarczny, Jessica; Leandro, Ana C.; Hodara, Vida L.; de la Garza, Melissa A.; Dick, Edward J.; Owston, Michael; Armitige, Lisa Y.; Gauduin, Marie-Claire

    2014-01-01

    Summary Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS. PMID:24388650

  4. 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.

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

    PubMed

    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.

  6. Novel In Vitro/Ex Vivo Animal Modeling for Filovirus Aerosol Infection

    DTIC Science & Technology

    2014-09-01

    Infection PRINCIPAL INVESTIGATOR: Ayesha Mahmood, Ph.D. CONTRACTING ORGANIZATION: Sanofi Pasteur VaxDesign Corporation...12-2-0071 Novel in vitro/ex vivo animal modeling for Filovirus aerosol infection 5b. GRANT NUMBER W81XWH-12-2-0071 5c. PROGRAM ELEMENT NUMBER 6...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The “Novel in vitro / ex vivo animal modeling for filovirus aerosol infection ” program is

  7. 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.

  8. The Baboon (Papio spp.) as a Model of Human Ebola Virus Infection

    PubMed Central

    Perry, Donna L.; Bollinger, Laura; L.White, Gary

    2012-01-01

    Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited. PMID:23202470

  9. 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.

  10. Clinical and Histologic Mimickers of Celiac Disease.

    PubMed

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  11. Doxycycline-induced ulceration mimicking esophageal cancer

    PubMed Central

    Tahan, Veysel; Sayrak, Hakan; Bayar, Nevzat; Erer, Burak; Tahan, Gulgun; Dane, Faysal

    2008-01-01

    Introduction Doxycycline-induced esophageal ulcer patients are mostly young persons with no history of esophageal dysfunction. Heartburn, midsternal pain and dysphagia are the most common symptoms. It has generally a benign course. The present case is the first report of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments alongside, in the literature. Case presentation This report describes a 16-year-old Caucasian girl who, while taking doxycycline capsules100 mg twice a day for acne vulgaris for 3 months, developed these symptoms. An upper endoscopy revealed multiple circumferential deep ulcerations surrounding fragile, irregular, hyperemic and hypertrophic mucosa at the level of the mid-esophagus and concomitantly in the lower esophageal sphincter. The lesions were biopsied to exclude esophageal carcinoma because of the suspicious appearance in the endoscopic examination. The histopathological examination, haematoxylin and eosin stained sections showed ulceration with a mixed inflammatory infiltrate. Doxycycline was discontinued and she was given sucralfate 1 g qid and omeprazole 20 mg bid orally. All symptoms of the patient were resolved on the third day of the treatment. After 4 weeks of the therapy, an upper endoscopic control examination demonstrated normal findings. Conclusion The present case has been an uncommon presentation of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments, concomitantly. Even the lesions were biopsied to exclude esophageal carcinoma. A modification on the behavior of taking drugs can prevent these unpleasant complications. PMID:18778470

  12. 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.

  13. Nonlinearity parameter for tissue-mimicking materials.

    PubMed

    Dong, F; Madsen, E L; MacDonald, M C; Zagzebski, J A

    1999-06-01

    A finite amplitude insert-substitution method has been used to determine the ultrasonic nonlinearity parameter B/A of nine versions of water-based, macroscopically uniform ultrasonically tissue-mimicking (TM) nonfat and fat materials. In this method, the amplitude of the second harmonic following transmission through degassed distilled water with known B/A (B/A = 5.2) and the amplitude of the second harmonic following transmission through the unknown sample are measured. The ratio of these amplitudes allows calculation of the B/A of the sample. Measured B/A values of the nonfat materials range from 5.6 to 6.6. These values compare favorably with published values for nonfat soft tissues. In contrast, the measured B/A values for two tissue-mimicking fat materials are 9.8 and 11.1; these two values represent the low and high end of B/A for most fresh fatty tissues. For comparison, B/A was measured for two commonly available uniform materials, corn oil and ethylene glycol, and the results are in good agreement with published values.

  14. 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

  15. 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…

  16. 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…

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

    PubMed

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

    2016-01-05

    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. 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. 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. 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.

  18. 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

  19. Acute and Late Bartonella henselae Murine Model Infection.

    PubMed

    da Silva, Marilene Neves; Vieira-Damiani, Gislaine; Ericson, Marna Elise; Gupta, Kalpna; de Almeida, Amanda Roberta; Drummond, Marina Rovani; Soares, Tania Cristina Benetti; Lania, Bruno Grosselli; Gilioli, Rovilson; Velho, Paulo Eduardo Neves Ferreira

    2017-03-01

    Bartonella spp. are fastidious gram-negative neglected bacilli with worldwide distribution. They are able to cause intraerythrocytic and potentially fatal infection. Cats and dogs are reservoirs of some species of these agents. Blood-sucking arthropods are potential vectors. Our aim was to evaluate the blood, skin, liver, and spleen in BALB/c mice by using molecular tests and confocal microscopy to demonstrate Bartonella henselae infection in the bloodstream and organs after 4 and 21 days of intraperitoneally injected bacterial suspension. We demonstrate that the occurrence of infection in organs precedes the detectable infection in blood. Therefore, late manifestation in blood may be another challenge in early detection and diagnosis of B. henselae infection.

  20. Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

    PubMed Central

    2014-01-01

    Background The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen. Methods We established a C. elegans – S. aureus liquid-based assay to screen for potential anti-infectives against S. aureus. The assay was utilized to screen 37 natural extracts and 29 synthetic compounds for the ability to extend the lifespan of infected nematodes. Disc diffusion and MIC microdilution tests were used to evaluate the anti-microbial properties of these natural extracts and synthetic compounds whilst in vivo bacterial CFU within the C. elegans gut were also enumerated. Results We screened a total of 37 natural extracts and 29 synthetic compounds for anti-infective properties. The screen successfully revealed 14 natural extracts from six plants (Nypa fruticans, Swietenia macrophylla, Curcuma longa, Eurycoma longifolia, Orthosiphon stamineus and Silybum eburneum) and one marine sample (Faunus ater) that improved the survival of S. aureus-infected worms by at least 2.8-fold as well as 14 synthetic compounds that prolonged the survival of S. aureus-infected nematodes by 4-fold or greater. An anti-microbial screen of all positive hits demonstrated that 8/28 hits had no effect on S. aureus growth. Of these 8 candidates, 5 of them also protected the worms from MRSA infection. We also noted that worms exposed to N. fruticans root and O. stamineus leaf extracts showed reduced intestinal colonization by live S. aureus. This suggests that these extracts could possibly activate host immunity to eliminate the bacteria or interfere with factor/s that prevents pathogen accumulation. Conclusion We have successfully

  1. Modeling and prediction of HIV in China: transmission rates structured by infection ages.

    PubMed

    Zhou, Yican; Shao, Yiming; Ruan, Yuhua; Xu, Jianqing; Ma, Zhien; Mei, Changlin; Wu, Jianhong

    2008-04-01

    HIV transmission process involves a long incubation and infection period, and the transmission rate varies greatly with infection stage. Consequently, modeling analysis based on the assumption of a constant transmission rate during the entire infection period yields an inaccurate description of HIV transmission dynamics and long-term projections. Here we develop a general framework of mathematical modeling that takes into account this heterogeneity of transmission rate and permits rigorous estimation of important parameters using a regression analysis of the twenty-year reported HIV infection data in China. Despite the large variation in this statistical data attributable to the knowledge of HIV, surveillance efforts, and uncertain events, and although the reported data counts individuals who might have been infected many years ago, our analysis shows that the model structured on infection age can assist us in extracting from this data set very useful information about transmission trends and about effectiveness of various control measures.

  2. 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

  3. Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants.

    PubMed

    Jaggessar, Alka; Shahali, Hesam; Mathew, Asha; Yarlagadda, Prasad K D V

    2017-10-02

    Orthopaedic and dental implants have become a staple of the medical industry and with an ageing population and growing culture for active lifestyles, this trend is forecast to continue. In accordance with the increased demand for implants, failure rates, particularly those caused by bacterial infection, need to be reduced. The past two decades have led to developments in antibiotics and antibacterial coatings to reduce revision surgery and death rates caused by infection. The limited effectiveness of these approaches has spurred research into nano-textured surfaces, designed to mimic the bactericidal properties of some animal, plant and insect species, and their topographical features. This review discusses the surface structures of cicada, dragonfly and butterfly wings, shark skin, gecko feet, taro and lotus leaves, emphasising the relationship between nano-structures and high surface contact angles on self-cleaning and bactericidal properties. Comparison of these surfaces shows large variations in structure dimension and configuration, indicating that there is no one particular surface structure that exhibits bactericidal behaviour against all types of microorganisms. Recent bio-mimicking fabrication methods are explored, finding hydrothermal synthesis to be the most commonly used technique, due to its environmentally friendly nature and relative simplicity compared to other methods. In addition, current proposed bactericidal mechanisms between bacteria cells and nano-textured surfaces are presented and discussed. These models could be improved by including additional parameters such as biological cell membrane properties, adhesion forces, bacteria dynamics and nano-structure mechanical properties. This paper lastly reviews the mechanical stability and cytotoxicity of micro and nano-structures and materials. While the future of nano-biomaterials is promising, long-term effects of micro and nano-structures in the body must be established before nano-textures can

  4. 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.

  5. 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.

  6. IL-22 exacerbates weight loss in a murine model of chronic pulmonary Pseudomonas aeruginosa infection.

    PubMed

    Bayes, Hannah K; Ritchie, Neil D; Ward, Christopher; Corris, Paul A; Brodlie, Malcolm; Evans, Thomas J

    2016-11-01

    Interleukin (IL)-22 is a critical mediator of mucosal immunity and tissue regeneration, protecting against a number of respiratory pathogens. Whether IL-22 confers protection against chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is unknown. Explanted CF lungs were examined for IL-22 production and immune-localization. A murine model of persistent pulmonary PA infection was used to examine production of IL-22 following infective challenge. The role of IL-22 was examined using IL-22 knockout (KO) animals. IL-22 is produced within the adult CF lung and localizes to the airway epithelium. IL-22 is produced by murine pulmonary lymph node cells following lung infection. The absence of IL-22 resulted in no significant difference in acute mortality, bacterial burden, chronic infection rates, histological changes or neutrophilic inflammation in the chronic PA infection model. However, IL-22 KO animals lost less weight following infection. IL-22 is produced in the CF lung and in response to PA infection yet is dispensable in protection against chronic pulmonary P. aeruginosa infection in a murine model. However, we identified a novel role for the cytokine in promoting infection-related weight-loss, a significant prognostic factor in the CF population. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Stochastic modeling for dynamics of HIV-1 infection using cellular automata: A review.

    PubMed

    Precharattana, Monamorn

    2016-02-01

    Recently, the description of immune response by discrete models has emerged to play an important role to study the problems in the area of human immunodeficiency virus type 1 (HIV-1) infection, leading to AIDS. As infection of target immune cells by HIV-1 mainly takes place in the lymphoid tissue, cellular automata (CA) models thus represent a significant step in understanding when the infected population is dispersed. Motivated by these, the studies of the dynamics of HIV-1 infection using CA in memory have been presented to recognize how CA have been developed for HIV-1 dynamics, which issues have been studied already and which issues still are objectives in future studies.

  8. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    NASA Astrophysics Data System (ADS)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  9. 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.

  10. Modelling the course of an HIV infection: insights from ecology and evolution.

    PubMed

    Alizon, Samuel; Magnus, Carsten

    2012-10-04

    The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi's sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection.

  11. Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

    PubMed Central

    Alizon, Samuel; Magnus, Carsten

    2012-01-01

    The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection. PMID:23202449

  12. 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

  13. 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.

  14. Modeling Powassan virus infection in Peromyscus leucopus, a natural host

    PubMed Central

    Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E.

    2017-01-01

    The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study. PMID:28141800

  15. Modeling Powassan virus infection in Peromyscus leucopus, a natural host.

    PubMed

    Mlera, Luwanika; Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E

    2017-01-01

    The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study.

  16. Alzheimer's disease and peripheral infections: the possible contribution from periodontal infections, model and hypothesis.

    PubMed

    Kamer, Angela R; Dasanayake, Ananda P; Craig, Ronald G; Glodzik-Sobanska, Lidia; Bry, Miroslow; de Leon, Mony J

    2008-05-01

    Alzheimer's disease (AD) affects approximately 4.5 million people in the U.S. and this number will increase as the population ages and the life-span increases. Therefore, of paramount importance is identifying mechanisms and factors that affect the risk of developing AD. The etiology and pathogenic mechanisms for AD have not been defined, although inflammation within the brain is thought to play a role. Consistent with this hypothesis, studies suggest that peripheral infections contribute to the inflammatory state of the central nervous system. Periodontitis is a prevalent, persistent peripheral infection associated with gram negative, anaerobic bacteria that are capable of exhibiting localized and systemic infections in the host. This review offers a hypothetical link between periodontitis and AD and will present possible mechanistic links between periodontitis related inflammation and AD. It will review the pathogenesis of periodontitis and the mechanisms by which periodontal infections may affect the onset and progression of AD. Since periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

  17. CMV Infection Attenuates the Disease Course in a Murine Model of Multiple Sclerosis

    PubMed Central

    Pirko, Istvan; Cardin, Rhonda; Chen, Yi; Lohrey, Anne K.; Lindquist, Diana M.; Dunn, R. Scott; Zivadinov, Robert; Johnson, Aaron J.

    2012-01-01

    Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies. PMID:22393447

  18. High-altitude cerebral oedema mimicking stroke

    PubMed Central

    Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

    2014-01-01

    High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO. PMID:24671373

  19. 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

  20. Orthokeratinised odontogenic cyst mimicking periapical cyst.

    PubMed

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

    2013-10-07

    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.

  1. Mature posterior fossa teratoma mimicking dermoid cyst.

    PubMed

    Bohara, Manoj; Yonezawa, Hajime; Karki, Prasanna; Bakhtiar, Yuriz; Hirano, Hirofumi; Kitazono, Ikumi; Matsuyama, Nozomu; Arita, Kazunori

    2013-10-01

    We describe a very rare case of mature posterior fossa teratoma in an adult who presented with clinico-radiological findings consistent with a dermoid cyst. A computed tomography scan showed a hypodense mass in the cistern magna with calcification and a sinus tract in the occipital bone. Magnetic resonance imaging revealed a hypo- to hyperintense mass without contrast enhancement. The intraoperative picture showed a dermal sinus and a cyst containing lipid, keratin and hair. Histopathological examination showed a tumor with components of all the three germ layers; thereby, a diagnosis of mature teratoma was made. The histopathological differentiation between teratoma and dermoid cyst is very valuable for ruling out the presence of immature/malignant or germinomatous components that would require further adjuvant therapies. Thus, we here present a rare case of posterior fossa teratoma mimicking dermoid cyst and emphasize the importance of histopathological differentiation between these entities.

  2. Infant botulism mimicking an acute abdomen.

    PubMed

    Pisanti, R; Vitiello, R; Formicola, S; Pisanti, A

    2009-12-01

    Botulism is the acute, flaccid paralysis caused by a neurotoxin produced by Clostridium botulinum. In the infant, clinical symptoms are usually unspecific such as poor feeding, weak suck, feeble cry, drooling, followed by a symmetric, descending, flaccid paralysis beginning with the cranial nerve musculature. The initial symptoms of the disease are often similar to several diseases and therefore differential diagnosis is very difficult and rarely suspected by the physician. Since 2004 only 22 cases of infant botulism have been reported in Italy. Since most paediatricians are unfamiliar with the clinical manifestations of infant botulism, the diagnosis can be easily missed. Hence the disease may well be underestimated and underreported. We report a clinical case of botulism presenting initially with abdominal distention, thereby mimicking acute abdomen.

  3. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Roberts, Jason D; Veinot, John P; Rutberg, Julie; Gollob, Michael H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Pulmonary artery sarcoma mimicking pulmonary thromboembolism.

    PubMed

    Celik, Gökhan; Ciledağ, Aydin; Yüksel, Cabir; Yenigün, Bülent Mustafa; Kutlay, Hakan; Yazicıoğlu, Levent; Perçinel, Sibel; Kaya, Akin

    2011-01-01

    A 30 years old male patient was referred to our hospital with a diagnosis of pulmonary thromboembolism due to thorax-computerized tomography (CT) angiography, revealing a thrombus totally occluding left main pulmonary artery. The lesion was evaluated as tumoural mass. Positron emission tomography (PET)-CT revealed pathologic uptake at pulmonary artery mass. Due to localization of tumour, left pneumonectomy was performed. The pathological diagnosis revealed to be pulmonary artery sarcoma. The patient was presented because pulmonary artery sarcomas are very rare tumors and can mimick pulmonary thromboembolism. The true prevalence is underestimated as many pulmonary artery sarcomas are misdiagnosed as pulmonary thromboembolism. PET-CT may help to make a differential diagnosis.

  5. Mimicking semi-convection by convective overshooting

    NASA Astrophysics Data System (ADS)

    Caloi, V.; Mazzitelli, I.

    1990-12-01

    This paper investigates the behavior of so called 'semiconvection' (described by Schwarzschild, 1970; Castellani et al., 1971), of stars burning He in a convective core but exibiting an apparent spontaneous capability to partially mix into the core the matter from outside the formal boundaries of the convective region. A simple numerical algorithm based on a small and ad hoc amount of convective overshooting is presented which, if properly tuned, can mimick the effect of semiconvection in the computation of those stellar evolutionary phases in which a convective helium burning core is present. Using this algorithm, the time-consuming numerical procedures involved in the evaluation of the correct chemical profiles at the boundaries of the formally convective He core can be avoided.

  6. 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

  7. Polypoid uterine lesions mimicking endometrial stromal sarcoma.

    PubMed Central

    McCluggage, W G; Alderdice, J M; Walsh, M Y

    1999-01-01

    Two polypoid submucosal uterine lesions were examined histologically and immunohistochemically with monoclonal antibodies to desmin and alpha smooth muscle actin. One case comprised a leiomyoma and the other a polypoid form of adenomyosis. Both polyps had prolapsed through the external cervical os. The lesions had an ulcerated surface with focal areas of marked increased cellularity and pronounced vascularity throughout, such that they mimicked a low grade endometrial stromal sarcoma infiltrating the myometrium. The cellular areas showed diffuse positivity for desmin and alpha smooth muscle actin, confirming them to be of smooth muscle origin. The changes of marked hypercellularity and pronounced vascularity within polypoid submucosal uterine lesions have not been emphasised in published reports up to now. Pathologists should be aware of these morphological features in order to avoid misdiagnosis of such cases as endometrial stromal sarcomas. The changes described here are likely to be secondary to trauma associated with a polypoid lesion prolapsing through the external cervical os. Images PMID:10605413

  8. Phthriasis Palpebrarum Mimicking Lid Eczema and Blepharitis

    PubMed Central

    Turgut, Burak; Kurt, Julide; Çatak, Onur; Demir, Tamer

    2009-01-01

    Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis. We report a case of PP mimicking lid eczema and blepharitis. A 68-year-old woman had moderate itching in both eyes. Her initial diagnosis was considered to be lid eczema or blepharitis because of findings similar to exfoliative lesions and color changes in eyelids and to excretions over eyelashes. Careful observation revealed many lice and translucent nits, protuberances and hyperpigmentary changes, and the buried lice in both eyelids. No hyperemia or secretion was observed on the lids and in the conjunctiva in both eyes. The patient was treated with pilocarpine hydrochloride 4% drops. At the end of the first week, no louse or nit was present. Although it was known that PP is a rare cause of blepharoconjunctivitis, it might observe as an isolated infestation of the eyelids and this condition can easily be misdiagnosed as lid eczema and blepharitis. PMID:20339456

  9. A diffusive virus infection dynamic model with nonlinear functional response, absorption effect and chemotaxis

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Ma, Wanbiao; Lai, Xiulan

    2017-01-01

    From a biological perspective, a diffusive virus infection dynamic model with nonlinear functional response, absorption effect and chemotaxis is proposed. In the model, the diffusion of virus consists of two parts, the random diffusion and the chemotactic movement. The chemotaxis flux of virus depends not only on their own density, but also on the density of infected cells, and the density gradient of infected cells. The well posedness of the proposed model is deeply investigated. For the proposed model, the linear stabilities of the infection-free steady state E0 and the infection steady state E* are extensively performed. We show that the threshold dynamics can be expressed by the basic reproduction number R0 of the model without chemotaxis. That is, the infection-free steady state E0 is globally asymptotically stable if R0 < 1, and the virus is uniformly persistent if R0 > 1. In addition, we use the cross iteration method and the Schauder's fixed point theorem to prove the existence of travelling wave solutions connecting the infection-free steady state E0 and the infection steady state E* by constructing a pair of upper-lower solutions. At last, numerical simulations are presented to confirm theoretical findings.

  10. A Model to Explain Temperature Dependent Systemic Infection of Potato Plants by Potato virus Y

    PubMed Central

    Choi, Kyung San; del Toro, Francisco; Tenllado, Francisco; Canto, Tomas; Chung, Bong Nam

    2017-01-01

    The effect of temperature on the rate of systemic infection of potatoes (Solanum tuberosum L. cv. Chu-Baek) by Potato virus Y (PVY) was studied in growth chambers. Systemic infection of PVY was observed only within the temperature range of 16°C to 32°C. Within this temperature range, the time required for a plant to become infected systemically decreased from 14 days at 20°C to 5.7 days at 28°C. The estimated lower thermal threshold was 15.6°C and the thermal constant was 65.6 degree days. A systemic infection model was constructed based on experimental data, using the infection rate (Lactin-2 model) and the infection distribution (three-parameter Weibull function) models, which accurately described the completion rate curves to systemic infection and the cumulative distributions obtained in the PVY-potato system, respectively. Therefore, this model was useful to predict the progress of systemic infections by PVY in potato plants, and to construct the epidemic models. PMID:28381967

  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. Modeling the Potential Impact of Vaccination on the Epidemiology of Congenital Cytomegalovirus Infection

    PubMed Central

    Lanzieri, Tatiana M.; Bialek, Stephanie R.; Ortega-Sanchez, Ismael R.; Gambhir, Manoj

    2016-01-01

    Background Understanding the potential for vaccination to change cytomegalovirus (CMV) epidemiology is important for developing CMV vaccines and designing clinical trials. Methods We constructed a deterministic, age-specific and time-dependent mathematical model of pathogen transmission, parameterized using CMV seroprevalence from the United States and Brazil, to predict the impact of vaccination on congenital CMV infection. Findings Concurrent vaccination of young children and adolescents would result in the greatest reductions in congenital CMV infections in populations with moderate and high baseline maternal seroprevalence. Such a vaccination strategy, assuming 70% vaccine efficacy, 90% coverage and 5-year duration of protection, could ultimately prevent 30%-50% of congenital CMV infections. At equilibrium, this strategy could result in a 30% reduction in congenital CMV infections due to primary maternal infection in the United States but a 3% increase in Brazil. The potential for an increase in congenital CMV infections due to primary maternal infections in Brazil was not predicted with use of a vaccine that confers protection for greater than 5 years. Interpretation Modeling suggests that vaccination strategies that include young children will result in greater declines in congenital CMV infection than those restricted to adolescents or women of reproductive age. Our study highlights the critical need for better understanding of the relative contribution of type of maternal infection to congenital CMV infection and disease, the main focus of vaccine prevention. PMID:24837782

  13. Gorham's disease of the mandible mimicking periodontal disease on radiograph.

    PubMed

    Mignogna, Michele Davide; Fedele, Stefano; Lo Russo, Lucio; Lanza, Alessandro; Marenzi, Gaetano; Sammartino, Gilberto

    2005-09-01

    Gorham's disease is a rare disorder characterized by spontaneous and progressive osteolysis of one or more skeletal bones. The radiographic findings associated with Gorham's disease are particularly dramatic, as in some cases a complete resorption of the involved bone can occur, leading to the definition of phantom bone, vanishing bone, or disappearing bone disease. A 24-year-old female patient with a previous diagnosis of periodontal disease and progressive mandibular alveolar bone loss was referred to our Oral Medicine section. The initial radiographic picture showed infrabony defects and horizontal bone loss. After further extensive local and systemic evaluation, including histopathological, laboratory and imagine techniques investigations, the patient was diagnosed to be affected by Gorham's disease. Meanwhile the progression of the osteolytic process had caused the loosening of all the left mandibular teeth and a pathologic fracture. Appropriate medical therapy was successful in stabilizating the resorptive process, with no evidence of further progressive disease. When Gorham's disease involves the mandible, the role of the periodontologist is extremely important in diagnosing promptly the disorder and preventing the functional and aesthetic consequences of advanced and extensive bone loss. Gorham's disease should be included among the pathologic entities mimicking periodontal disease on radiograph, such as inflammatory disease (e.g. osteomyelitis), endocrine disease (e.g. hyperparathyroidism), intra-osseous malignancies or metastases, lymphoma, histiocytosis X, mainly eosinophilic granuloma, infective process (e.g. tuberculosis and actinomycosis), odontogenic tumours.

  14. Retroperitoneal Cystic Malignant Fibrous Histiocytoma Mimicking a Psoas Abscess

    PubMed Central

    Gupta, Madan Mohan; Bahri, Nandini; Watal, Pankaj; Rathod, Ketan; Thaker, Siddarth; Bhandari, Parthiv; Dhamecha, Ketul; Ajudia, Jasmin

    2015-01-01

    Primary neoplasms in the psoas muscle including schwannoma and soft tissue sarcoma with secondary cystic degeneration are rare entities. They are difficult to distinguish from psoas abscess purely based on radiological findings. Malignant fibrous histiocytoma (MFH) in the retroperitoneum is an uncommon entity in contrast to liposarcoma and leiomyosarcoma. Psoas abscess is a common infection in the retroperitoneum, especially in regions where tuberculosis is endemic. In the current case, the patient presented with gradually progressive lower abdominal pain and raised erythrocyte sedimentation rate (ESR), lymphocyte count and sputum positive for acid fast bacilli. There was a presence of previous history of skeletal tuberculosis. Imaging revealed well-defined multilocular cystic lesion involving the left psoas muscle which along with the clinical scenario suggested psoas abscess. However, post-operative biopsy showed the lesion to be a MFH with extensive cystic degeneration. To the best of our knowledge, cystic MFH mimicking an abscess has been previously reported only once in an oncology literature. PMID:26557275

  15. Experimental Infection of Dogs with Leishmania and Saliva as a Model to Study Canine Visceral Leishmaniasis

    PubMed Central

    Costa, Dirceu Joaquim; Carvalho, Rayssa M. de Araujo; Abbehusen, Melissa; Teixeira, Clarissa; Pitombo, Maiana; Trigo, Joelma; Nascimento, Flávia; Amorim, Lucilene; Abreu-Silva, Ana Lucia; do Socorro Pires Cruz, Maria; Miranda, José Carlos; Fukutani, Kyoshi; de Oliveira, Camila I.; Barral, Aldina; Barral-Netto, Manoel; Brodskyn, Cláudia

    2013-01-01

    Background Canine Visceral Leishmaniasis (CVL) is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. Methodology/Principal Findings In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH) of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×107 parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×105 parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. Conclusion The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission. PMID:23577121

  16. 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

  17. Construction: a model program for infection control compliance.

    PubMed

    Kidd, Francine; Buttner, Clark; Kressel, Amy B

    2007-06-01

    In the 21st century, one of the most challenging tasks for the infection control practitioner (ICP) is establishing collegiality and trust with contractors, architects, maintenance and engineering personnel. We describe how an urban teaching hospital's infection control program cooperated with contractors during a large demolition, construction, and renovation project in order to protect its large population of immunosuppressed patients. Most contractors are not accustomed to taking special precautions during demolition. Because of a previous Aspergillus outbreak in our heart transplant population, we already had an established infection control (IC) training program for contractors. We expanded and codified it in response to a major hospital renovation. The IC, in-house Design and Construction, and outside contractors meet before the initiation of all major renovation projects to anticipate IC concerns and proactively plan for infection control interventions. Now, all contractors and maintenance staff are required to receive IC training at the time of their employment. A hospital identification badge with attached sticker that indicates the IC training date is required. Infection Control Risk Assessments (ICRA) are initiated by project managers and completed jointly with IC. The ICPs make rounds on all projects at least weekly and large projects are visited daily. We established a team comprised of ICP, project manager, construction manager, and area nurse manager to monitor and make recommendations for improvement continually during the project. Staff are educated about construction so they can help monitor airflow and cleanliness. Our contractors are more compliant with our IC specifications since they now understand why we insist on them. Through the years of major construction, the workers have jumped on the bandwagon. It is not unusual for construction or maintenance staff to contact IC for advice. There were four years of extensive construction without any

  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. Application of the diffusion-convection equation to modeling the infection by histoplasma-capsulatum

    NASA Astrophysics Data System (ADS)

    Jaime, Sergio A.

    2013-05-01

    Using computer algebra, the respiratory infection of the histoplasma capsulatum fungus was modeled and analyzed; the effects of the infection could also be described as a change in the lungs capacity to expand (associated with its elastic modulus). A further analysis to the immune system was also done in order to describe and model the way the body can handle those kinds of infections once they are hosted in the body. Using those models we can describe the behavior of the respiratory infection and then how to reduce or control its effects. As an investigation in the medical field, we need to test the models obtained and compare the results with the real infection behavior. The models where made based on the diffusive-convective equation; giving some initial and boundary conditions, we can get to the results obtained, which can describe how the infection is spreading and with a previous study of the immune system, the infection control done by the body can also be modeled.

  20. Foreign Body Infection Models to Study Host-Pathogen Response and Antimicrobial Tolerance of Bacterial Biofilm

    PubMed Central

    Nowakowska, Justyna; Landmann, Regine; Khanna, Nina

    2014-01-01

    The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI) animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials. PMID:27025752

  1. 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 mem