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Biomedical subjects

Rafael M Nagler

Publications and source records attributed to Rafael M Nagler.

At least 19 recordsLinked to original sources
PubMed2007

Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile.

BACKGROUND: Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which induce oxidative and nitrative stress, are main contributors to oral carcinogenesis. The RNS (nitrosamines: nitrates, NO(3), and nitrites, NO(2)) are also produced by the reaction of ROS and other free radicals with nitric oxide (NO) and are therefore in equilibrium with it. METHODS: Whole saliva was collected from a group of 25 consenting oral squamous cell carcinoma (OSCC) patients and from a control group of 25 healthy age- and gender-matched individuals. General and specific salivary antioxidant components, salivary nitrosamines, and oxidatively damaged salivary DNA and proteins were measured. RESULTS: The findings showed that oxidative and nitrative stress altered the salivary composition in OSCC patients. Analyzed salivary RNS were substantially higher (NO, 60%; NO(2), 190%; NO(3), 93%), whereas all salivary antioxidants were substantially reduced. The 8-hydroxy-deoxyguanosine (8-OHdG) marker (a widely used indicator of DNA oxidation) increased by 65% and the salivary carbonylation level was significantly higher. CONCLUSIONS: The increase in ROS and RNS may have been the event that led to the consumption and reduction of salivary antioxidant systems, thus explaining the oxidative damage to the DNA and proteins, and possibly the promotion of OSCC. The oxidized proteins and DNA found in the saliva of the cancer patients seems to be the first demonstration of a direct link between salivary free radicals, antioxidants, and OSCC. This may be important for better understanding the pathogenesis of the disease and may contribute to its diagnosis and treatment.

Adult↗
PubMed2006

Effects of diabetes mellitus, chronic renal failure and hemodialysis on serum and salivary antioxidant status.

AIM: To analyze various oxidative stress parameters in the saliva and serum of patients with chronic renal failure (CRF) and/or diabetes mellitus (DM), and to compare them in dialytic vs. pre-dialytic patients. METHOD: 50 consenting patients were divided into five subgroups of patients: severe CRF (dialytic) without DM, severe CRF (dialytic) with DM, mild CRF (pre-dialytic) without DM, mild CRF (pre-dialytic) with DM, and with DM but without CRF (controls). Uric acid (UA), peroxidase and total antioxidant status (TAS) were studied in both saliva and serum; superoxide dismutase (SOD) was evaluated only in saliva. Both saliva collection and serum harvesting were done simultaneously. RESULTS: In severe-CRF patients without DM, median TAS, UA and SOD levels decreased following dialysis (54, 85, 48%, respectively), and peroxidase levels increased slightly (9%). In severe-CRF patients with DM, median TAS and SOD levels increased following dialysis (33 and 54%, respectively) while median UA and peroxidase levels decreased (68 and 10%, respectively). CONCLUSIONS: DM, CRF and hemodialysis were found to increase the oxidative stress burden in both serum and saliva. Therefore, antioxidant assessment may be used to monitor baseline oxidative status in these situations though larger randomized studies are in order.

Aged↗
PubMed2006

Oxidative stress indices in COPD--Broncho-alveolar lavage and salivary analysis.

OBJECTIVE: It has been suggested that oxidative stress plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD), though this role has yet to be fully elucidated. The purpose of this study was to further evaluate this role as concomitantly expressed in the saliva and broncho-alveolar lavage (BAL/'lavage'). DESIGN: Forty consenting patients (mean age 62+/-13-year-old), with/without COPD and/or smoking habit, participated in the study. The following antioxidant profile was examined both in saliva and lavage of the patients: total antioxidant status (TAS), uric acid (UA), peroxidase and super oxide dismutase (SOD). Total protein (TP) and albumin (Alb) were also evaluated in both saliva and lavage while amylase was measured only in saliva. RESULTS: Increase of TAS (by 100%) and of SOD activity levels (by 60%) in the lavage of COPD patients indicated oxidative stress. The salivary UA in COPD patients was 125% higher (p = 0.05) while the peroxidase was 20% higher. Another novel finding was that levels of salivary antioxidants in smoking versus non-smoking COPD patients were lower by 25-48% (for all four: TAS, UA, peroxidase and SOD) while the albumin was significantly reduced by 60% (p = 0.018). CONCLUSION: Oxidative-stress-related changes demonstrated both in the lavage and saliva of the COPD and/or smoking patient indicate cumulative effects of both, also emphasizing the pathogenetic role of free radicals in COPD. Salivary analysis, which is less invasive and much easier to perform as compared with lavage analysis, is suggested as a new and effective diagnostic tool in COPD patients.

Adult↗
PubMed2006

Free radicals related effects and antioxidants in saliva and serum of adolescents with Type 1 diabetes mellitus.

OBJECTIVE: The purpose of the current study was to analyze both serum and salivary composition and oxidative stress markers in Type 1 diabetes mellitus (DM) patients. DESIGN: Twenty consenting patients with DM but otherwise healthy patients aged 13-19 years and 12 healthy controls, matching in age and gender (Group 1), participated in the study. The patients were divided according to those who had controlled diabetes mellitus (Group 2) or uncontrolled diabetes mellitus (Group 3). All were analyzed for saliva composition and antioxidants. Saliva was also analyzed for its levels of superoxide dismutase (SOD) and amylase activity, total IgA and total IgG concentrations and potassium, phosphorus, magnesium and calcium electrolyte concentrations. RESULTS: A significant correlation was found between the severity of the DM/HbA1c values and the increase in both salivary and/or serum antioxidants (peroxidase, SOD and TAS), and the various TCL parameters (H1, H3, pre-incubation and oxygenation-potential). CONCLUSIONS: The two most important findings of the current study relate to the role of oxidative stress in the pathogenesis of Type 1 diabetes mellitus and to the involvement of salivary glands in the disease. The profound effects of DM on salivary antioxidant parameters may be also of great importance in respect to the diagnosis and evaluation of the disease. The correlation between altered salivary parameters and the severity of the disease may indicate that evaluation of the salivary status of DM patients as part of the assessment of their disease activity and severity is warranted.

Adolescent↗
PubMed2006

Salivary oxidative stress in children during acute asthmatic attack and during remission.

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells, which may contribute to its pathogenesis. Saliva analysis is non-invasive and friendly to children. We undertook this study to analyze the salivary oxidative profile and composition in children with asthma during attack and remission, and to compare them with the levels of salivary antioxidants of healthy control children. METHODS: School age (range 6-18 years) children referred to the emergency room for acute asthma were included. Clinical score was assessed, spirometry performed, and saliva samples were collected and analyzed. All measurements were repeated during remission of asthma attack (2-4 weeks after attack). Salivary analysis was performed blindly during asthma attack and the results were compared to those obtained during remission, and to those of the control group. RESULTS: Statistically significant decreases in levels of salivary peroxidase enzyme activity were observed in asthmatic children during attack compared with healthy controls, with partial recovery during remission of attack. Similarly decreased levels of calcium concentrations were observed in asthmatic children, accompanied by increased phosphate levels. CONCLUSIONS: Children with acute asthma attacks exhibit a decrease in the activity of the most important salivary antioxidant enzyme-peroxidase, which is accompanied by other salivary composition alterations. Hence, acute asthma is manifested by salivary changes. This implies systemic oxidative stress in asthma, which may be reflected in salivary analysis.

Acute Disease↗
PubMed2005

Age-related changes in unstimulated salivary function and composition and its relations to medications and oral sensorial complaints.

BACKGROUND AND AIMS: The purpose of the current study was to examine the salivary flow rate and composition in relation to drug consumption and idiopathic oral sensorial complaints (OSC). OSC cover xerostomia, disturbed sense of taste, or burning mouth sensitivity with no established classical etiology (e.g., Sjogren's syndrome, or a response to radiotherapy). METHODS: A thorough sialometrical and sialochemical analysis was performed for all subjects who were healthy non-hospitalized individuals ranging in age from 18-89 years. Saliva samples were all collected in unstimulated conditions. RESULTS: The three most significant observations were: a) Elderly people have significantly reduced and altered salivary secretion. Whereas specific concentrations increased, the total values of most salivary components were found to be decreased in the elderly. b) Fifty percent of the elderly make OSC. c) OSC were made mainly by elderly individuals who use drugs. CONCLUSIONS: Reduction in salivary function and altered composition are age-related. However, when drugs are not involved, a compensatory capacity which avoids OSC apparently exists. In contrast, the effect of drugs on OSC is extensive. The finding that the total amount of salivary components and not only salivary flow rates are reduced in the elderly is of great clinical importance, since such a reduction is expected to be reflected in compromising various salivary functions.

Administration, Oral↗
PubMed2005

Relationships between age, drugs, oral sensorial complaints and salivary profile.

The aim of this study was to investigate the relationships between oral sensorial complaints (OSCs) and salivary flow rate, composition and drug consumption of subjects aged 18-90 years. The results were correlated with both drug consumption and OSCs. Only individuals who were free of conditions that are already known to cause OSCs were included in the study. The three most significant observations were as follows: (1) elderly people have significantly reduced and altered salivary secretion compared with younger people. While specific concentrations increased, the total values of most salivary components decreased in the elderly; (2) 50% of the elderly population have OSCs regarding taste, burning mouth syndrome or xerostomia; and (3) OSCs were more prevalent in elderly people who use drugs than in those who do not. In conclusion, a reduction in salivary function and altered composition are age related. A compensatory capacity that prevents OSCs appears to exist in elderly patients who do not use drugs, but drugs were found to have an extensive effect on OSCs. The finding that the total amounts of salivary components and not only the salivary flow rate were reduced in elderly people is of great clinical relevance, since such a reduction is expected to be reflected in compromising various salivary functions.

Adolescent↗
PubMed2005

Association between regional idiopathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints.

UNLABELLED: The idiopathic sensorial disturbances of burning mouth syndrome (BMS), taste disturbances (dysgeusia), and dry mouth (xerostomia) have recently been recognized as one entity and given the generic name of oral sensorial complaints (OSC). However, not all patients with OSC complain of all three disturbances, and the underlying mechanism of OSC has not yet been elucidated. This study sought to determine whether OSC was associated with the alteration of oral sensory perception, salivary profile and/or personality traits. It examined 35 patients with OSC and 19 controls. Sensory perception was assessed by Quantitative Sensory Testing (QST) applied to the tongue, including thresholds for thermal sensations and pain, and the magnitude estimation of tonic suprathreshold heat pain stimuli. The salivary profile included flow rate and compositional analysis. Personality traits were examined by both state and trait anxiety and somatization scoring. Results showed significantly elevated thermal sensory thresholds and decreased pain scores for tonic heat pain. In addition, there was an increased level of somatization in the OSC group as compared to the control group (15.1 +/- 1.5 vs. 6.6 +/- 2.1, respectively; P = .003). Concomitantly, altered salivary composition (elevated Na, K, Cl, Ca, IgA, and amylase concentrations)-but not salivary flow rate reduction-was observed in those patients despite their complaints of oral dryness. All parameters were similar among the patients with OSC regardless of their type of complaint. Linear regression analysis revealed that an elevated warm sensory threshold was associated with higher levels of salivary K and Cl concentrations in the patients with OSC. These findings may be attributed to a regional small fiber idiopathic neuropathy affecting oral sensation and salivary secretion in OSC. Alternatively, a primary idiopathic salivary dysfunction might cause sensory neural dysfunction at the receptor level by changing the oral cavity milieu. PERSPECTIVE: Based on the salivary, psychophysical, and personality traits analysis currently presented, as well as on the available literature, we hypothesize that a comprehensive mechanism for OSC is based on a regional neuropathy, which is expressed by complaints of BMS, taste disturbances, and/or xerostomia. All are clearly distinguishable from similar conditions with established organic/therapeutic-related etiologies.

Adult↗
PubMed2005

Oropharyngeal cancer pathogenesis: ubiquitin proteolytic, apoptotic and epidermal growth factor related pathways act in concert--first report.

The current study was carried out to examine the clinical characteristics and survival-probability rates of 51 patients treated for oral (tongue) cancer and to correlate it with various tumor markers. The clinical data and survival probability rates were correlated with the immunohistological analysis of p27, Skp2, p53, Bcl-2, TUNEL (apoptotic rate) and c-erbB-2 markers. The 5-year survival-probability correlated with staging, grading and base of tongue location. An inverse relation between the expression of p27 and Skp2, p27 and grading, and a direct relation between Skp2 and grading were demonstrated. Concomitantly, significant correlations between low p27, high Skp2 and high TUNEL (apoptotic rate) expressions and between low p27 and high c-erbB-2 (Her2) expressions in the cancer lesions were demonstrated. The accumulated data may be employed in the future for a better understanding of the biology behind oral cancer and for developing better means of detection and treatment.

Adult↗
PubMed2004

Biochemical analysis of saliva and taste acuity evaluation in patients with burning mouth syndrome, xerostomia and/or gustatory disturbances.

OBJECTIVE: In the current study, we performed taste and salivary analysis on patients suffering from burning mouth syndrome and xerostomia or taste disturbances. STUDY DESIGN: A total of 180 patients who complained of idiopathic burning mouth syndrome (BMS) and taste aberrations and/or xerostomia that may accompany BMS were evaluated. These patients were compared with 90 healthy, age- and sex-matched controls. Salivary flow rate, biochemical and immunological analysis and taste acuity by the forced-choice drop technique were performed for all subjects. These analyses were found to be conclusive in distinguishing controls from patients with complaints. RESULTS: The great similarity of both salivary and taste analysis in the BMS, taste aberration and xerostomia groups, which were significantly different from the results obtained in the control group, was found to be the most striking result. Higher salivary concentrations in the experimental group were consistent with a lower saliva (water) flow rate. CONCLUSION: An oral neuropathy and/or neurological transduction interruption induced by salivary compositional alterations is suggested as the possible aetiology for the complaints. This report may add an important objective diagnostic tool to the clinician treating these patients.

Adolescent↗
PubMed2004

Synergistic effect of cigarette smoke and saliva on lymphocytes--the mediatory role of volatile aldehydes and redox active iron and the possible implications for oral cancer.

Oral squamous cell carcinoma (SCC) is most induced by exposure of the oral epithelial cells to tobacco products such as cigarette smoke. This exposure always occurs in the presence of saliva and presumably is induced by free radicals. To explore the effects of CS on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to CS, alone or in the presence of saliva. We discovered that after 80min, exposure of the lymphocytes to CS alone resulted in a time-dependent cellular loss with a survival rate of 56%, while following lymphocyte exposure to CS in the presence of saliva, less than 15% of the cells survived. This was accompanied by concomitant accumulation of cellular protein carbonyls which could be protected by the exogenous addition of uric acid or glutathione, but not by the addition of ascorbate (Asc), N-acetyl-l-cystein (NAC) or desferal (DES). Exposure of the lymphocytes to aldehydes present in CS, such as acrolein and croton-aldehyde, also resulted in the elevation of protein carbonyls, which was ameliorated primarily by the addition of glutathione. However, lymphocyte exposure to acroline in the presence of saliva did not show the same synergism in cell death observed as when the lymphocytes were exposed to CS and saliva. Thus, we postulated the existence of another mechanism and examined the role of redox active iron as an additional explanation for this synergism. In fact, it was found that in the presence of saliva and ascorbate there was a marked decrease in the lymphocyte survival rate; this was reversed by the addition of the iron chelator desferal. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested, stressing the role of a pivotal player in the process leading to oral cancer which has never been previously considered in this regard - the saliva.

Adult↗
PubMed2004

Lethal synergistic effect of cigarette smoke and saliva in an in vitro model: does saliva have a role in the development of oral cancer?

Exposure of oral mucosal cells to cigarette smoke induces oral cancer, presumably via the injurious effect of free radicals. To explore the effects of cigarette smoke on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to cigarette smoke, alone or in the presence of saliva. After 80 min exposure to cigarette smoke alone, a time-dependent cellular loss and survival rate of 52% was observed. By contrast, following the exposure of the lymphocytes to cigarette smoke in the presence of saliva, less than 20% of the cells survived. Saliva secreted from the submandibular/sublingual (Sm/Sl) glands was highly cytotoxic, while saliva secreted from the parotid glands was only moderately cytotoxic. Redox active iron ions in saliva and aldehydes in cigarette smoke were shown to play the major injurious roles in this synergistic phenomenon. The salivary-borne redox active iron ions participate in Fenton and Haber-Weiss reactions to transform low-reactive free radicals, which originate from cigarette smoke into highly-reactive .OH(-)-free radicals. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested where saliva may be a pivotal player.

Adult↗
PubMed2004

Sialochemical and gustatory analysis in patients with oral sensory complaints.

UNLABELLED: Our objective was to perform concomitant taste and salivary analyses in subjects with oral sensory complaints (OSC), including burning mouth syndrome (BMS), idiopathic taste aberrations, and xerostomia without established etiology, to attempt to find a possible explanation for the mechanism underlying those complaints. BMS is a disorder characterized by a painful burning or scalding sensation in clinically normal and healthy oral mucosa. Taste and salivary analyses were performed on 163 subjects with OSC who complained of BMS, taste aberration, or xerostomia, alone or in combination. These subjects were compared with 84 healthy, age- and sex-matched control subjects. The salivary and taste analyses were found to be helpful in distinguishing control subjects from complaining subjects. The most striking result found was the great similarity of both salivary and taste analyses in the BMS, taste aberration, and xerostomia groups, which were significantly different from the results obtained in the control group. An oral neuropathy or neurologic transduction interruption induced by salivary compositional alterations is suggested as the possible etiology for the complaints. This report might add an important objective diagnostic tool to the clinician treating such patients. PERSPECTIVE: The merit of the current study stems from the fact that it suggests for the first time a salivary-related local neuropathic mechanism for oral sensorial complaints. This may be of paramount importance, both with respect to the biological background of these complaints and to the possible therapeutic modalities that might be offered to suffering patients.

Adolescent↗
PubMed2003

Effect of cigarette smoke on oral peroxidase activity in human saliva: role of hydrogen cyanide.

Peroxidase activity in human saliva is composed of salivary peroxidase (80%), of salivary glandular origin, and myeloperoxidase (20%), of leukocyte origin. The term oral peroxidase (OPO) is used here to denote the total activity of both peroxidase species. Using the 2-nitrobenzoic acid-thiocyanate assay, OPO activity was measured in the saliva of nonsmokers after exposure to gas-phase cigarette smoke (CS) in an in vitro system using three puffs of CS in 1 h. A marked decrease of 76% of activity was observed following three puffs of CS. In order to elucidate the mechanism by which CS caused loss of OPO activity, several oxidants and antioxidants were applied to saliva in vitro in the presence and absence of CS. No protection for CS-induced loss of OPO activity occurred in the presence of glutathione, N-acetylcysteine, ascorbic acid, or Desferal. Exposure of saliva to purified aldehydes present in CS did not significantly affect OPO loss of activity. Similarly, ascorbic acid in the presence of FeCl(3) and nicotine also had no effect on OPO activity. Exposure of OPO to cyanate at levels present in CS caused a 65-70% loss of OPO activity, which was reversible after 24 h of dialysis. Moreover, hydroxocobalamin, a known cyanate chelator, could prevent CS- and potassium cyanide-induced inactivation of OPO by 70-90%. The results show that hydrogen cyanide, known to be present in microgram amounts per cigarette, is likely to be the species in CS responsible for loss of salivary OPO activity. The finding of reduced salivary OPO levels after CS exposure may represent a contributory mechanism for CS-related compromises in antimicrobial defenses in the aerodigestive tract.

Antioxidants↗
PubMed2003

Inhibition of oral peroxidase activity by cigarette smoke: in vivo and in vitro studies.

Oral peroxidase (OPO), the pivotal enzyme in the salivary antioxidant system, seems to be of paramount importance in the oral defense mechanism, especially against the attack of free radicals related to cigarette smoke (CS) and the evolution of oral cancer. The major inducer of oral cancer is exposure to tobacco, which is responsible for 50-90% of cases worldwide. The purpose of our study was to elucidate the outcome of interaction between CS and OPO in smokers and nonsmokers. After smoking a single cigarette, a sharp drop of OPO activity was observed in both groups: 42.5% in smokers and 58.5% in nonsmokers (p <.05). After 30 min, the level of activity returned to 90-100% of the presmoking level, presumably due to the secretion of new saliva into the oral cavity. The difference between the two groups was also observed after exposure of saliva to one cigarette in smoking flasks (in vitro studies); however, as expected, no recovery of activity was observed in either group. Similarly, the OPO activity loss was accompanied by increased carbonylation of the salivary proteins, an indicator of the oxidative damage to proteins. These results may be of great clinical importance, as heavy smokers smoke 20 cigarettes or more on a daily basis. Accordingly, most of the time the oral epithelium of heavy smokers is essentially unprotected by OPO against the deleterious effects of thiocyanate ions and hydroxyl radicals produced by unremoved hydrogen peroxide in the presence of the salivary redox-active metal ions. This may pave the way for the CS-induced and saliva-mediated initiation and progression of oral cancer.

Antioxidants↗
PubMed2003

Prognostic role of apoptotic, Bcl-2, c-erbB-2 and p53 tumor markers in salivary gland malignancies.

OBJECTIVE: The clinical characteristics and survival probability rate of 36 patients with salivary gland malignancies and 10 patients with benign salivary tumors were summarized in relation to the immunohistological analysis of the tumor, apoptotic-related markers and apoptosis rate. The expression of the markers examined - Bcl-2, c-erbB-2, p53 - was detected in paraffin sections of the tumors by the streptavidin-biotin peroxidase method following heat-induced antigen retrieval, and the apoptosis rate was determined by the TUNEL method. RESULTS: The overall 5-year survival probability was 61% for patients with malignant tumors and 100% for those with benign tumors. The survival probability of patients over 60 at diagnosis was significantly lower than that of younger patients. Patients whose malignant tumors were larger than 2 cm at diagnosis had worse survival than those with smaller tumors. The survival probability of patients whose malignant tumors were located in the submandibular glands was significantly lower than that of patients whose malignancies were located in the parotid and minor salivary glands. The survival probability of patients who demonstrated positive staining for c-erbB- 2 or TUNEL was lower than for those with negative staining. Gender, the existence of concomitant non-salivary malignancies and ethnic origin had no significant impact on survival. CONCLUSIONS: Our results demonstrated significant positive staining in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue examined for TUNEL, c-erbB-2, Bcl-2 and p53, pointing to a biological role for all four markers in the tumorigenic process which is yet to be elucidated. Significant reduction in survival was related to the specific location of the tumor in the submandibular gland, its size and older age of patient. Survival was also found to be significantly reduced when positive staining was demonstrated in the tumor tissue for TUNEL or c-erbB-2, more so for concomitant positive staining of both markers. Clinically, the most important result of the current study is that the survival rate of the patients examined with salivary tumors larger than 2 cm, with positive staining for both TUNEL and c-erbB-2, was 0 (p = 0.0001)!

Adolescent↗