Alan Grupioni Lourenço

Unusual Orofacial Manifestations of Histoplasmosis in Renal Transplanted Patient

Histoplasmosis is a fungal infection caused by the Histoplasma capsulatum. Mucosal manifestations are uncommon, but, when present, they are usually associated with pulmonary or chronic disseminated infection. The course of the disease is often related to the host immune response. The purpose of this article is to describe the clinical and microscopic findings of unusual involvement of nasal cartilage and septal destruction, and oral lesions of histoplasmosis in an immunosuppressed patient who presented an unusual form of the disease.

Semen lactoferrin promotes CCL20 production by epithelial cells: Involvement in HIV transmission.

AIM To study the effect of seminal plasma on Chemokine (C-C motif) ligand 20 (CCL20) production by epithelial cells and its relationship with lactoferrin. METHODS HEC-1A cells, a cell line derived from a monostratified endocervical epithelium, were incubated with samples of seminal plasma (diluted 1:10 in culture medium) recovered from human immunodeficiency virus (HIV) seronegative (HIV-) or HIV seropositive (HIV+) subjects. Recombinant human interleukin 1 beta (IL-1β) was used as positive control, and culture medium only as negative control. The measurement of CCL20 production in the supernatants of HEC-1A cells and of lactoferrin in seminal plasma was determined by enzyme-linked immunosorbent assay techniques. A fractionation of seminal plasma proteins was performed by ion exchange chromatography on a pool of seminal plasma specimens from HIV- subjects. Each fraction was tested for its ability to stimulate the production of CCL20 by HEC-1A cells and for its lactoferrin concentration. The HIV viral load in seminal plasma samples from HIV+ patients was measured using the HIV-Monitor kit (Roche Diagnostic Systems, Branchburg, NJ, United States). RESULTS The positive control IL-1β was responsible for an increase of 11.36 ± 3.36 times in the production of CCL20. Stimulation of HEC-1A cells was performed in 34 seminal plasma samples (22 from HIV+ subjects and 12 from HIV- subjects). The mean production of CCL20 by HEC-1A in presence of seminal plasma from HIV- and HIV+ subjects was respectively 5.38 ± 0.91 and 7.57 ± 3.26 times higher than that obtained with the untreated cells (P < 0.05 between the two groups). Using the same 34 specimens of seminal plasma, no correlation was observed between the concentration of total proteins in seminal plasma and their ability to stimulate the secretion of CCL20 by HEC-1 cells. In contrast, the ability to produce CCL20 by HEC-1A cells correlated to the concentration of lactoferrin in the seminal plasma samples (r coefficient = 0.56; CI: 0.26-0.76; P < 0.001). After fractionation by ion exchange chromatography, the seminal plasma fractions exhibiting the highest concentrations of lactoferrin were responsible for the greatest stimulation of CCL20 production by HEC-1A cells (r coefficient = 0.89; CI: 0.78-0.95; P < 0.0001). CONCLUSION Lactoferrin present in seminal plasma correlated with an increased production of CCL20 by HEC-1A cells and therefore could facilitate HIV entry through the genital mucosa.

Potential contribution of saliva to the sexual transmission of HIV through the secretion of CCL20 by genital epithelial cells

Saliva can be considered as an important actor during sexual intercourse. However, there is no data concerning its influence on HIV sexual transmission. The aim of this study was to evaluate the role of whole saliva on the in vitro secretion of CCL20 by monolayered HEC‐1A endocervical epithelium cells. HEC‐1A cells were cultivated in 96‐well microplates and incubated with specimens of whole saliva collected from 57 subjects tested seropositive (n = 34) or seronegative (n = 23) for HIV and presenting different oral conditions (healthy periodontally, n = 22, and gingivitis/periodontitis, n = 35). The production of CCL20 in the supernatants of HEC‐1A cells after overnight incubation at 37°C was quantified using ELISA. The salivary concentration of lactoferrin (Lf) and IL‐1β was tested by ELISA. Saliva samples were found able to stimulate dramatically the production of CCL20 by epithelial cells, increasing this synthesis by a mean factor of 38.1 with reference to untreated cells. This stimulation was equivalent to that observed with IL‐1β used as positive control. Although no difference was observed according to oral condition, HIV status or salivary concentration of Lf and IL‐1β, the high salivary concentration of the latter protein could acknowledge in large part for the overproduction of CCL20 by HEC‐1A cells when stimulated by saliva. Saliva was shown to significantly increase CCL20 secretion and may be responsible for an enhanced recruitment of dendritic/Langerhans cells at the genital level. These results suggest that saliva could facilitate HIV entry and possibly other pathogens through the genital mucosa during heterosexual intercourse. J. Med. Virol. 86:58–63, 2014.

Lactoferrin, A Marker for Periodontal Disease

This study evaluated the salivary concentrations of lactoferrin (Lf) in HIV-seropositive and -seronegative subjects correlating these levels with the incidence of periodontal disease, quantity of Candida spp and systemic condition of the HIV-seropositives (viral load and T lymphocytes CD-4+ count and antiretroviral therapy). Whole saliva samples were obtained from 109 subjects who were divided into four groups according to the extent of their HIV infection and their periodontal condition. The salivary Lf concentrations were determined by a standard enzyme-linked immunosorbent assay and the quantification of Candida spp. was obtained from all subjects. Among the HIV- participants, higher concentrations of Lf were found in individuals with periodontal diseases (p<0.0001). A similar result was found for HIV+ participants (p<0.0001). No correlation was found between the concentration of salivary Lf and the quantification of Candida spp or between the Lf concentration and the systemic condition of the HIV+ subjects. The existence of periodontal diseases can modulate an early inflammatory process in the oral mucosa by increasing the expression of Lf, where Lf can act as an antibacterial peptide in HIV- and HIV+ patients. These results suggest that Lf is a possible marker for periodontal diseases in immunocompetent and immunocompromised subjects.

Oral health management of 97 patients living with HIV/AIDS in Ribeirão Preto, São Paulo, Brazil.

Considering the changes antiretroviral therapy (ART) has brought to the treatment of HIV infection, the current clinical and laboratory profiles of HIV/AIDS individuals referred to oral health centers are crucially important in instructing dentists about the oral health management of these patients. The aim of the present study was to determine the clinical and laboratory profiles of HIV-infected individuals referred to a clinic for patients with special needs between 2005 and 2012 by retrospectively analyzing their dental records. A total of 97 records of HIV patients referred to the School of Dentistry of Ribeirão Preto, Universidade de São Paulo - USP, were analyzed. The Mann-Whitney test was used to determine the associations between mean CD4+ counts, mean viral load, and the presence of HIV-related oral lesions (HIV-OL). Most of the patients were male, and their mean age was 38.3 years. Eighty-nine (92%) patients were on regular ART, 77 (79.4%) had a CD4+ count higher than 200 cells/mm3, and 63 (64.9%) had an undetectable viral load. Twenty patients (20.6%) presented with some HIV-OL, including pseudomembranous and/or erythematous candidiasis and angular cheilitis, which were correlated with a low CD4+ count and with an undetectable viral load (p < 0.05). Among the branches of dentistry, periodontics, followed by surgery and restorative dentistry, was the most sought-after specialty, and no intercurrent events were observed during the dental treatment. It may be concluded that there are no restrictions on the dental treatment of patients on regular ART, It is important, though, that the treatment be based on local characteristics and on the prevention of oral diseases.

Influence of Antiretroviral Therapy and Periodontal Disease on Human Salivary Beta-Defensin 2 in Patients Infected with HIV

Studies have addressed periodontal disease biomarkers in salivary proteins associated with innate immunity, mostly due to the alteration in the concentration of many of these proteins in the presence of inflammation. On the other hand, some systemic diseases can modify salivary protein concentrations, which may change their importance or role as specific biomarkers. To study the relationship between periodontal disease and concentrations of human beta-defensin 2 (HBD-2) in the saliva of patients infected and not infected with HIV. To evaluate the association between HBD-2 salivary concentration and viral load, the TCD4+ lymphocyte count (LTCD-4+) and the use of antiretroviral therapy (ART) was assessed in HIV infected patients. Concentrations of HBD-2 were measured in 48 patients not infected with HIV and 53 HIV-infected patients by ELISA, and these data were compared according to periodontal status. Within the group of HIV-infected patients, measures of HBD-2 were assessed according to viral load, LTCD-4+ count and the use of ART. Concentrations of salivary HBD-2 were associated with periodontal disease in non-HIV-infected patients. In HIV-infected patients, salivary HBD-2 was associated with serum status and the use of ART, but it was not related to the periodontal condition. The presence of HBD-2 in the saliva of HIV-infected patients showed no correlations with LTCD-4+ count or viral load. HBD-2 could be a periodontal biomarker in non-HIV-infected patients, but in HIV-infected patients, while salivary HBD- 2 was influenced by the serum status and ART use, it was not correlated with the periodontal condition.

Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis

ABSTRACT Introduction: Current studies show that, even in the era of antiretroviral therapies, HIV-1 infection is associated with more severe and frequent refractory chronic periodontitis. Areas covered: This review, based on a systematic analysis of the literature, intends to provide an update on factors that may be involved in the pathogenesis of periodontal disease in HIV-1-infected patients, including local immunosuppression, oral microbial factors, systemic inflammation, salivary markers, and the role of gingival tissue as a possible reservoir of HIV-1. Expert commentary: The therapeutic revolution of ART made HIV-1 infection a chronic controllable disease, reduced HIV-1 mortality rate, restored at least partially the immune response and dramatically increased life expectancy of HIV-1-infected patients. Despite all these positive aspects, chronic periodontitis assumes an important role in the HIV-1 infection status for activating systemic inflammation favoring viral replication and influencing HIV-1 status, and also acting as a possible reservoir of HIV-1. All these issues still need to be clarified and validated, but have important clinical implications that certainly will benefit the diagnosis and management of chronic periodontitis in HIV-1-infected patients, and also contributes to HIV-1 eradication.