scholarly journals Candida albicanswhite and opaque cells exhibit distinct spectra of organ colonization in mouse models of infection

2018 ◽  
Author(s):  
Julie Takagi ◽  
Sheena D. Singh-Babak ◽  
Matthew B. Lohse ◽  
Chiraj K. Dalal ◽  
Alexander D. Johnson
Keyword(s):  
Candida Albicans ◽  
Animal Studies ◽  
Murine Models ◽  
Gi Tract ◽  
Internal Organs ◽  
Mucosal Surfaces ◽  
Default State ◽  
Serious Disease ◽  
First Time ◽  
Organ Colonization

AbstractCandida albicans, a species of fungi, can thrive in diverse niches of its mammalian hosts; it is a normal resident of the GI tract and mucosal surfaces but it can also enter the bloodstream and colonize internal organs causing serious disease. The ability ofC. albicansto thrive in these different host environments has been attributed, at least in part, to its ability to assume different morphological forms. In this work, we examine one such morphological change known as white-opaque switching. White cells are the default state ofC. albicans, and most animal studies have been carried out exclusively with white cells. Here, we compared the proliferation of white and opaque cells in two murine models of infection and also monitored, using specially constructed strains, switching between the two states in the host. We found that white cells outcompeted opaque cells in many niches; however, we show for the first time that in some organs (specifically, the heart and spleen), opaque cells competed favorably with white cells and, when injected on their own, could colonize these organs. In environments where the introduced white cells outcompeted the introduced opaque cells, we observed high rates of opaque-to-white switching. We did not observe white-to-opaque switching in any of the niches we examined.

scholarly journals CX3CR1 Is Dispensable for Control of Mucosal Candida albicans Infections in Mice and Humans

2014 ◽  
Vol 83 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Timothy J. Break ◽  
Martin Jaeger ◽  
Norma V. Solis ◽  
Scott G. Filler ◽  
Carlos A. Rodriguez ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Human Population ◽  
Systemic Candidiasis ◽  
Gi Tract ◽  
Content Type ◽  
Commensal Microbiota ◽  
Interleukin 17A ◽  
Mucosal Surfaces ◽  
Bacterial Microbiota ◽  
Mucosal Candidiasis

Candida albicansis part of the normal commensal microbiota of mucosal surfaces in a large percentage of the human population. However, perturbations of the host's immune response or bacterial microbiota have been shown to predispose individuals to the development of opportunisticCandidainfections. It was recently discovered that a defect in the chemokine receptor CX3CR1 increases susceptibility of mice and humans to systemic candidiasis. However, whether CX3CR1 confers protection against mucosalC. albicansinfection has not been investigated. Using two different mouse models, we found that Cx3cr1 is dispensable for the induction of interleukin 17A (IL-17A), IL-22, and IL-23 in the tongue after infection, as well as for the clearance of mucosal candidiasis from the tongue or lower gastrointestinal (GI) tract colonization. Furthermore, the dysfunctional human CX3CR1 alleleCX3CR1-M280was not associated with development of recurrent vulvovaginal candidiasis (RVVC) in women. Taken together, these data indicate that CX3CR1 is not essential for protection of the host against mucosal candidiasis, underscoring the dependence on different mammalian immune factors for control of mucosal versus systemicCandidainfections.

scholarly journals Murine Models of Candida Gastrointestinal Colonization and Dissemination

2013 ◽  
Vol 12 (11) ◽  
pp. 1416-1422 ◽  
Author(s):  
Andrew Y. Koh
Keyword(s):  
Infectious Agents ◽  
Murine Models ◽  
Gi Tract ◽  
Future Directions ◽  
Content Type ◽  
Animal Modeling ◽  
Mucosal Surfaces ◽  
Modeling Systems ◽  
Human Infections ◽  
Gastrointestinal Colonization

ABSTRACTNinety-five percent of infectious agents enter through exposed mucosal surfaces, such as the respiratory and gastrointestinal (GI) tracts. The human GI tract is colonized with trillions of commensal microbes, including numerousCandidaspp. Some commensal microbes in the GI tract can cause serious human infections under specific circumstances, typically involving changes in the gut environment and/or host immune conditions. Therefore, utilizing animal models of fungal GI colonization and dissemination can lead to significant insights into the complex pathophysiology of transformation from a commensal organism to a pathogen and host-pathogen interactions. This paper will review the methodologic approaches used for modeling GI colonization versus dissemination, the insights learned from these models, and finally, possible future directions using these animal modeling systems.

scholarly journals Candida Albicans Virulence Factors and Its Pathogenicity

2021 ◽  
Vol 9 (4) ◽  
pp. 704
Author(s):  
Mariana Henriques ◽  
Sónia Silva
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Healthy Individuals ◽  
Mucosal Surfaces

Candida albicans lives as commensal on the skin and mucosal surfaces of the genital, intestinal, vaginal, urinary, and oral tracts of 80% of healthy individuals [...]

scholarly journals Magnets and self-retractable wire for endoscopic septotomies: From concept to first-in-human use.

Endoscopy ◽  
2021 ◽  
Author(s):  
François Huberland ◽  
Ricardo Rio Tinto ◽  
Sonia Dugardeyn ◽  
Nicolas Cauche ◽  
Cécilia Delattre ◽  
...  
Keyword(s):  
Animal Studies ◽  
Unmet Needs ◽  
Previous Knowledge ◽  
Esophageal Diverticulum ◽  
Gi Tract ◽  
Single Procedure ◽  
Compression Anastomosis ◽  
Human Use ◽  
Epiphrenic Esophageal Diverticulum ◽  
Safe Performance

Background and study aims: A medical device that allows simple and safe performance of an endoscopic septotomy could have several applications in the gastrointestinal (GI) tract. We developed such a device by combining two magnets and a self-retractable wire to perform a progressive septotomy by compression of the tissues. We describe here the concept, preclinical studies, and first clinical use of the device in symptomatic epiphrenic esophageal diverticulum (EED). Materials and methods: The MAGUS was designed based on previous knowledge of compression anastomosis and current unmet needs. After initial design, the feasibility of the technique was tested on artificial septa in pigs. A clinical trial was then initiated to assess the feasibility and safety of the technique. Results: Animal studies showed that the MAGUS can perform a complete septotomy at various levels of the GI tract. In two patients with symptomatic EED, uneventful complete septotomy was observed within 28 and 39 days after the endoscopic procedure. Conclusions: This new system provides a way to perform endoluminal septotomy in a single procedure. It appears to be effective and safe for managing symptomatic EED. Further clinical applications where this type of remodeling of the GI tract could be beneficial are under investigation.

scholarly journals Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

2021 ◽  
Vol 22 (5) ◽  
pp. 2479
Author(s):  
Amir Mohammadzadeh ◽  
Péter P. Lakatos ◽  
Mihály Balogh ◽  
Ferenc Zádor ◽  
Dávid Árpád Karádi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Studies ◽  
Acute Administration ◽  
Pain Model ◽  
Therapeutic Value ◽  
Small Doses ◽  
Function Test ◽  
Neuropathic Pain Model ◽  
First Time ◽  
Glycine Content

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.

scholarly journals The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile

2020 ◽  
Vol 10 (1) ◽  
pp. 96
Author(s):  
Andrew M. Skinner ◽  
S. Tyler Phillips ◽  
Michelle M. Merrigan ◽  
Kevin J. O’Leary ◽  
Susan P. Sambol ◽  
...  
Keyword(s):  
Animal Studies ◽  
Specific Treatment ◽  
Restriction Endonuclease Analysis ◽  
Natural Occurrence ◽  
Relative Role ◽  
Intestinal Epithelial ◽  
Large Molecular Weight ◽  
Stool Samples ◽  
Serious Disease ◽  
Isogenic Mutants

Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While initial studies of purified toxins in animal models pointed to toxin A (TcdA) as the main virulence factor, animal studies using isogenic mutants demonstrated that toxin B (TcdB) alone was sufficient to cause disease. In addition, the natural occurrence of TcdA−/TcdB+ (TcdA−/B+)mutant strains was shown to be responsible for cases of C. difficile infection (CDI) with symptoms identical to CDI caused by fully toxigenic (A+/B+) strains. Identification of these cases was delayed during the period when clinical laboratories were using immunoassays that only detected TcdA (toxA EIA). Our hospital laboratory at the time performed culture as well as toxA EIA on patient stool samples. A total of 1.6% (23/1436) of all clinical isolates recovered over a 2.5-year period were TcdA−/B+ variants, the majority of which belonged to the restriction endonuclease analysis (REA) group CF and toxinotype VIII. Despite reports of serious disease due to TcdA−/B+ CF strains, these infections were typically mild, often not requiring specific treatment. While TcdB alone may be sufficient to cause disease, clinical evidence suggests that both toxins have a role in disease.

MICROSCOPIC CHANGES IN THE INTERNAL ORGANS OF WHITE MICE DURING EXPERIMENTAL IRON (IV) CLATHROCHELATE TOXICOSIS

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  
Keyword(s):  
Biological Response ◽  
Organ Damage ◽  
The Body ◽  
New Drugs ◽  
Laboratory Animals ◽  
Internal Organs ◽  
Experimental Drug ◽  
Liver And Kidney ◽  
Preclinical And Clinical Studies ◽  
First Time

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.

scholarly journals Oral candidiasis-adhesion of non-albicans Candida species

2008 ◽  
pp. 69-78 ◽  
Author(s):  
Marija Bokor-Bratic
Keyword(s):  
Candida Albicans ◽  
Candida Species ◽  
Oral Candidiasis ◽  
Initial Step ◽  
Oral Microflora ◽  
Mucosal Surfaces ◽  
Buccal Epithelial Cells ◽  
Mucosal Infection ◽  
Denture Acrylics ◽  
Candida Colonisation

Oral candidiasis is an opportunistic infection caused primarily by Candida albicans. However, in recent years, species of non-albicans Candida have been implicated more frequently in mucosal infection. Candida species usually reside as commensal organisms and are part of normal oral microflora. Determining exactly how transformation from commensal to pathogen takes place and how it can be prevented is continuous challenge for clinical doctors. Candidal adherence to mucosal surfaces is considered as a critical initial step in the pathogenesis of oral candidiasis. Acrylic dentures, acting as reservoirs, play an important role in increasing the risk from Candida colonisation. Thus, this review discusses what is currently known about the adhesion of non-albicans Candida species of oral origin to buccal epithelial cells and denture acrylics.

scholarly journals PROFIL KANDIDIASIS VULVOVAGINALIS DI POLIKLINIK KULIT DAN KELAMIN RSUP PROF. DR. R. D. KANDOU MANADO PERIODE JANUARI – DESEMBER 2013

e-CliniC ◽  
2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Novita Limbu Tasik ◽  
Grace M. Kapantow ◽  
Renate T. Kandou
Keyword(s):  
Candida Albicans ◽  
Combination Therapy ◽  
Medical Record ◽  
Vaginal Discharge ◽  
Age Groups ◽  
Descriptive Study ◽  
Reproductive Organs ◽  
Frequent Type ◽  
First Time ◽  
Female Reproductive Organs

Abstract: Vulvovaginalis candidiasis (VVC) is a disease of female reproductive organs with the site of infection at the vulva and vagina mucosa characterized by vaginal discharge and itching due to the uncontrolled growth of the fungus Candida albicans. This study aimed to obtain the profile of vulvovaginalis candidiasis cases at Prof. Dr. R. D. Kandou Hospiptal Manado from January to December 2013. This was a retrospective descriptive study using the medical record. The results showed that of 29 VVC cases (0.70%), the largest age groups were 15-24 and 25-44 years (41.4%). Housewives and students were the most found jobs (20.7%). The discharge accompanied by itching was found in 34.5% of cases. The use of douching and pregnancy were predisposing factors (13.8%). Gram examinations resulted in spores, budding cell, and pseudohyphae were found in 62.1% of cases. Patients who was infected by VVC for the first time were 82.8%. The most frequent type of therapy was combination therapy (48.3%). Keywords: vulvovaginalis candidiasis   Abstrak: Kandidiasis vulvovaginalis (KVV) merupakan suatu penyakit organ reproduksi pada wanita dimana terjadi infeksi pada mukosa vulva dan vagina ditandai dengan adanya keputihan dan gatal dikarenakan pertumbuhan tidak terkendali dari jamur Candida albicans. Penelitian ini bertujuan untuk mengetahui profil pasien kandidiasis vulvovaginalis di RSUP Prof. Dr. R. D. Kandou Manado periode Januari – Desember 2013. Penelitian ini bersifat deskriptif retrospektif dengan mengevaluasi catatan rekam medik pasien. Hasil penelitian menunjukkan terdapat 29 kasus KVV. Kelompok umur terbanyak 15-24 dan 25-44 tahun (41,4%); pekerjaan terbanyak ialah ibu rumah tangga dan pelajar (20,7%); keputihan disertai gatal (34,5%); faktor predisposisi terbanyak yaitu penggunaan douching dan kehamilan (13.8%). Pemeriksaan Gram ditemukan spora, buddingcell dan pseudohifa ditemukan pada 62,1% kasus. Pasien yang baru pertama kali terinfeksi KVV  sebanyak 82,8%. Jenis terapi terbanyak yang diberikan yaitu terapi kombinasi sebanyak 48,3%). Kata kunci: kandidiasis vulvovaginalis

scholarly journals Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2116
Author(s):  
Marija Geroldinger-Simić ◽  
Thomas Bögl ◽  
Markus Himmelsbach ◽  
Norbert Sepp ◽  
Wolfgang Buchberger
Keyword(s):  
Systemic Sclerosis ◽  
High Performance ◽  
Clinical Manifestations ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Internal Organs ◽  
New Biomarkers ◽  
First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

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