Oral Candida Infection Research Articles

Candidal Adhesion to an Oral Obturator PMMA Resin Incorporated with Vanillin

An oral obturator is a prosthesis used for a variety of dental conditions to help patients regain their abilities after trauma, surgeries, or having congenital defects. It is commonly made from polymethyl methacrylate (PMMA) resin. Despite that, this resin appliance can give rise to a condition for microbial adhesion and colonization on the resin surface itself and the mucosa beneath. This can place patients at a greater risk of infection. Oral infections caused by Candida species are found to be more common, particularly in immunologically compromised patients and those with other conditions in the oral cavity that often include oral prosthetic appliances. Obturator resin incorporated with vanillin has been produced and shown to have antimicrobial properties against some bacteria and yeasts. The purpose of this study was to determine the adhesion of candida to vanillin incorporated obturator resin. The auto-polymerized resin samples (Orthocryl® EQ, Dentaurum, Germany) were prepared with different concentrations of vanillin incorporation (0.1%, 0.5%, and 1% vanillin w/w). All samples were coated with sterile saliva and incubated at 37 °C for 60 min. The adhesion assay was done with four species of candida (C. albicans ATCC 10231, C. krusei ATCC 14243, C. glabrata ATCC 15126, and C. tropicalis ATCC 1369). The resin samples were placed in a 24-well plate containing 107 CFU/mL of candidal suspension and incubated in a shaking incubator (120 r/min) at 37°C for 2 h for candidal adhesion. Non-adherent cells were removed by washing with phosphate buffer saline (PBS) solution. The remaining adherent cells on the obturator resin surface were quantified by the WST Microbial Cell Counting Kit (Dojindo Molecular Technologies, USA). The Kruskal-Wallis test, followed by Dunn’s method, was applied for statistical analysis. The results showed that the addition of 0.5% and 1% w/w vanillin to oral obturator PMMA resin could significantly reduce the adhesion of all Candida species except that of C. krusei, for which a reduction effect was observed at 1 % vanillin. The percentage reduction of candidal adhesion on obturator resin varies from 9% to 35%, which was highest on C. albicans, followed by C. glabrata (24%), and C. tropicalis (21%). No reduction effect was observed at 0.1% vanillin on all Candida species. In conclusion, vanillin-incorporated oral obturator resin displayed a reducing effect on the adhesion of all tested Candida species. C. albicans was the most susceptible species, while C. krusei was the most resistant. The mechanisms of action could possibly be the aldehyde group of the vanillin structure that causes cell membrane damage, interferes with DNA, RNA, and protein synthesis, as well as enzyme activities within the yeast cell. This newly developed PMMA resin could be valuable for the prevention or as an adjunctive treatment for controlling oral candidal infection among patients who use oral obturators.

Low level of antifungal resistance in Candida species recovered from Iranian HIV-associated oral infection.

Oral candidiasis (OC) is the most frequent opportunistic fungal infection, which is a predictive indicator of immunosuppression and disease progression among people living with HIV/AIDS (PLWHA). In the present study, 109 Candida isolates were collected from 94 PLWHA afflicted with oral Candida infection (OCI) following highly active antiretroviral therapy (HAART). The susceptibility profiles of Candidaspp. to six antifungal agents were evaluated using CLSI broth microdilution. The prevalence of OCI was 34.06%. The susceptibility profile of Candidaspp. revealed 100% sensitivity to caspofungin, while 6.4%, 5.4%, 24.5%, and 2.8% of Candida isolates showed resistance or nonwild-type MICs to fluconazole, itraconazole, posaconazole, and amphotericin B, respectively. Notably, 15.9% of patients and 3.7% of isolates showed mixed Candida infections and multidrug resistance, respectively. The low-level resistance to antifungal agents observed in the present study may be explained by the fact that none of the participants had prior and prolonged exposure to these antifungals. However, more focus should be placed on the mechanisms of reduced susceptibility and low-level resistance in Candida species since they can serve as stepping stones to developing clinical resistance. Alongside this, it seems a must to understand the local epidemiology of Candida spp. and their susceptibility pattern.

Diabetes and Fungal InfectionA Didactic Relationship

Oral fungal infections are frequently encountered in clinical practice, and with the advent of the Coronavirus disease 2019 (COVID19) pandemic, their incidence has quite increased. Increased emergence of oral candidal and non candidal infections is evident in patients with uncontrolled diabetes, patients on steroids or antibiotic therapies, and immunocompromised and immunosuppressed individuals. Also, habits of smoking and alcohol consumption, intake of carbohydrate-rich food, and salivary dysfunction have many times influenced the colonisation of fungal infections in the oral cavity. Aspergillosis once considered exotic is now more prevalent than before and presents itself in two forms: non invasive or invasive form, which has led to the rapid dissemination of the disease. Hence, a timely diagnosis of such lesions is important to prevent their invasion into other parts of the body. This article discusses a rare case report of Aspergillosis occurring in the oral cavity at the site of the extraction socket in a 50-year-old woman, who is a known diabetic without any history of COVID-19 infection. Aspergillosis unlike other fungal infections of the oral cavity has been reported more in immunocompetent individuals. Here, we report a unique case limited to the oral cavity in an immunocompromised patient.

Emphasis on Temporal Association between Oral Verruciform Xanthoma and Candidal Infection: A Case Report

Emphasis on Temporal Association between Oral Verruciform Xanthoma and Candidal Infection: A Case Report

Isolation and Antifungal Susceptibility of Candida spp. from Pediatric Patients in Kurdistan of Iraq

Candida species are considered the most common opportunistic human fungal pathogen due to the presence of various virulence factors, including its ability to form a biofilm that aids in oral candidiasis. Pediatric patients are more susceptible to oral candidiasis than healthy pediatric because of the factors that encourage Candida oral carriage. This current study aims to isolate, evaluated the antifungal effect on Candida spp. and participated in oral candidiasis of pediatric patients in Sulaymaniyah and Kirkuk city. The study was performed from September 2021 to February 2022 on two groups of pediatrics which including pediatric patients (n=160) and healthy pediatric (n=50) as a control group. Oral swabs were obtained from 210 participants in the Kurdistan Region of Iraq at the Pediatric teaching hospital of the Sulaymaneyah and Kirkuk governorates. To culture the swabs, Sabouraud dextrose agar (SDA) medium was used. HiCrome™ Candida Differential agar used to identify Candida isolated, then depending on the internal transcribed spacer (ITS) region using confirmed polymerase chain reaction. Antifungal sensitivity was done for all C. albicans and non-albicans isolates using five common antifungal disks. Among of the 160 sample of pediatric patient 62 (38.8%) positive for Candida spp. which it is including 17 (27.4 %) and 26 (41.9%), 19 (30.6%) breast feeding, bottle feeding and mixing respectively. While within 50 samples of control group 13 (26%) were positive for Candida spp. which including 2 (15.4%), 9(69.2%), 2(15.4%) of same respectively feeding types. Regarding to the antifungal susceptibility the results showed that C. albicans had higher resistance rates against itraconazole, ketoconazole, and clotrimazole than the non-albicans Candida species However, highly resistant rate were detected in Itraconazole and Ketoconazole with 23.7% and 54.4% respectively, for all Candida species. The Current study concluded that oral candidiasis was more predominant in pediatric patients in compare to healthy pediatric also, and C. albicans is the most prevalent etiologic agent. However, higher rate of sensitivity were detected between Candida species for nystatin, which may suggest as the main treatment for oral Candida infections.

Efficacy of endemic Algerian essential oils against single and mixed biofilms of Candida albicans and Candida glabrata

ObjectivesThis study investigated the in vitro effect of Origanum glandulosum, Ammoides verticillata, and Saccocalyx satureioides essential oils against planktonic cells and biofilms formed by single and mixed species of Candida albicans and Candida glabrata oral isolates. The effect of the essential oils in combination with amphotericin B on planktonic cells was also studied. DesignThe antifungal susceptibility of planktonic cells was evaluated by disc diffusion and broth microdilution methods. Resazurin assay and scanning electron microscopy (SEM) were employed to determine the antibiofilm activity. The combinatory effect was evaluated by the checkerboard method. Essential oils were characterized by gas chromatography–mass spectrometry (GC-MS). ResultsThe minimal inhibitory concentrations (MICs) and the minimum fungicidal concentrations (MFCs) of the studied essential oils were ranged between 250 and 2000 µg/mL. Biofilms were inhibited and eradicated by the essential oils at sub-inhibitory concentrations of 500 and 1000 µg/mL, respectively. SEM studies revealed a reduction in the preformed biofilm as a result of Origanum glandulosum essential oil treatment for single and mixed biofilms. Synergistic activity was found when Origanum glandulosum essential oil was combined with amphotericin B against Candida albicans. GC–MS analysis revealed that thymol was the major compound in Origanum glandulosum (38.36 %) and Ammoides verticillata (48.99 %) essential oils, while Saccocalyx satureioides essential oil was dominated by borneol (27.36 %). ConclusionsThe studied essential oils showed significant antifungal and antibiofilm activities, which support their effectiveness as promising candidates for the management of oral Candida infections.

IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis

During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral Candida infection. Here we report that EphA2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 restrains IL-23 secretion from and migration of dendritic cells. IL-23 signaling prevents ferroptotic host cell death during infection to limit inflammation and immunopathology. Further, host cell ferroptosis limits antifungal effector functions via releasing the lipid peroxidation product 4-hydroxynonenal to induce various forms of cell death. Thus, we identify ferroptotic cell death as a critical pathway of Candida-mediated renal immunopathology that opens a new avenue to tackle Candida infection and inflammation.

Candidiasis and Other Bacterial Infections among Patients Diagnosed with Burning Mouth Syndrome.

Background and Objectives: Burning mouth syndrome (BMS) is a state in which a patient experiences intraoral burning or a dysesthetic sensation without clinically evident causative lesions in the oropharyngeal area. The disorder is linked to a variety of conditions, including dry mouth, Candida, and bacterial infections. The aim of this study was to determine the incidence of oral Candida and/or bacterial infections among patients with BMS and whether they have an effect on pain/burning and salivary flow levels. Objectives: (1) Gather patient data regarding the presence of oral infections, dry mouth, and pain levels in the morning, afternoon, and evening periods; (2) data analysis and assessment to determine medians, means, frequencies, correlations, and statistically significant differences between patient groups. Materials and Methods: Overall, 173 patients (23 males and 150 females) with BMS and 13 controls (five males and eight females) took part in the study. We measured pain/burning levels, unstimulated and stimulated salivary flow, the percentage of patients infected with Candida species and/or bacterial species, and the said species growth in Petri dishes. Results: Candida albicans was the most commonly found infection among patients with BMS (n = 28, 16.2%). Overall, 21.4% patients with BMS were diagnosed with either C. albicans or another Candida species. Enterobacter had the richest growth among patients with BMS (7.5% out of the infected 10.4% BMS patients). No statistical significance could be noted between the existence of either Candida species or bacterial species infections and changes in pain/burning and salivary flow levels. Negative correlations were noted between age and unstimulated and stimulated salivary flow, and positive correlations were noted between age and Candida andspecific bacteria species’ growth levels. Conclusions: Although patients with present bacterial or Candida infections showed a marginal increase in pain/burning levels, no direct statistically significant associations could be made between the presence of Candida species or other bacteria and the symptoms among patients with BMS.

A preliminary study of suppression of candida infection by miconazole mucoadhesive tablets in oral or oropharyngeal cancer patients undergoing radiotherapy

Elevated numbers of candida in the oral cavity often lead to oral candidiasis development in patients undergoing radiotherapy for oral or oropharyngeal cancer. This study aimed to verify the effect of miconazole mucoadhesive tablets on suppression of oral candida infection during radiotherapy. For this preliminary interventional study, miconazole mucoadhesive tablets were attached to the oral mucosa for 14 days from when grade 2 oral mucositis appeared in patients with oral or oropharyngeal cancer receiving radiotherapy, and the incidence of oral candidiasis was investigated. Various clinical factors were examined; univariate and multivariate Cox regression analyses were performed to investigate and compare the efficacy of this drug in preventing oral candidiasis with results of our previous study as historical control. Miconazole mucoadhesive tablets were administered to 18 patients, and oral candidiasis was observed in one patient (5.6%) after treatment completion. Among 144 historical control patients, 43 (29.9%) developed oral candidiasis. Multivariate Cox regression showed that miconazole mucoadhesive tablets significantly reduced oral candidiasis development during radiotherapy (p = 0.049, Hazard ratio 0.136, 95% confidence interval 0.019–0.994). This preliminary study suggests the efficacy of miconazole mucoadhesive tablets in preventing oral candidiasis in oral or oropharyngeal cancer patients treated with radiotherapy.Trial registration: Japan Registry of Clinical Trials (jRCT), jRCTs071190023. Registered 3 September, 2019.

Solubilization and purification of phosphatidylserine synthase from Candida albicans

Systemic infections by Candida spp. are associated with high mortality rates, and this is related, in part, to limitations in current antifungals. In this regard, the phosphatidylserine (PS) synthase from Candida albicans, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals. The reasons include: 1) Cho1 is required for oral and systemic Candida infection in the mouse model and is essential for viability in the fungal pathogen Cryptococcus neoformans; 2) this gene and gene product is absent in humans, and 3) it is a highly conserved protein among many human fungal pathogens. Inhibitors of Cho1 could be used as lead compounds for drug development. Small molecule screening is one way to develop specific inhibitors. This requires protein purification of the drug target. Due to the transmembrane nature of Cho1, therefore, we aim to solubilize and purify the native form of the Cho1 protein. Initially, four nonionic detergents (Digitonin, n‐Dodecyl‐b‐D‐ Maltopyranoside [DDM], n‐Tetradecyl‐b‐D‐Maltopyranoside [TDM], and Triton X‐100) were used to solubilize an HA‐tagged Cho1 protein from the total microsomal fraction. Analysis by Blue Native PAGE (BN‐PAGE) and immunoblotting revealed a single band corresponding to Cho1 protein in these four solubilized fractions. A radiochemical enzymatic assay suggests that the digitonin‐ and DDM‐solubilized fractions have more PS synthase activity than the TDM‐ and Triton X‐100‐ solubilized fractions. Using a pulldown assay for the HA‐tagged Cho1 in the digitonin‐solubilized fraction reveals a single band in BN‐PAGE, and a subsequent 2D gel electrophoresis confirms the purity of this protein following silver staining. The comparative mobility by BN‐PAGE gives an apparent MW of Cho1 of ~178 kDa. Based on the amino acid sequence, this would suggest a hexameric form of the CandidaCho1. This is quite different from the structure of other membrane phospholipid synthases, which all appear to be dimers. Preliminary negative staining and TEM single particle analysis suggests the presence of a hexamer population of Cho1 complex in the pulldown sample. The hexametric Cho1 is predicted to be assembled as a trimer of dimers. As expected, a subsequent 2D particle classification on the TEM images has shown different assemblies of Cho1 dimers, mostly trimers of dimers, strengthening the claim that Cho1 forms native trimers of dimers.In order to achieve large‐scale purification for small molecule screening, three protein affinity tags (His8‐, GST‐, & MBP‐tag) were added to the Cho1 protein, and a TEV protease recognition sequence was also added between Cho1 protein and the tags. All three different versions of Cho1 protein showed expression, but His8‐tagged Cho1 stands out among the others because it retains protein activity and is compatible with digitonin. Though nonspecific bands exist in the initial His‐tag affinity purification, a subsequent TEV protease treatment and a second His‐tag affinity purification were able to clear the nonspecific bands and result in a very homogeneous band of Cho1 protein. In sum, we are able to achieve an over‐500‐fold and microgram‐scale purification of Cho1. We plan to further characterize the pure Cho1 protein and use it in future small molecule screening.

IL-23 signaling limits ferroptosis-driven immunopathology during systemic fungal infection

Abstract Pattern recognition receptors initiate antifungal immune responses during infection. Recently, we identified that the ephrin type-A receptor 2 (EphA2) is a fungal β-glucan receptor which orchestrates innate immune responses and prevents oral Candida infection. However, the role of EphA2 during invasive candidiasis (IC) remains unknown. Here we found that EphA2 induces renal inflammation and injury; thus, promoting immunopathology during IC. In Epha2−/− mice, dendritic cells migrated more efficient in infected tissues, while secreting more IL-23. Furthermore, Epha2−/− mice had reduced lipid peroxidation in kidneys, a marker of ferroptotic cell death. Pharmacological inhibtion of ferroptosis increased macrophage fungal killing, reduced inflammation, and increased disease outcomes during IC. Previously, IL-23 signaling has been associated with myeloid cell survival during candidiasis. Treatment of macrophages with IL-23 reduced ferroptotic macrophage cell death and excessive inflammation, while increasing killing capacity. Furthermore, IL-23 treatment of infected mice increased survival and reduced ferroptosis during IC. Collectively, our study demonstrates that ferroptotic host cell death is linked to immunopathology and can be targeted by recombinant cytokine therapy during fungal infection. This work was supported in part by NIH grant R00DE026856, an American Association of Immunologists Careers in Immunology Fellowship, and a TLI Seed grant to MS

Prevalence and risk factors for oral HPV16/18 and candida in Japanese people without oral cancer or premalignant lesions

AbstractAimCurrent studies indicate that oral human papillomavirus (HPV) and candida infection may increase the risk of developing oral cancer. The objective of this study was to investigate the risk factors for HPV16/18 and candida infection in the oral cavity in Japanese people without oral cancer or premalignant lesions.MethodsWe targeted 181 Japanese patients (mean age 59.8 years, range 20–89 years) who visited Hiroshima University Hospital. None of the patients had oral cancer or oral potentially malignant disorder. Oral rinse samples were collected after mouth rinsing. Real‐time polymerase chain reaction (PCR) was performed using type‐specific primers to detect HPV16/18 DNA and Candida albicans/Candida glabrata DNA.ResultsOf the 181 participants, 20 participants (11.0%) were HPV16 DNA positive and three participants (1.7%) were HPV18 DNA positive. Smoker had significant higher positive rates of HPV16 DNA than nonsmoker (P = 0.03). Additionally, binomial logistic regression analysis revealed that smoking was significantly associated with HPV16 DNA (odds ratio 4.11, P = 0.01). Six participants (3.3%) showed co‐infection with HPV16 and C. albicans. No significant association was found between HPV16/18 and C. albicans/C. glabrata. Logistic regression analysis revealed that denture use was significantly associated with C. glabrata (odds ratio 5.09, P = 0.003).ConclusionsTobacco smoke is an important risk factor for oral HPV16 infection. Co‐infection with oral HPV16 and C. albicans can be found in people without oral cancer. Our results highlight the importance of not smoking and regularly cleaning dentures to prevent co‐infection with HPV and candida.

Maternal Medication Transmission through Human Milk

Maternal Medication Transmission through Human Milk

The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis.

Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 μg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of β-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.

English

BACKGROUND As the longevity of human lives has increased, the geriatric population is increasing demonstrating more number of oral candidal infections due to decreased immunity. Natural products are being investigated to be used to treat oral candidiasis in place of synthetic drugs in selective geriatric cases. Propolis is one such natural product, which is time tested and developed by nature as an antimicrobial agent. Its toxicity is very less. It can be used in multiple forms. It has the antioxidant, anti-inflammatory properties apart from antibiotic properties and potency of the material improves as it matures with time. But the constituents of Propolis differ with the different sources of procurement. We wanted to evaluate the efficacy of the Propolis procured from Hubballi against Candida albicans in this study. METHODS In this invitro study, Hubballi Propolis was extracted by maceration and refluxing. Water and 70 % ethanol were used as extraction solvents. Total Phenolic and flavonoid contents were determined by using Folin - Ciocalteu spectrophotometric method and Aluminium chloride colorimetric method respectively. Antimicrobial sensitivity effect of Propolis was estimated by determining the minimum inhibitory concentration (MIC) of the samples. RESULTS The results of the studies revealed that propolis samples have effective antifungal activity against Candida albicans with MIC range from 0.01mg / ml to 0.03 mg / ml and comparable high total phenolic (TP) and total flavonoid (TF) contents ranging from 175.4 ± 5.7 to 192.2 ± 3.3 and 33.08 ± 10 to 31.73 ± 8.5 mg / ml respectively. CONCLUSIONS Hubballi Propolis can be used for treating Candidal infection. Further, water extract Propolis showed better in total phenolic content (TPC) and total flavonoid content (TFC) than the alcohol extract. This finding is important to overcome the disadvantage of alcohol extract and hence very useful for application in Dentistry, cosmetics and pharmaceutical industry. KEY WORDS Antifungal Activity, Hubballi Propolis, Flavonoid Content, Phenolic Content

Biomaterials for the Prevention of Oral Candidiasis Development.

Thousands of microorganisms coexist within the human microbiota. However, certain conditions can predispose the organism to the overgrowth of specific pathogens that further lead to opportunistic infections. One of the most common such imbalances in the normal oral flora is the excessive growth of Candida spp., which produces oral candidiasis. In immunocompromised individuals, this fungal infection can reach the systemic level and become life-threatening. Hence, prompt and efficient treatment must be administered. Traditional antifungal agents, such as polyenes, azoles, and echinocandins, may often result in severe adverse effects, regardless of the administration form. Therefore, novel treatments have to be developed and implemented in clinical practice. In this regard, the present paper focuses on the newest therapeutic options against oral Candida infections, reviewing compounds and biomaterials with inherent antifungal properties, improved materials for dental prostheses and denture adhesives, drug delivery systems, and combined approaches towards developing the optimum treatment.

Comorbidities (excluding lymphoma) in Sjögren's syndrome.

The information about comorbidities (excluding lymphoma) in primary Sjögren's syndrome (pSS) is relatively scarce. Cardiovascular disease, infections, musculoskeletal conditions or malignancy are likely the most relevant comorbid conditions in pSS. Different infections (particularly oral candidal infections) and fibromyalgia are extremely frequent in the daily clinical practice. On the other hand, the incidence of cardiovascular events and cancer in pSS is low, so information about them comes from large epidemiological studies or meta-analysis. For this reason, preclinical vascular disease is investigated by different techniques, demonstrating the presence of early atherosclerosis in pSS patients. Coronary events could be slightly more frequent in pSS than in the general population. The overall risk of malignancy in pSS patients seems to be slightly increased, likely due to excess occurrence of lymphoma. An association between pSS and thyroid cancer might exist, although it should be confirmed by further investigations.

Candida albicans-induced EphA2 signaling promotes kidney injury and sepsis during invasive candidiasis

Abstract Pattern recognition receptors (PRRs) play key roles in fungal recognition and initiation of host immune responses. Recently, we identified that the ephrin type-A receptor 2 (EphA2) is a key β-glucan receptor on oral epithelial cells and neutrophils which orchestrates innate immune responses thereby preventing oral Candida infection. However, the contribution of this PRR in the pathogenesis of invasive candidiasis (IC) remains unknown. Although no differences in renal fungal burden could be observed, EphA2-deficient mice were more resistant to C. albicans infection suggesting that EphA2 deficiency enhances renal host tolerance to lethal fungal challenge. By testing renal cytokines, serum NGAL, a marker of renal injury, and the sepsis marker TREM-1, we found that EphA2 deficiency altered the pro- and anti-inflammatory response, reduced renal injury, and sepsis during IC. Epha2−/− mice decreased neutrophil and monocyte recruitment during IC. However, dendritic cells lacking EphA2 migrated more efficient to infected tissue. Since EphA2 is highly expressed on both, hematopoietic and stromal cells, we generated bone marrow chimeric mice. Both Epha2+/+ mice reconstituted with Epha2−/− BM and Epha2−/− mice reconstituted with Epha2+/+ BM were more resistant to IC compared to Epha2+/+ mice reconstituted with Epha2+/+BM. However, these chimeric mice were more susceptible than Epha2−/− mice reconstituted with Epha2−/− BM suggesting that EphA2 deficiency within cells of both compartments, the hematopoietic and the stromal, is required for full protection against IC. Collectively, our data highlight a detrimental role of EphA2 in promoting kidney injury and sepsis during lethal fungal infection.

Association between Antimicrobial Peptide Histatin 5 Levels and Prevalence of Candida in Saliva of Patients with Down Syndrome.

There are no studies on Candida colonization and micropeptides of saliva in any patient. Therefore, we studied the effects of the salivary antimicrobial peptide histatin 5 on oral fungal colonization; subjects were subdivided into Down syndrome (D) and normal (N) groups by age: N-1 and D-1, age <20 years; N-2 and D-2, age >40 years. Histatin 5 concentration in saliva was measured by enzyme-linked immunosorbent assay. Oral Candida species were identified using CHROMagar Candida. Candida colonization was significantly enhanced in the D-1 and D-2 groups compared to the N-1 and N-2 groups. There was no predominant difference in salivary histatin 5 concentration between the D-1 and N-1 groups, but it was significantly lower in the D-2 group than in the N-2 group. Only in the N-2 group was there a correlation between the concentration of histatin 5 and total protein, while no correlation was found in the other groups. In elderly patients with Down syndrome, the decrease in histatin 5 shown in this study may lead to oral Candida colony formation. Therefore, the results of this study suggest that a deficiency of the antimicrobial peptide histatin 5 could possibly induce oral Candida infection in DS.

Antimicrobial photodynamic therapy for oral Candida infection in adult AIDS patients: A pilot clinical trial

BackgroundAntimicrobial photodynamic therapy (aPDT) using methylene blue (MB) plus potassium iodide (KI) has been shown to be effective in killing Candida albicans in many in vitro and in vivo studies, however, there are limited reports of clinical investigations. This study aimed to explore the clinical application of aPDT with MB plus KI for the treatment of oral infection caused by C. albicans in adult acquired immune deficiency syndrome (AIDS) patients. MethodsA total of 21 adult AIDS patients with C. albicans oral candidiasis were divided into two groups according to MB concentration and received two consecutive aPDT treatments. Immediately before and after the aPDT treatments, C. albicans yeast isolates were recovered to measure the colony-forming units per mL (CFU/mL), biofilm formation, and to analyze the 25S rDNA genotype. Patients were assessed for the clinical recovery of oral lesions and improvement of symptoms. ResultsThe Log10 CFU/mL of C. albicans decreased significantly after the second aPDT but not the first aPDT. There was no significant difference between the two MB concentrations. Both aPDT protocols decreased the oral lesions and clinical symptoms with no significant difference after 2-fraction aPDT. The biofilm formation of C. albicans isolates did not change before and after aPDT. The killing efficiency of 2-fraction-aPDT was not associated with either biofilm formation or 25S rDNA genotype. ConclusionsTwo-fraction-aPDT with MB plus KI could reduce the number of viable C. albicans fungal cells and improve the clinical symptoms of oral candidiasis in adult AIDS patients, regardless of the biofilm formation or 25S rDNA genotype of infected C. albicans isolates.