Punica granatum as Anticandidal and Anti-HIV Agent: An HIV Oral Cavity Potential Drug.

The oral cavity is crucial from diagnosis to adherence to HAART therapy in the HIV/AIDS population; consequently, drugs that can maintain healthy conditions in the oral cavity are necessary for patients with HIV/AIDS. Punica granatum (pomegranate) is a tree that has been employed extensively for centuries in the traditional medicine of ancient cultures for the treatment of a wide range of diseases, including oral and dental diseases. In recent decades, its potent anticandidal properties have been shown, especially on Candida albicans, the cause of the most common clinical manifestation in HIV patients. The present work contributes to the review of the anti-HIV and anticandidal properties of the plant species P. granatum as involved with the oral cavity. The literature reviewed revealed that crude extracts of pomegranate and its main isolated compounds possess inhibitory activity on different HIV targets, including binding viral proteins and the three replicative HIV enzymes. In addition, in the literature reviewed, pomegranate exhibited anticandidal effects on 10 different species. Thus, pomegranate appears to be an excellent candidate to explore and incorporate into the treatment of the oral cavity of HIV/AIDS patients, in that, in addition to its pharmacological effects such as antiviral and anticandidal, pomegranate represents an easily available, inexpensive, and safe natural source.

Anti-HIV and Anti-Candidal Effects of Methanolic Extract from Heteropterys brachiata.

Nowadays, the HIV pandemic is far from controlled. HIV+/AIDS patients show a serious risk of developing resistance to HIV antiretroviral drugs and to be orally colonized by albicans and non-albicans Candida strains resistant to antifungals. As a consequence, new drugs that possess anti-candidal and anti-HIV effects would represent an alternative in the comprehensive treatment of HIV+/AIDS patients. The present study evaluates the possible anti-HIV and anti-Candida effects of a methanolic extract from Heteropterys brachiata (Hb MeOH), an American tropical plant. The anti-HIV effect of Hb MeOH was tested using a non-radioactive colorimetric method (Lenti RT® Activity Assay; Cavidi Tech) that uses reverse transcriptase of HIV-1 enzyme as enzymatic target. The anti-candidal effect of HbMeOH extract was evaluated by following a standardized test protocol of microdilution for yeast using the Candida albicans strain ATCC® 90028. The Hb MeOH at 1 mg/mL concentration shows 38.5% RT-HIV inhibition, while Hb MeOH at 10 mg/mL concentration produced 98% C. albicans growth inhibition. Our findings show that the Hb MeOH possesses a strong anti-candidal activity and moderate anti-HIV effect and suggests that the plant extract could be considered as a potential candidate for HIV/AIDS treatment.

Impacto de enfermedades orales asociadas a estrés sobre la calidad de vida / Impact on Quality of Life of Oral Diseases Related to Stress

Resumen: Se ha sugerido que enfermedades de la mucosa oral asociadas a estrés impactan negativamente la calidad de vida. Sin embargo, la información no es concluyente. El objetivo fue comparar la calidad de vida asociada a salud bucal en dos grupos: Casos (21 pacientes de una clínica de enseñanza de medicina bucal con diagnóstico de liquen plano oral, estomatitis aftosa recurrente y síndrome de boca dolorosa; Control (42 sujetos sanos) pareados por edad y género. Se aplicó el cuestionario perfil de impacto de salud oral. Resultados: El análisis estadístico mostró que el grupo casos tiene peor calidad de vida (p 0.03) comparado con el de los controles, específicamente en las dimensiones incomodidad psicológica (p 0.027); inhabilidad física (p 0.004); e incapacidad (p 0.002; RM 5.63 IC 1.58-20.80). Se concluye que los sujetos que padecen enfermedades de la mucosa oral relacionada a estrés tienen mala calidad de vida.

Abstract: It has been suggested that oral mucosa diseases related to stress have a negative impact on the quality of life. However, the information regarding which aspects are the most affected is inconclusive. The objective was to compare the quality of life associated with oral health in two groups: Cases formed by 21 patients coming from a teaching clinic, suffering oral lichen planus, recurrent aphthous stomatitis, and burning mouth syndrome; Control formed by 42 healthy subjects matched for age and gender. Oral Health Impact Profile questionnaire was applied. Statistical analysis showed that group Cases has worse quality of life (p 0.03) than the one of controls, specifically on psychological discomfort (p 0.027), physical disability (p 0.004); and handicap dimensions (p 0.002; RM 5.63 IC1.58-20.80). It was concluded that patients suffering oral mucosa disease related to stress showed poor quality of life.

[Factors related to oral candidiasis in HIV children and adolescents, species characterization and antifungal susceptibility]. / Factores relacionados a candidiasis oral en niños y adolescentes con VIH, caracterización de especies y susceptibilidad antifúngica.

BACKGROUND: Factors associated with candidiasis and colonization in HIV-positive children and adolescents in developing countries are not well understood. AIM: To identify the factors associated with oral Candida colonization and candidiasis in institutionalized HIV-positive children and adolescents in Tijuana, México, as well as the response of the isolates to antifungals. MATERIALS AND METHODS: Sample of the oral mucosa of 30 HIV positive children and adolescents were obtained to isolate and identify Candida species by culture and metabolic profile. Antifungal drugs susceptibility was determined according to CLSI. Indicators of immunological and virologic failure were classified in accordance to WHO criteria. RESULTS: Six Candida species were identified from oral mucosa, 53% colonizers and 47% in candidiasis. Factors associated with candidiasis and oral colonization were viral load (p = 0,001), CD4+ counts (p = 0,002) and HAART regimen (p ≤ 0,014). The most prevalent species was C. glabrata (33%), but C. albicans (27%) was more resistant to fluconazole (p = 0,001). Itraconazol resistant species were identified in regimens that include an NNRTI (p = 0,041). CONCLUSION: HIV-positive children and adolescents living in an orphanage showed high prevalence of colonizing Candida spp. and resistance to antifungals, related to NNRTI.

Factores relacionados a candidiasis oral en niños y adolescentes con VIH, caracterización de especies y susceptibilidad antifúngica / Factors related to oral candidiasis in HIV children and adolescents, species characterization and antifungal susceptibility

Resumen Introducción: Se desconocen los factores asociados a la candidiasis oral en población pediátrica con infección por VIH de los países en desarrollo. Objetivo: Identificar los factores asociados a la colonización por Candida, candidiasis oral y la susceptibilidad in vitro a antifúngicos, en niños y adolescentes con infección por VIH institucionalizados en la ciudad de Tijuana, México. Materiales y Métodos: Se examinó la cavidad oral de 30 niños y adolescentes con infección por VIH, se obtuvo una muestra de la mucosa oral para identificar las especies de Candida mediante cultivo y auxonograma. La susceptibilidad a los antifúngicos se determinó de acuerdo al CLSI. Los indicadores del estado inmunológico y falla virológica se clasificaron conforme a la OMS. Resultados: Se identificaron seis especies de Candida, 53% colonizantes y 47% causantes de candidiasis. Los factores asociados a candidiasis fueron alta carga viral (p = 0,001), menor recuento de LTCD4+ (p = 0,002) y esquema TARAA (p ≤ 0,014). La especie prevalente fue C. glabrata (33%); sin embargo, C. albicans (27%) fue más resistente a fluconazol (p = 0,001). Las especies resistentes a itraconazol se identificaron en esquemas que incluyen un INNTR (p = 0,041). Conclusiones: Los niños y adolescentes con infección por VIH institucionalizados mostraron una prevalencia elevada de Candida spp. colonizante y resistencia a los antifúngicos relacionada con los INNTR .

Background: Factors associated with candidiasis and colonization in HIV-positive children and adolescents in developing countries are not well understood. Aim: To identify the factors associated with oral Candida colonization and candidiasis in institutionalized HIV-positive children and adolescents in Tijuana, México, as well as the response of the isolates to antifungals. Materials and Methods: Sample of the oral mucosa of 30 HIV positive children and adolescents were obtained to isolate and identify Candida species by culture and metabolic profile. Antifungal drugs susceptibility was determined according to CLSI. Indicators of immunological and virologic failure were classified in accordance to WHO criteria. Results: Six Candida species were identified from oral mucosa, 53% colonizers and 47% in candidiasis. Factors associated with candidiasis and oral colonization were viral load (p = 0,001), CD4+ counts (p = 0,002) and HAART regimen (p ≤ 0,014). The most prevalent species was C. glabrata (33%), but C. albicans (27%) was more resistant to fluconazole (p = 0,001). Itraconazol resistant species were identified in regimens that include an NNRTI (p = 0,041). Conclusion: HIV-positive children and adolescents living in an orphanage showed high prevalence of colonizing Candida spp. and resistance to antifungals, related to NNRTI.

p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: A study of 208 cases.

BACKGROUND: The use of p16 and p53 as biomarkers of malignant transformation of oral epithelial dysplasia (OED) and biological behavior of oral squamous cell carcinoma (OSCC) is controversial. AIM: To determine the immunoexpression of p16 and p53 in OED and OSCC and to establish their possible relation to histopathological grading of OED/OSCC. MATERIALS AND METHODS: Ninety-six OEDs (40 mild, 36 moderate, and 20 severe dysplasia); and 112 OSCCs (64 well-differentiated, 38 moderately differentiated, and 10 poorly differentiated) coming from archives of four centers of oral pathology were included. Histological slides from all cases were processed with immunohistochemical technique using anti-p53 and anti-p16 antibodies. The intensity of the immunoreactivity were classified using the ImageLab®MCM systemas follows: <60 mild, >60-<90 moderate, and >90 strong. Forstatistical purposesa χ2 test (P < 0.05) was performed. RESULTS: Severe dysplasia show highest relative frequency of p16-positive (35.5%), whereas p53 is associated with mild dysplasia (P = 0.04). Moderately differentiated OSCC had larger relative frequency of p16-positive and p53-positive cases (47.3% both circumstances) (P > 0.05). Statistical association of p16-positive and p53-positive cells to basal stratum of OED (P = 0.0008; P = 0.0000, respectively) and p16-positive cells and p53-positive cells to perivascular zone of OSCC (P = 0.001; P = 0.0000, respectively) was found. CONCLUSIONS: p16 and p53 could be not specific enough to identify patients suffering OED with high risk to malignancy; however, the evaluation of the presence of p16 and p53 in the tumoral invasive front of OSCC could contribute to establish the tumor progression.

Oral manifestations after immune reconstitution in HIV patients on HAART.

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P = 0.78), sex (P = 0.41) or previous history of ART (P = 0.55) between IR and non-IR patients. In the IR group, the most common OM was parotid enlargement (57.14%) (P = 0.019), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence.

OBJECTIVE: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). METHODS: From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes >500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. RESULTS: A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p = 0.008), and were seen to be dependent upon late appearance of the mycotic lesions (after 24 months under HAART). CONCLUSIONS: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Prevalencia de lesiones orales en pacientes pediátricos mexicanos con infección por el virus de la inmunodeficiencia humana / HIV associated oral lesions in a group of Mexican children

Introducción. La infección del virus de la inmunodeficiencia humana (VIH) está caracterizada por una disminución progresiva de los CD4 hasta su total depleción. A las manifestaciones orales se les ha atribuido un importante valor diagnóstico y pronóstico para la enfermedad; sin embargo, la prevalencia de lesiones orales asociadas con el síndrome de inmunodeficiencia adquirida (LOAS) en pacientes pediátricos no está bien establecida. El objetivo del presente trabajo de investigación fue determinar la prevalencia de LOAS y su correlación clínica, inmunológica y viral en pacientes pediátricos VIH/SIDA. Material y métodos. Para este propósito fueron revisados 42 pacientes pediátricos (26 del sexo femenino y 16 del masculino) de la Clínica de Inmunodeficiencia del Hospital Infantil de México Federico Gómez. Resultados. La prevalencia encontrada de lesiones orales asociadas a SIDA fue de 38.1 por ciento, de éstas, la que se presentó con mayor frecuencia fue la candidiosis en la cual se incluyó de acuerdo a su presentación clínica en: candidiosis eritematosa (19 por ciento), candidiosis pseudomembranosa (11.9 por ciento) y queilitis angular (7.1 por ciento); el crecimiento parotídeo 4.7 por ciento, la xerostomía se observó en 7.1 por ciento, gingivitis y periodontitis asociada a VIH 4.7 por ciento, herpes labial en 2.4 por ciento y depapilación lingual 2.4 por ciento. Conclusiones. No se observó relación entre las lesiones bucales con la cantidad de CD4 ni tampoco con la carga viral; sin embargo, sí se encontró relación entre la clasificación clínica y la prevalencia de lesiones bucales. Se debe estudiar más ampliamente la utilidad de LAOS como marcadores pronósticos del SIDA en pacientes pediátricos.