Oral Infections and Systemic Health - More than Just Links to Cardiovascular Diseases.

PURPOSE: During the past 20 years, a plethora of research reports has been published showing a statistical association between poor oral health and cardiovascular diseases. The aim of this narrative review was to focus on associations between oral infections and non-atherosclerosis-related systemic diseases. MATERIALS AND METHODS: An open literature search and evaluation of articles were conducted on Medline and Cochrane databases with the key words 'oral infection', 'periodontitis', 'pneumonia', 'osteoarthritis', 'rheumatic diseases', 'inflammatory bowel disease', 'kidney disease', 'liver diseases', 'metabolic syndrome', 'diabetes', 'cancer', 'Alzheimer's disease'. Cardiovascular diseases were excluded from the analysis. RESULTS: The scarcity of controlled studies did not allow conducting a systematic review with meta-analysis on the topics, but dental infections have been shown be associated with several general diseases also beyond the atherosclerosis paradigm. However, there is no causal evidence of the role of dental infections in this regard. Poor oral health has nevertheless often been observed to be associated with worsening of the diseases and may also affect treatments. CONCLUSIONS: Maintaining good oral health is imperative regarding many diseases, and its importance in the daily life of any patient group cannot be over emphasised.

Difference in the expression of inflammatory mediators in gingival crevicular fluid in postmenopausal patients with chronic periodontitis with and without menopausal hormone therapy.

OBJECTIVE: Hormonal changes experience by women produce significant changes in the periodontium. The aim of this study is to assess whether menopausal hormone therapy, in patients diagnosed with moderate chronic periodontitis and menopause presents a beneficial effect, in terms of clinical and immunological outcomes. STUDY DESIGN: Thirty subjects with moderate chronic periodontitis and menopause were selected and assigned to two groups in accordance to the presence of menopausal hormone therapy. Periodontal clinical parameters, microbiological samples and immunological variables were assessed in both groups. Inter-group differences were evaluated using non-paired Student t-tests and chi square tests. Also, Pearson coefficient correlation was performed to determine the correlation between variables. RESULTS: There were statistically significant differences between groups for clinical attachment level, probing pocket depth, interleukin 1ß and interleukin 6. Smoking habit, deeper PPD and higher Il-6 levels in non-menopausal hormone therapy users group, tend to increase the interleukin 1ß GCF levels. These findings were supported by serum estrogen levels. The variables levels were higher in the menopausal hormone therapy users group. CONCLUSION: Within the limitations of the present study, the hypothesis that menopausal hormone therapy user's women will show better periodontal status and differences in immunological variables respect to those being non-menopausal hormone therapy users was supported.

[Diabetes and periodontitis: A bidirectional relationship]. / Diabetes y periodontitis: una relación bidireccional.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, a defect in insulin action or a combination of both. Periodontitis is now considered a chronic localized infection of the oral cavity that can trigger inflammatory host immune responses at local and systemic levels, and can also be a source of bacteremia. It is now known that periodontitis has an influence on the pathogenesis of certain systemic diseases. The biological relationship between diabetes and periodontal disease is well documented. In the mid-90s sufficient scientific support for the association between diabetes and periodontitis was published, and periodontitis was designated as the sixth complication of diabetes. There have been studies that show an improvement in both clinical and immunological parameters of periodontitis and glycemic control in long-term diabetes after treatment of periodontal disease. In addition, scientific evidence confirms that poorer glycemic control contributes to a worse periodontal condition. The interplay between the 2 conditions highlights the importance of the need for a good communication between the internist and dentist about diabetic patients, considering always the possibility that the 2 diseases may be occurring simultaneously in order to ensure an early diagnosis of both.

[Side effects of drugs on the oral cavity]. / Reacciones adversas a medicamentos en la cavidad oral.

Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis.

[Tranexamic acid gel in patients treated with oral anticoagulants]. / Aplicación de un gel de ácido tranexámico en pacientes tratados con anticoagulantes orales.

BACKGROUND AND OBJECTIVE: Patients treated with oral anticoagulants have increased susceptibility to bleeding, and therefore any surgical medical procedure and especially oral surgery requires a therapeutic approach that minimizes bleeding effects in these patients. MATERIAL AND METHOD: The working hypothesis was based on studies of local application of tranexamic acid after maxillofacial interventions as effective therapeutic alternative for the prevention and control of bleeding. The aim was to assess the effectiveness of the application of a gel solution tranexamic acid after tooth extraction in anticoagulated patients in terms of healing time and degree of healing. RESULTS: The results indicate that application of tranexamic acid gel is very effective for consistency and maintenance in the place of action and shows its efficacy as a procoagulant material. CONCLUSIONS: The application of a gel solution of tranexamic acid in oral anticoagulants patients ameliorates healing time and the bleeding time within the first 48-72 h.

Evaluation of p53, caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (Spain).

OBJECTIVE: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior. STUDY DESIGN: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67 RESULTS: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples, there was a significant inverse relationship between the expressions of p53 and caspase-3 and a significant direct relationship between the expressions of p53 and Bcl-2. CONCLUSIONS: Alterations in these proteins appear to operate in combination with premalignant epithelia to create hyperproliferative cell states that favor the acquisition of summative oncogenic errors that confer invasive capacity.

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans.

Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD- samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD- samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions.

New perspectives on the dynamic behaviour of oral lichen planus.

Lichen planus, a chronic inflammatory disease that affects the skin and mucous membranes, is one of the most frequent dermatological disorders of the oral cavity. The prevalence of oral lichen planus ranges from 0.2% to 4%. The triggering factors remain unknown. Oral lichen planus can be considered to be a chronic disease of long duration with a dynamic evolution and frequent changes in clinical appearance. Three successive active stages can be distinguished, without sharp limits between them: an initial stage; a protracted intermediate stage with alternate periods of variable activity and quiescence, which carries a progressively increasing risk of malignant transformation; and a late stage that often ends in a clinically little-known, inactive cicatricial post-lichen stage, which does not respond to steroid treatment but retains the same risk.

Gingival changes during pregnancy: III. Impact of clinical, microbiological, immunological and socio-demographic factors on gingival inflammation.

AIMS: To identify predictor variables involved in exacerbated gingival inflammation associated with pregnancy. MATERIAL AND METHODS: In this cohort study, 48 pregnant and 28 non-pregnant women without periodontitis were included. The pregnant women were evaluated in the first, second and third trimester and at 3 months postpartum, whilst the non-pregnant women were evaluated twice, with a 6-month interval. At each visit, clinical [plaque index (PlI) and gingival index (GI)], hormonal (salivary progesterone and estradiol), immunological [gingival crevicular fluid interleukin-1ß, interleukin-6, tumour necrosis factor-α (TNF-α) and prostaglandin-E(2) ] and microbiological (periodontal pathogens culture) evaluations were performed. Statistical analysis was undertaken using exhaustive chi-square automatic interaction detection (exhaustive CHAID) to analyse the predictive value of the independent outcomes to develop pregnancy GI. RESULTS: PlI was the strongest predictor implicated in the GI throughout pregnancy and after delivery. During the second and third trimesters the presence of Porphyromonas gingivalis significantly contributed to the worsening of gingival inflammation. When compared with the non-pregnant group, significant differences were found in TNF-α amounts and concentrations and in the third trimester site-specific GI. CONCLUSIONS: Bacterial challenge to the gingival tissues, both quantitatively (PlI) and qualitatively (harbouring P. gingivalis) appears to affect the level of gingival inflammation observed during pregnancy.

[Clinical manifestations of hematological non-neoplastic diseases in Dentistry]. / Manifestaciones clínicas de las hemopatías no neoplásicas en Odontología.

Systemic disease can cause clinical manifestations in the oral and maxillofacial area, which is important to recognize because it could be the first symptom of an undiagnosed illness. There are different oral signs that could suggest the clinician a blood disorder, such as pallor, petechiae, ecchymosis, ulcerations, gingival hypertrophy or spontaneous gingival bleeding. In addition, blood disorders will determine the dental management of these patients and the protocol for limiting possible complications that may arise due to the treatment itself. This paper reviews the oral manifestations and dental management of non-neoplastic alterations of red cells, white cells and hemostasis, with emphasis on two-way relationship that must exist between the dentist and the patient's hematologist for making a treatment plan.

Case report of necrotizing sialometaplasia.

INTRODUCTION: Necrotizing sialometaplasia is a rare inflammatory necrotizing reactive process that can involve minor and major salivary glands. Gland tissue ischaemia has been proposed as the aetiology. CASE REPORT: A 21-year-old woman was referred with a 1-week history of bilateral painful swelling of the palate, with the development of two deep ulcers after the first 3 days. Ulcer edges were elevated but not indurated, and the bases had a necrotic appearance. An incisional biopsy of the margin of one ulcer confirmed the diagnosis of necrotizing sialometaplasia. The ulcers spontaneously healed within 8 weeks without treatment. DISCUSSION: The clinical and histological similarity between this entity and a malignant lesion implies a risk of unnecessary or inadequate treatment. This case illustrates the need for an incisional biopsy to be analyzed by an experienced pathologist to establish a correct diagnosis.

Epidemiological study of oral cancer patients in Alava province, Spain.

The authors conducted a retrospective study of oral squamous cell carcinoma (OSSC) patients in the province of Alava, Spain, to investigate the various epidemiological factors involved. The study included data on 30 patients referred to the Otolaryngology Department of our hospital. The authors identified epidemiological data, including age, symptoms, localization, tumor size, risk factors, tumor stage, treatment and outcome. An elevated percentage of risk factors was found, underlining the importance of early diagnosis. The highest prevalence was in the sixth decade of life. The most frequent symptom was pain, and the localization was in the tongue in 70% of cases. Tumor size ranged from 2 to 3 cm, and 85% of patients underwent surgical resection. Risk factors of smoking and drinking affected 50% of the patients.

Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm.

AIM: To determine whether the exacerbated gingival inflammation that develops in pregnant women is related to a change in the subgingival biofilm induced by the increase in hormone levels during pregnancy. MATERIAL AND METHODS: This open cohort study included 48 pregnant and 28 non-pregnant women without periodontitis. Pregnant women were evaluated in the first, second and third trimester and at 3 months after delivery. Non-pregnant women were evaluated twice, with a 6-month interval, assessing microbiological, clinical and hormonal variables at each visit. Total anaerobic counts and frequency of detection and proportions were calculated. The Friedman test with the Bonferroni correction was used for intra-group comparisons and Mann-Whitney U-tests for inter-group assessment. Correlations were analysed by means of Spearman's rank correlation coefficient. RESULTS: Proportions of the subgingival periodontal pathogens did not differ throughout pregnancy, although significant differences were found for all the pathogens after delivery. Porphyromonas gingivalis-positive patients presented an increase in gingival inflammation (p<0.001) that was not related to plaque. Correlations were found between maternal hormone levels and P. gingivalis and Prevotella intermedia. CONCLUSION: Qualitative differences in periodontal pathogens were found from pregnancy to post-partum. Patients harbouring P. gingivalis presented and increased gingival inflammatory status.

Gingival changes during pregnancy: I. Influence of hormonal variations on clinical and immunological parameters.

AIM: To test whether exacerbated gingival inflammation in pregnancy is associated with increased salivary hormone levels and changes in gingival crevicular fluid (GCF) interleukin-1beta (IL-1beta) and prostaglandin-E2 (PGE2) levels. MATERIAL AND METHODS: In this cohort study, 48 pregnant women without periodontitis were evaluated in the first, second, and third trimesters and at 3 months postpartum. Twenty-eight non-periodontitis non-pregnant women were evaluated twice, with a 6-month interval. Plaque and gingival indices (PlI, GI), salivary progesterone and estradiol and GCF IL-1beta and PGE2 levels were determined. anova for repeated measures or Friedman's test were used for intragroup analyses. Inter-group comparisons were analysed with t-test or Mann-Whitney U-test. Correlations were evaluated with Pearson's and Spearman's test. RESULTS: Pregnant women showed an increase in GI (p<0.05) despite maintaining low PlI values. No changes in IL-1beta and PGE2 levels were observed during pregnancy. No significant correlation was found between the GI increase and salivary hormone levels. GI (p<0.05) and IL-1beta levels (p<0.001) were lower in non-pregnant than in pregnant women. CONCLUSIONS: This study confirms the presence of an exacerbated gingival inflammation during pregnancy, but this phenomenon could not be associated with an increase in progesterone or estradiol or with changes in PGE2 or IL-1beta.

Analysis of new diagnostic methods in suspicious lesions of the oral mucosa.

OBJECTIVE: The objective of this study was to analyse publications related to examination techniques that might improve the visualisation of suspicious lesions of the oral mucosa (ViziLite system and VELscope system) or that might facilitate the cytological identification of suspicious lesions (OralCDx). METHODS: A literature search was performed, using the PubMed database and the key words "brush biopsy", "OralCDx", "ViziLite" and "Velscope", limiting the search to papers in English or Spanish published from 2002 to 2008. RESULTS: According to the results of studies identified, the ViziLite system has a sensitivity of 100% and specificity ranging from 0-14.2%, the VELscope system has a sensitivity of 98-100% and specificity of 94-100% and the Oral CDx system has a sensitivity of 71.4-100% and specificity of 32-100%. CONCLUSION: Clinical examination and histopathological confirmation with biopsy remain the gold standard for the detection of oral cancer. More randomised controlled studies are needed to confirm the positive cost-benefit relationship and the true usefulness of these "new diagnostic methods" in oral mucosal pathology.

Relationship between oral Kaposi 's sarcoma and HAART: contribution of two case reports.

Two HIV infected patients not receiving Highly Active Antiretroviral Treatment (HAART) presented with epidemic Kaposi's sarcoma of the oral cavity. One patient initially refused HAART, but when the lesion became large enough to be noticeable he agreed to HAART associated with excision of the intraoral lesion by CO2 laser. The other patient developed KS and progressed to AIDS at two years after ceasing HAART due to adverse effects; he was referred to hospital for renewed administration of HAART. In both cases, the lesions observed in the oral cavity were the first clinical manifestation of AIDS. These reports underline the close relationship between the use of HAART and the control of KS lesions, highlighting the important role of the dentist in the identification and early diagnosis of these oral lesions.

Cellular senescence in oral cancer and precancer and treatment implications: a review.

INTRODUCTION: Recent studies have demonstrated the capacity of the human organism to prevent the growth of potentially carcinogenic cells by paralyzing them. This antitumor mechanism is known as cellular senescence and is defined as an emergency defence system for cells on the way to becoming cancerous. RESULTS: This review of the literature suggests that oncogene-induced senescence may be a response to oncogenic activation, acting as a natural barrier against tumorigenesis at a premalignant stage. Thus, a large number of cells enter senescence in premalignant lesions but none do so in malignant tumors, due to the loss of senescent pathway effectors such as p16(INK4a) or ARF-p53. Potential senescence markers in oral precancerous lesions include p21(WAF1), p16(INK4a), pRb, Maspin, RAR-beta, G-actin, p15(INK4b), DCR2, and DEC1, some of which are currently under study. CONCLUSION: In the short term, the study of this mechanism may yield valuable data for the management of oral cancer and precancer, for which no effective diagnostic or prognostic markers are yet available.

Gene therapy in the management of oral cancer: review of the literature.

Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions. This review provides an update on transfer techniques, therapeutic strategies, and the clinical applications and limitations of gene therapy in the management of oral cancer and precancer. We highlight the combination of gene therapy with chemotherapy (e.g., 5-Fluoracil) and immunotherapy, given the promising results obtained in the use of adenovirus to act at altered gene level (e.g., p53). Other techniques such as suicide gene therapy, use of oncolytic viruses or the use of antisense RNA have shown positive although very preliminary results. Therefore, further research into these promising gene therapy techniques is required to assess their true efficacy and safety in the management of these lesions.