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Article: Protocols for vaginal inoculation and sample collection in the experimental mouse model of Candida vaginitis

Yano, Junko / Fidel, Jr., Paul L

Journal of visualized experiments. 2011 Dec. 08, , no. 58

2011

Abstract: Vulvovaginal candidiasis (VVC), caused by Candida species, is a fungal infection of the lower female genital tract that affects approximately 75% of otherwise healthy women during their reproductive years18,32-34. Predisposing factors include antibiotic ... ...

Abstract	Vulvovaginal candidiasis (VVC), caused by Candida species, is a fungal infection of the lower female genital tract that affects approximately 75% of otherwise healthy women during their reproductive years18,32-34. Predisposing factors include antibiotic usage, uncontrolled diabetes and disturbance in reproductive hormone levels due to pregnancy, oral contraceptives or hormone replacement therapies33,34. Recurrent VVC (RVVC), defined as three or more episodes per year, affects a separate 5 to 8% of women with no predisposing factors33. An experimental mouse model of VVC has been established and used to study the pathogenesis and mucosal host response to Candida3,4,11,16,17,19,21,25,37. This model has also been employed to test potential antifungal therapies in vivo13,24. The model requires that the animals be maintained in a state of pseudoestrus for optimal Candida colonization/infection6,14,23. Under such conditions, inoculated animals will have detectable vaginal fungal burden for weeks to months. Past studies show an extremely high parallel between the animal model and human infection relative to immunological and physiological properties3,16,21. Differences, however, include a lack of Candida as normal vaginal flora and a neutral vaginal pH in the mice. Here, we demonstrate a series of key methods in the mouse vaginitis model that include vaginal inoculation, rapid collection of vaginal specimens, assessment of vaginal fungal burden, and tissue preparations for cellular extraction/isolation. This is followed by representative results for constituents of vaginal lavage fluid, fungal burden, and draining lymph node leukocyte yields. With the use of anesthetics, lavage samples can be collected at multiple time points on the same mice for longitudinal evaluation of infection/colonization. Furthermore, this model requires no immunosuppressive agents to initiate infection, allowing immunological studies under defined host conditions. Finally, the model and each technique introduced here could potentially give rise to use of the methodologies to examine other infectious diseases of the lower female genital tract (bacterial, parasitic, viral) and respective local or systemic host defenses.
Keywords	Candida ; anesthetics ; animal models ; antibiotics ; diabetes ; female genitalia ; flora ; fungi ; human diseases ; immunosuppressive agents ; leukocytes ; lymph nodes ; mice ; oral contraceptives ; pH ; pathogenesis ; pregnancy ; vaginitis ; vulvovaginal candidiasis ; women
Language	English
Dates of publication	2011-1208
Size	p. e3382.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/3382
Database	NAL-Catalogue (AGRICOLA)

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Article: Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

Yano, Junko / Noverr, Mairi C / Fidel, Paul L., Jr

Cytokine. 2012 Apr., v. 58, no. 1

2012

Abstract: Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to ... ...

Abstract	Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4⁺ T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators.
Keywords	Candida albicans ; T-lymphocytes ; adaptive immunity ; animal models ; animals ; candidiasis ; chemotaxis ; cytokines ; defense mechanisms ; epithelial cells ; fungi ; immunosuppression (physiological) ; inflammation ; neutrophils ; vaginitis ; women
Language	English
Dates of publication	2012-04
Size	p. 118-128.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2011.11.021
Database	NAL-Catalogue (AGRICOLA)

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Article: Animal models of mucosal Candida infection

Naglik, Julian R / Fidel, Paul L. Jr / Odds, Frank C

FEMS microbiology letters. 2008 June, v. 283, no. 2

2008

Abstract: Rodent models of oral, vaginal and gastrointestinal Candida infection are described and discussed in terms of their scientific merits. The common feature of all experimental mucosal Candida infections is the need for some level of host immunocompromise ... ...

Abstract	Rodent models of oral, vaginal and gastrointestinal Candida infection are described and discussed in terms of their scientific merits. The common feature of all experimental mucosal Candida infections is the need for some level of host immunocompromise or exogenous treatment to ensure quantitatively reproducible disease. A growing literature describes the contributions of such candidiasis models to our understanding of certain aspects of fungal virulence and host response to mucosal Candida albicans challenge. Evidence to date shows that T-lymphocyte responses dominate host immune defences to oral and gastrointestinal challenge, while other, highly compartmentalized responses defend vaginal surfaces. By contrast the study of C. albicans virulence factors in mucosal infection models has only begun to unravel the complex of attributes required to define the difference between strongly and weakly muco-invasive strains.
Keywords	epithelium ; animals ; models
Language	English
Dates of publication	2008-06
Size	p. 129-139.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1111/j.1574-6968.2008.01160.x
Database	NAL-Catalogue (AGRICOLA)

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Article: Epithelial Cell-Derived S100 Calcium-Binding Proteins as Key Mediators in the Hallmark Acute Neutrophil Response during Candida Vaginitis

Yano, Junko / Lilly, Elizabeth / Barousse, Melissa / Fidel, Paul L. Jr

Infection and immunity. 2010 Dec., v. 78, no. 12

2010

Abstract: Vulvovaginal candidiasis (VVC), caused by Candida species, is a significant problem in women of childbearing age. Similar to clinical observations, a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in a subset of mice without affecting ...

Abstract	Vulvovaginal candidiasis (VVC), caused by Candida species, is a significant problem in women of childbearing age. Similar to clinical observations, a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in a subset of mice without affecting vaginal fungal burden. We hypothesize that the vaginal PMN infiltrate and accompanying inflammation are not protective but instead are responsible for the symptoms of infection. The purpose of this study was to identify the signal(s) associated with the PMN response in the established mouse model. Vaginal lavage fluid from inoculated mice were categorized base on PMN counts, evaluated for PMN chemotactic activity and analyzed by SDS-PAGE and mass spectrometry (MS) for unique protein identification. The lavage fluid from inoculated mice with high, but not low, PMN levels showed increased chemotactic activity. Likewise, SDS-PAGE of lavage fluid with high PMN levels showed distinct protein patterns. MS revealed that bands at 6 and 14 kDa matched the PMN chemotactic calcium-binding proteins (CBPs), S100A8 and S100A9, respectively. The presence of the CBPs in lavage fluid was confirmed by Western blots and enzyme-linked immunosorbent assay. Vaginal tissues and epithelial cells from inoculated mice with high PMN levels stained more intensely and exhibited increased mRNA transcripts for both proteins compared to those in mice with low PMN levels. Subsequent antibody neutralization showed significant abrogation of the chemotactic activity when the lavage fluid was treated with anti-S100A8, but not anti-S100A9, antibodies. These results reveal that the PMN chemotactic CBP S100A8 and S100A9 are produced by vaginal epithelial cells following interaction with Candida and that S100A8 is a strong candidate responsible for the robust PMN migration during experimental VVC.
Keywords	Candida ; animal models ; antibodies ; calcium-binding proteins ; candidiasis ; chemotaxis ; enzyme-linked immunosorbent assay ; epithelial cells ; fungi ; inflammation ; mass spectrometry ; messenger RNA ; mice ; neutralization ; polyacrylamide gel electrophoresis ; vaginitis ; women
Language	English
Size	p. 5126-5137.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 684: Show issues

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Article ; Online: Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection.

Aguirre-Botero, Manuela C / Wang, Lawrence T / Formaglio, Pauline / Aliprandini, Eduardo / Thiberge, Jean-Michel / Schön, Arne / Flores-Garcia, Yevel / Mathis-Torres, Shamika / Flynn, Barbara J / da Silva Pereira, Lais / Le Duff, Yann / Hurley, Mathew / Nacer, Adéla / Bowyer, Paul W / Zavala, Fidel / Idris, Azza H / Francica, Joseph R / Seder, Robert A / Amino, Rogerio

Cell reports

2023 Volume 42, Issue 7, Page(s) 112681

Abstract: Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using ... ...

Abstract	Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using 13 distinctive PfCSP hmAbs, we provide a comprehensive view of how PfCSP hmAbs neutralize sporozoites in host tissues. Sporozoites are most vulnerable to hmAb-mediated neutralization in the skin. However, rare but potent hmAbs additionally neutralize sporozoites in the blood and liver. Efficient protection in tissues mainly associates with high-affinity and high-cytotoxicity hmAbs inducing rapid parasite loss-of-fitness in the absence of complement and host cells in vitro. A 3D-substrate assay greatly enhances hmAb cytotoxicity and mimics the skin-dependent protection, indicating that the physical stress imposed on motile sporozoites by the skin is crucial for unfolding the protective potential of hmAbs. This functional 3D cytotoxicity assay can thus be useful for downselecting potent anti-PfCSP hmAbs and vaccines.
MeSH term(s)	Animals ; Humans ; Plasmodium falciparum ; Malaria Vaccines ; Malaria ; Protozoan Proteins ; Immunoglobulins ; Sporozoites ; Malaria, Falciparum
Chemical Substances	Malaria Vaccines ; Protozoan Proteins ; Immunoglobulins
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112681
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Animal models of mucosal Candida infection.

Naglik, Julian R / Fidel, Paul L / Odds, Frank C

FEMS microbiology letters

2008 Volume 283, Issue 2, Page(s) 129–139

Abstract	Rodent models of oral, vaginal and gastrointestinal Candida infection are described and discussed in terms of their scientific merits. The common feature of all experimental mucosal Candida infections is the need for some level of host immunocompromise or exogenous treatment to ensure quantitatively reproducible disease. A growing literature describes the contributions of such candidiasis models to our understanding of certain aspects of fungal virulence and host response to mucosal Candida albicans challenge. Evidence to date shows that T-lymphocyte responses dominate host immune defences to oral and gastrointestinal challenge, while other, highly compartmentalized responses defend vaginal surfaces. By contrast the study of C. albicans virulence factors in mucosal infection models has only begun to unravel the complex of attributes required to define the difference between strongly and weakly muco-invasive strains.
MeSH term(s)	Animals ; Candida albicans/immunology ; Candida albicans/pathogenicity ; Candidiasis, Oral/immunology ; Candidiasis, Oral/microbiology ; Candidiasis, Vulvovaginal/immunology ; Candidiasis, Vulvovaginal/microbiology ; Disease Models, Animal ; Female ; Gastrointestinal Diseases/immunology ; Gastrointestinal Diseases/microbiology ; Host-Pathogen Interactions ; Intestinal Mucosa/immunology ; Intestinal Mucosa/microbiology ; Rodentia ; T-Lymphocytes/immunology ; Virulence Factors/physiology
Chemical Substances	Virulence Factors
Language	English
Publishing date	2008-04-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1111/j.1574-6968.2008.01160.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: Analysis of measles-mumps-rubella (MMR) titers of recovered COVID-19 patients

Gold, Jeffrey / Baumgartl, William / Okyay, Ramazan / Licht, Warren / Fidel, Jr., Paul / Noverr, Mairi / Tilley, Larry / Hurley, David / Rada, Balázs / Ashford, John

2020

Abstract: The measles-mumps-rubella (MMR) vaccine has been theorized to provide protection against COVID-19. Our aim was to determine whether any MMR IgG titers are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with MMR II. ...

Abstract	The measles-mumps-rubella (MMR) vaccine has been theorized to provide protection against COVID-19. Our aim was to determine whether any MMR IgG titers are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with MMR II. We divided 80 subjects into two groups, comparing MMR titers to recent COVID-19 severity. The MMR II group consisted of 50 subjects who would primarily have MMR antibodies from the MMR II vaccine, and a comparison group of 30 subjects who would primarily have MMR antibodies from sources other than MMR II, including prior measles, mumps, and/or rubella illnesses. There was a significant inverse correlation (rs = -0.71, P < .001) between mumps titers and COVID-19 severity within the MMR II group. There were no correlations between mumps titers and severity in the comparison group, between mumps titers and age in the MMRII group, or between severity and measles or rubella titers in either group. Within the MMR II group: mumps titers of 134 to 300 AU/ml (n=8) were only found in those who were functionally immune or asymptomatic; all with mild symptoms had mumps titers below 134 AU/ml (n=17); all with moderate symptoms had mumps titers below 75 AU/ml (n=11); all who had been hospitalized and required oxygen had mumps titers below 32 AU/ml (n=5). Our results demonstrate that there is a significant inverse correlation between mumps titers from MMR II and COVID-19 severity. Study Design. MMR IgG titers were measured in 80 adults consented to join our study. All were born in the United States and over 18 years of age. Applicants (n=568) were screened using a HIPAA-compliant online form in which informed consent was obtained, approved by our Investigational Review Board (Integrity IRB Protocol ID: 40005). Subjects were chosen from applicants who responded to online advertisements that we ran seeking recovered COVID-19 patients for this study. Each applicant was required to upload documentation of their COVID-19 medical history including COVID-19 test results and hospitalization records, as well as completing an in-depth online survey in which they provided details related to their COVID-19 symptoms and outcomes on a HIPAA-compliant form. Follow-up was done as necessary to verify the information provided to ensure each subject met the study criteria. Subjects in the study were selected in the order that they applied, if they matched criteria for either the MMR II group or the comparison group, until all 80 subjects had been selected and tested. Review of applicants stopped once 80 subjects had been selected. The selection and titer test process ran from May 12, 2020 through August 26, 2020. A small stipend to help defray costs was available to subjects. We divided subjects into two groups. The first group was the MMR II group which consisted of 50 subjects (mean age, 30.6 [SD, 7.6], 33 women, 17 men) whose only likely source of MMR antibodies would be from the MMR II vaccine. Of these, 40 had previously tested COVID-19 positive with symptoms ranging from asymptomatic to requiring a ventilator, and 10 subjects were functionally immune (COVID-19 negative despite strong COVID-19 exposure). Functionally immune subjects had several days of close contact with someone who was symptomatic and who had tested positive for COVID-19, without either person social distancing or wearing masks. Despite the extensive contact, the functionally immune subjects tested negative for COVID-19 and never exhibited symptoms. Each person in the MMR II group was U.S. born and either: born on or after December 1, 1978, meaning they would have received their first vaccination after the MMR II vaccine was launched; or if born on or after December 1, 1973 but before December 1, 1978, specifically documented one or more MMR II vaccinations. The remaining 30 subjects (mean age, 57.4 [SD, 7.8], 18 women, 12 men) made up the comparison group, all of whom tested positive for COVID-19 and were born before December 1, 1976. All subjects in the comparison group were born at least several years before the MMR II vaccine was launched, and none had any record of ever receiving an MMR II vaccination or booster. The age disparity between the MMR II group and the comparison group was purposeful, which is why we utilized a comparison group, not a control group. Age differentiation was the only way to accurately separate people who definitively had prior MMR II vaccinations from those who had not. Mumps, measles, and rubella IgG titers were measured by Quest Diagnostics using LIAISON analyzers with chemiluminescence immunoassay (CLIA) technology for the qualitative determination of IgG antibodies in human serum specimens. The method for qualitative determination of specific IgG to each virus was an indirect CLIA. The principal components of each test were magnetic particles (solid phase) coated with recombinant antigen and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, antibodies to the virus being tested present in the calibrators, specimens or controls would bind to the solid phase. During the second incubation, the antibody conjugate would react with each virus IgG already bound to the solid phase. After each incubation, the unbound material was removed with a wash cycle. Subsequently, the starter reagents were added and a flash chemiluminescence reaction was thus induced. The chemiluminescent signal, and hence the amount of isoluminol-antibody conjugate, was measured by a photomultiplier as relative light units (RLU) and was indicative of the presence of IgG in calibrators, specimens, or controls. Diagnostic sensitivities were: measles 94.7% (95% C.I.: 91.7-96.9%), mumps 98.5% (95% C.I.: 96.5-99.5%), rubella 100% (95% C.I.: 99.3-100%). Diagnostic specificities were: measles 97.4% (95% C.I.:94.1-99.2%), mumps 98.2% (95% C.I.: 94.8-99.6%), rubella 100% (95% C.I: 97.0-100%). Symptoms Score Calculations. Each subject began with a score of zero, then points were added. One point each: COVID-19 positive, dry cough, sore throat, slight shortness of breath, headache, confusion, muscle aches/pain, fever over 101° F, nausea and/or vomiting, or diarrhea. Two points each: severe difficulty breathing, chest pain, or sudden loss of sense of smell/taste. Five points each: subject was hospitalized, required supplemental oxygen, or was intubated on a ventilator. Severity Levels. Five severity levels were designated based upon symptoms scores. "Functionally Immune" had a symptom score of 0. "Asymptomatic" had a score of 1, i.e., those who were COVID-19 positive but had no symptoms. "Mild" were those with scores ranging from 2 to 10. "Moderate" were those with scores from 11 to 20. "Severe" were those with scores from 21 to 30.
Keywords	Coronavirus disease ; [ 360 ] COVID-19 ; Vaccination and immunization ; Measles virus ; MMR ; Mumps virus ; Rubella virus ; SARS-CoV-2 ; titers ; non-specific effects of vaccines ; innate and adaptive immunity ; covid19
Subject code	150
Publishing date	2020-09-28
Publishing country	eu
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Role for Dendritic Cells in Immunoregulation during Experimental Vaginal Candidiasis

LeBlanc, Dana M / Barousse, Melissa M / Fidel, Paul L. Jr

Infection and immunity. 2006 June, v. 74, no. 6

2006

Abstract: Vulvovaginal candidiasis (VVC) caused by the commensal organism Candida albicans remains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity ... ...

Abstract	Vulvovaginal candidiasis (VVC) caused by the commensal organism Candida albicans remains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity by CD4⁺ Th1-type cells is protective against most forms of mucosal candidiasis, no protective role for adaptive immunity has been identified against VVC. This is postulated to be due to immunoregulation that prohibits a more profound Candida-specific CD4⁺ T-cell response against infection. The purpose of this study was to examine the role of dendritic cells (DCs) in the induction phase of the immune response as a means to understand the initiation of the immunoregulatory events. Immunostaining of DCs in sectioned murine lymph nodes draining the vagina revealed a profound cellular reorganization with DCs becoming concentrated in the T-cell zone throughout the course of experimental vaginal Candida infection consistent with cell-mediated immune responsiveness. However, analysis of draining lymph node DC subsets revealed a predominance of immunoregulation-associated CD11c⁺ B220⁺ plasmacytoid DCs (pDCs) under both uninfected and infected conditions. Staining of vaginal DCs showed the presence of both DEC-205⁺ and pDCs, with extension of dendrites into the vaginal lumen of infected mice in close contact with CANDIDA: Flow cytometric analysis of draining lymph node DC costimulatory molecules and activation markers from infected mice indicated a lack of upregulation of major histocompatibility complex class II, CD80, CD86, and CD40 during infection, consistent with a tolerizing condition. Together, the results suggest that DCs are involved in the immunoregulatory events manifested during a vaginal Candida infection and potentially through the action of pDCs.
Keywords	Candida albicans ; candidiasis ; cell-mediated immunity ; dendrites ; dendritic cells ; flow cytometry ; immune response ; immunomodulation ; lymph nodes ; major histocompatibility complex ; mice ; vagina ; women
Language	English
Size	p. 3213-3221.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 684: Show issues

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Article: Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infection

Peters, Brian M / Zhu, Jingsong / Fidel, Paul L. Jr / Scheper, Mark A / Hackett, William / El Shaye, Sara / Jabra-Rizk, Mary Ann

FEMS yeast research. 2010 Aug., v. 10, no. 5

2010

Abstract: The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen ...

Abstract	The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide.
Keywords	Candida albicans ; immunity
Language	English
Dates of publication	2010-08
Size	p. 597-604.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1111/j.1567-1364.2010.00632.x
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 5454: Show issues

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Article ; Online: Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

Raman, Betty / Cassar, Mark Philip / Tunnicliffe, Elizabeth M / Filippini, Nicola / Griffanti, Ludovica / Alfaro-Almagro, Fidel / Okell, Thomas / Sheerin, Fintan / Xie, Cheng / Mahmod, Masliza / Mózes, Ferenc E / Lewandowski, Adam J / Ohuma, Eric O / Holdsworth, David / Lamlum, Hanan / Woodman, Myles J / Krasopoulos, Catherine / Mills, Rebecca / McConnell, Flora A Kennedy /

Wang, Chaoyue / Arthofer, Christoph / Lange, Frederik J / Andersson, Jesper / Jenkinson, Mark / Antoniades, Charalambos / Channon, Keith M / Shanmuganathan, Mayooran / Ferreira, Vanessa M / Piechnik, Stefan K / Klenerman, Paul / Brightling, Christopher / Talbot, Nick P / Petousi, Nayia / Rahman, Najib M / Ho, Ling-Pei / Saunders, Kate / Geddes, John R / Harrison, Paul J / Pattinson, Kyle / Rowland, Matthew J / Angus, Brian J / Gleeson, Fergus / Pavlides, Michael / Koychev, Ivan / Miller, Karla L / Mackay, Clare / Jezzard, Peter / Smith, Stephen M / Neubauer, Stefan

EClinicalMedicine

2021 Volume 31, Page(s) 100683

Abstract: Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.: Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, ... ...

Abstract	Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. Findings: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls ( Interpretation: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. Funding: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.
Language	English
Publishing date	2021-01-07
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2020.100683
Database	MEDical Literature Analysis and Retrieval System OnLINE

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