Salivary anticandidal activity and saliva composition in an HIV-infected cohort

This study investigated salivary anticandidal activity and salivary composition in stimulated whole saliva of 18 advanced HIV-infected patients and compared these values to healthy controls. Stimulated whole saliva from HIV-infected patients showed decreased anticandidal activity. The flow rate was reduced by 40% as compared with controls. The saliva flow rate for HIV-infected patients who had recoverable yeast in their saliva was reduced as compared to HIV-infected patients without recoverable yeast. For HIV-infected patients, the saliva concentrations of lactoferrin, secretory IgA and Cl- were increased while the secretion rate of lysozyme, total protein and K+ were reduced. There was no difference in any parameter as a function of taking the antifungal drug fluconazole. There was no association between salivary anticandidal activity and any salivary component. This study shows reduced anticandidal activity and salivary flow rate in HIV-infected patients. These alterations may contribute to their increased incidence of oral candidal infections.     

Sialochemistry in juvenile idiopathic arthritis

OBJECTIVES: To investigate whether there are any differences in salivary flow rates and saliva composition that may contribute to the reported increase in caries prevalence in patients with juvenile idiopathic arthritis (JIA). DESIGN: Randomized controlled trial. SETTING: The sialochemistry of children with JIA has rarely been investigated. METHODS: Unstimulated and stimulated whole saliva was collected from 17 randomly selected JIA patients and 17 age and sex matched controls. Both samples were analysed for salivary flow rate, pH, calcium and phosphate. RESULTS: Unstimulated and stimulated JIA saliva flow rates, and the flow rate change from unstimulated to stimulated in JIA saliva were all significantly lower than the controls. There were no significant differences in the pH of unstimulated and stimulated JIA saliva compared with the controls, however, the change in pH (from unstimulated to stimulated) in the study group was significantly greater. The JIA patients had non-significantly lower levels of both calcium and phosphate ions in the unstimulated and stimulated samples. CONCLUSIONS: This data would suggest that there is both a reduced resting salivary flow and a reduced response to stimulation in JIA patients, which may contribute to a previously reported higher caries prevalence.     

Detection of Epstein–Barr virus DNA in saliva of HIV‐1‐infected individuals with oral hairy leukoplakia

We present three cases of oral hairy leukoplakia (OHL) in whom the diagnosis was established by EBV DNA detection in whole saliva. Three HIV‐infected patients came to the Oral Medicine Clinic with similar chief complaints of asymptomatic white lesions on the tongue. All patients were diagnosed with suspected OHL and oral thrush also in the first patient. A multiplex PCR DNA microarray was performed to detect EBV DNA in saliva collected by spitting method. All saliva samples showed positive results for EBV DNA, and the definitive diagnosis of OHL was made. Resolution of lesions was found at 1‐ to 2‐month follow‐up after treatment with application of acyclovir 5% cream 5 times daily. Additionally, anti‐fungal treatment was given to the first patient and anti‐retroviral treatment to the first and second patients. EBV is mostly transmitted by asymptomatic shedding into saliva. Therefore, the detection of salivary EBV DNA is useful in establishing a definitive diagnosis of OHL allowing more effective treatment for both HIV‐infected patients receiving ART and treatment‐naïve patients at any CD4 + count.     

Cytokine profiles in parotid saliva from HIV‐1‐infected individuals: changes associated with opportunistic infections in the oral cavity

The purpose of this study was to quantitate levels of cytokines in parotid saliva of subjects infected with human immunodeficiency virus‐1 (HIV‐1) and to determine if the cytokine profiles differ in subjects with an oral opportunistic infection, i.e., candidiasis or oral hairy leukoplakia. Parotid saliva samples were obtained from HIV‐infected individuals with or without candidiasis or oral hairy leukoplakia and from healthy controls and were assessed by ELISA for levels of interleukin (IL)‐1, IL‐2, IL‐4, IL‐5, IL‐10, transforming growth factor‐β, tumor necrosis factor‐α and interferon (IFN)‐γ. Saliva from HIV‐infected subjects with oral candidiasis had significantly higher levels of IFN‐γ than that seen in HIV‐infected individuals with no oral disease and significantly higher levels of IL‐2, IL‐5 and IFN‐γ than saliva of healthy controls. No significant difference was seen in cytokine levels in saliva from HIV‐infected subjects with no oral infections and healthy controls. The HIV‐infected subjects with oral hairy leukoplakia displayed significantly higher levels of both IL‐1α and IFN‐γ compared with the HIV and no oral disease group and a higher level of IFN‐γ than seen in saliva from the healthy control group. In comparing cytokine levels from both HIV and oral disease groups, significant differences were detected in levels of IL‐5 and IL‐10. These results indicate that the profile of salivary cytokines is altered as a result of the oral opportunistic infection candidiasis or oral hairy leukoplakia and also by concurrent HIV infection.     

Salivary secretory leukocyte protease inhibitor increases in HIV infection.

BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is an antimicrobial protein found in saliva and having anti-HIV activity. The concentrations of SLPI in parotid and submandibular/sublingual (SMSL) saliva were determined in an HIV(+) population and compared with uninfected controls. The effect of highly active antiretroviral therapy (HAART) on the concentrations in saliva was determined. METHODS: Stimulated parotid and SMSL saliva was collected from 65 HIV(+) patients and 19 healthy controls. Flow rates, total protein and SLPI concentrations were determined as well as the effect of HAART on these measurements. RESULTS: Mean flow rates were reduced for parotid (64%) and SMSL (44%) saliva of HIV(+) patients. Flow rate reductions were unaffected by HAART. Total protein concentration in HIV(+) parotid saliva was increased 56%; patients on HAART had higher concentrations than control. For both groups, SLPI concentrations of SMSL saliva were twice that of parotid saliva. For HIV(+) patients SLPI concentrations of both saliva types were 70% greater than control; the increase in parotid saliva was greater for those taking HAART. For each saliva type, the secretory rate and specific SLPI protein concentration were not different between the groups. Patients with low CD4(+) counts had greater SLPI concentrations in parotid saliva than control. There was a negative correlation between CD4(+) counts and the SLPI concentration of parotid saliva. CONCLUSIONS: Salivary flow rate is decreased and the concentration of SLPI is increased in the presence of HIV infection. SLPI concentration in parotid and SMSL saliva is greater with HAART.     

Stimulated salivary flow rate, pH and lactobacillus and yeast concentrations in non-smokers and smokers

The effect of smoking habit on flow rate, pH and lactobacillus and yeast counts of paraffin stimulated whole saliva was analyzed in an unmedicated adult population of 462 nonsmokers and 180 smokers. Regular but not immediate smoking was not associated with any significant changes in the salivary flow rate. The pH of stimulated whole saliva was in both sexes lower in smokers than in non-smokers, the differences between the groups being statistically significant. Smoking did not affect salivary yeast counts, but smokers did show increased proportions of high lactobacillus counts.     

Whole stimulated salivary flow in patients with chronic hepatitis C virus infection

BACKGROUND: Salivary gland disorders have been included among the extra-hepatic manifestations related to HCV infection. METHODS: The whole stimulated salivary flow rate (spitting technique) was studied in 74 HCV infected patients to evaluate salivary gland dysfunction. RESULTS: The salivary flow of the patients with chronic HCV infection was similar to that of the healthy controls. The association between subjective xerostomia salivary flow was seen to be very weak. No significant associations were found between salivary flow and age, sex, risk factor of acquired infection, ALT, AST, GGT, ALP values, time lapsed since the diagnosis or HCV-RNA detection in saliva. CONCLUSIONS: Although the functional repercussion of hepatitis C related lymphocytic sialoadenitis remains unclear, we did not find a significant reduction in the whole stimulated salivary flow in HCV infected patients.     

Salivary secretion, mucin concentrations and candida carriage in HIV-infected patients

Objectives:  To test whether the submandibular/sublingual (SMSL) salivary secretion, mucin concentration and candida carriage status were altered in human immunodeficiency virus-positive (HIV+) patients.
Subjects and methods:  SMSL saliva collected from 48 HIV-infected and 31 HIV-negative men were analyzed for flow rates, total protein and mucin concentrations. Salivary cultures were performed for Candida assessment.
Results:  The salivary flow rate and protein secretion of the HIV+ patients was 37% and 32% less than that of the controls ( P  <   0.0001, P  =   0.0087). The mucin concentrations (MG1 and MG2) were higher in the HIV+ subjects compared with controls ( P  =   0.0186, P  =   0.0014); however, the mucin secretions were not different. The frequency of Candida -positive cultures was higher in the HIV+ subjects than in the controls (61.4% vs 24.1%, P  =   0.0018). In the HIV-infected group, the unstimulated SMSL flow rates were lower in Candida -positive than in Candida -negative patients ( P  =   0.0158).
Conclusion:  The salivary secretion of the SMSL glands was reduced in HIV infection. Although the mucin concentration increased in HIV+ subjects, mucin secretion was not altered. Highly active antiviral therapy had no effect on salivary function. We found an association between the level of candida carriage and salivary flow rate in HIV-infected patients.     

Oral manifestations and salivary flow rate, pH, and buffer capacity in patients with end-stage renal disease undergoing hemodialysis.

OBJECTIVE: The aim of this study was to investigate oral manifestations and salivary changes in patients with end-stage renal disease undergoing hemodialysis. STUDY DESIGN: Eighty-two patients undergoing hemodialysis for renal insufficiency were examined; 22 of these patients were randomly selected for salivary tests. Unstimulated whole saliva and stimulated parotid saliva were collected, and flow rate, pH, and buffer capacity were examined. Twenty-two healthy volunteers were included as controls. RESULTS: Uremic odor, dry mouth, and taste change were common symptoms. Petechia and/or ecchymosis and increase of tongue coating were major signs. The flow rates of unstimulated whole and stimulated parotid saliva were decreased in the patient group. The pH and buffer capacity of unstimulated whole saliva were increased in the patient group, but stimulated parotid saliva did not show any significant differences. CONCLUSIONS: Patients with end-stage renal disease undergoing hemodialysis showed apparent oral and salivary changes. The results help us understand the relationship between oral changes and renal insufficiency.     

Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren’s syndrome but decreased by HIV infection

Calprotectin levels were determined in whole saliva from patients predisposed to oral candidiasis due to HIV infection or Sjögren’s syndrome and from patients with candidiasis associated with various oral disorders (e.g. lichen planus, oral ulceration). Mean calprotectin levels were higher in whole saliva (2 μg/ml) than in parotid saliva (0.3 μg/ml). Oral candidiasis was associated with raised whole saliva calprotectin levels in all groups studied. HIV infection was associated with lower levels of salivary calprotectin, in the presence of high or low salivary Candida counts, although CD4⁺ lymphocyte counts did not significantly correlate with calprotectin concentrations. Calprotectin levels were elevated in saliva from Sjögren’s syndrome patients with oral candidiasis, consistent with mucosal transudation of calprotectin from inflamed mucosa and limited dilution due to decreased salivary flow rates. This study indicates that oral candidiasis is associated with raised calprotectin levels secondary to mucosal inflammation, but that diminution of this candidacidal factor due to HIV infection may be a predisposing factor in the aetiology of oral candidiasis.     

Effects of long‐term use of HAART on oral health status of HIV‐infected subjects

J Oral Pathol Med (2010) 39 : 397–406 Background: The aim of this study was to determine the effects of long‐term use of highly active antiretroviral therapy (HAART) on oral health status of HIV‐infected subjects. Methods: Oral examination and measurement of saliva flow rate of both unstimulated and wax‐stimulated whole saliva were performed in HIV‐infected subjects with and without HAART, and in non‐HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long‐term use of HAART on oral health status of HIV‐infected subjects. Results: One hundred and fifty‐seven HIV‐infected subjects – 99 on HAART (age range 23–57 years, mean 39 years) and 58 not on HAART (age range 20–59 years, mean 34 years) – and 50 non‐HIV controls (age range 19–59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV‐infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short‐term HAART (P < 0.01). The subjects with long‐term HAART were found to have a greater risk of having oral lesions than those with short‐term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). Conclusion: We conclude that long‐term HAART has adverse effects on oral health status of HIV‐infected subjects.     

Longitudinal study of parotid saliva in HIV-1 infection

Parotid flow rate and chemistry of 78 HIV+ gay/bisexual men and 27 HIV- gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV+ at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV+ with reduced flow over time. In 6% of HIV+ there was a marked reduction in flow rate and Sjögren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV+ patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins.     

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS)

Objective:  To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS).
Design:  Longitudinal cohort study.
Subjects and methods:  A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands.
Main outcome measures:  Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no).
Results:  Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated ( P  =   0.01) and stimulated ( P  =   0.0004) salivary flow rates as well as salivary gland enlargement ( P  =   0.006) as compared with non-PI based HAART.
Conclusions:  PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.     

Stimulated salivary flow rate, pH and lactobacillus and yeast concentrations in non-smokers and smokers

Abstract – The effect of smoking habit on flow rate, pH and lactobacillus and yeast counts of paraffin stimulated whole saliva was analyzed in an unmedicated adult population of 462 non-smokers and 180 smokers. Regular but not immediate smoking was not associated with any significant changes in the salivary flow rate. The pH of stimulated whole saliva was in both sexes lower in smokers than in non-smokers, the differences between the groups being statistically significant. Smoking did not affect salivary yeast counts, but smokers did show increased proportions of high lactobacillus counts.     

Minor gland and whole saliva in postmenopausal women using a low potency oestrogen (oestriol)

Many women undergo hormone replacement therapy in order to relieve menopausal and postmenopausal symptoms. Oral discomfort is common among these symptoms and studies have shown that the stimulated whole saliva flow rate is increased after combined oestradiol and progesterone replacement therapy. There is, however, no data regarding the effect of other oestrogens or of oestrogen alone on whole and minor gland saliva. In the present study, the flow rate from minor salivary glands (buccal, labial and palatal) and the secretion rate and buffer capacity of whole saliva was examined in 18 postmenopausal women (61-76 years) prior to, and during 1 year of a low potency oestrogen (oestriol) use. The ability of whole saliva to aggregate and mediate bacterial adherence as well as subjective feelings of dry mouth was also examined. For comparison, the same variables were examined in nine peri- and postmenopausal, non-medicated women (reference group, 53-61 years). During hormone treatment, the labial saliva flow was significantly increased and the complaints of dry mouth reduced. Increased stimulated whole saliva flow was seen in both the hormone and reference groups. This was also true for the stimulated whole saliva buffer capacity, which was increased parallel to the flow rate. The secretion rates were generally lower in the hormone group compared to the reference group throughout the study period. Except for stimulated whole saliva, statistical analysis at baseline revealed no age-related reduction of the saliva flow rates. The ability of whole saliva to mediate aggregation of Actinomyces naeslundii was significantly decreased after hormone treatment. Thus, the present findings indicate that a low dose oestrogen (oestriol) may affect the flow rate of labial salivary glands and the bacterial aggregation activity of whole saliva.     

Serum and salivary antibodies to a mycobacterial 65‐kDa stress protein are elevated in HIV‐positive patients and modified by oral candidiasis

Serum immunoglobulin G (IgG) and IgA, and salivary IgA antibodies to a mycobacterial stress protein (mSP65) were determined in human immunodeficiency virus (HIV)–positive patients, acquired immunodeficiency syndrome (AIDS) patients and HIV‐negative controls with or without oral candidiasis. Serum IgG antibodies were elevated in patients with HIV infection and AIDS and especially in subjects with candidiasis compared with controls (P<0.02, P<0.005). This was not apparent with serum IgA. In the absence of candidiasis, salivary IgA antibodies were elevated in HIV‐positive patients compared with AIDS (P<0.005) patients and healthy controls (P=0.001). The relative avidity of serum IgG antibodies to mSP65 in controls with candidiasis was lower than healthy controls (P<0.0001). In saliva there was a decrease in the relative avidity of IgA antibodies in AIDS patients with candidiasis compared with HIV patients (P< 0.03). In patients without candidiasis, the relative avidity was higher in HIV patients than healthy controls (P=0.02). The results suggest that HIV infection leads to raised serum and salivary antibodies to heat shock proteins. Concurrent Candida infection may modify both the titer and relative avidity differently for serum and saliva.     

Changes in whole saliva in patients with coeliac disease

Many systemic diseases impair salivary flow rate and composition and therefore incite oral pathological processes. This study analyses the composition of whole saliva in patients with diagnosed coeliac disease (CD) and in healthy controls, and monitors possible changes in saliva composition after a short oral gluten challenge. Paraffin-stimulated whole saliva was collected from 128 CD patients and 55 healthy controls. In a separate study, paraffin-stimulated whole saliva samples were collected from 33 CD patients and 10 controls both before and 24 h after an oral mucosal and submucosal gluten challenge. No difference in saliva flow rate was observed, but total protein (P相似文献   

Alteration in salivary function in early HIV infection

The etiology of salivary gland hypofunction in HIV(+) patients is unclear. This study was designed to determine the effect of early-stage HIV(+) infection (CD4(+) > 200 cells/ micro L; n = 139) on salivary gland function and the relationship of this dysfunction to the taking of xerostomic medications. Salivary flow rates and the content of electrolytes and antimicrobial proteins in stimulated parotid and submandibular/sublingual saliva were determined. Compared with healthy controls (n = 50), the HIV(+) group showed significant reductions in flow rates of unstimulated whole (35%), stimulated parotid (47%), unstimulated submandibular/sublingual (23%), and stimulated submandibular/sublingual (39%) saliva. The flow rates for the HIV(+) patients taking xerostomic medications did not differ from those of patients who did not. Concentrations of some salivary gland components were altered in the HIV(+) group. Analysis of these data suggests that salivary gland function is adversely affected early in HIV infection and that these changes do not appear to be compounded by the taking of xerostomic medications.     

s-IgA and cytokine levels in whole saliva of Sjögren's syndrome patients before and after oral pilocarpine hydrochloride administration: a pilot study

Previous investigations have found elevated levels of s-IgA in the parotid saliva and normal levels in submandibular saliva of patients with Sjögren's syndrome (SS). Fox et al. also found elevated levels of cytokines (i.e., IL-2 and IL-6) in serum, salivary epithelial cells and parotid saliva of patients with SS. The oral administration of pilocarpine hydrochloride stimulates whole and parotid salivary flow. The purpose of this study was to determine the levels of s-IgA and IL-2 and IL-6 in whole saliva before and after administration of pilocarpine hydrochloride in SS subjects. Ten definitively diagnosed SS subjects were enrolled in the study, as were ten controls (C). The mean age was 57.2 years and all subjects were female. Whole unstimulated saliva (WUS) was collected by standard techniques for 5 min, after which the volume and flow rate were determined (mean WUS: SS = 0.047 vs C = 0.480 ml/min). Samples were centrifuged and the immunoglobulin analysis performed on the supernatants by immunoreactivity in a double-sandwich technique as previously described by Rudney et al. Cytokine analysis was performed similarly utilizing commercially available kits from R&;D Systems. The results as analyzed by pairwise t-tests revealed comparable levels of s-IgA in the saliva of the SS patients, as compared to controls at baseline (means±SEM: SS-IgA = 348.1±82.0 vs C-IgA = 284.0±65.1 μg/ml; NS ). Whole salivary flow was significantly increased (328%) in the SS subject group 60 min after the administration of 5 mg pilocarpine hydrochloride (means±SEM: 0.0472±0.017 vs 0.1546±0.054 ml/min; P<0.01). There was no significant change in the concentration of s-IgA in the SS subject group following the pilocarpine dose (means±SEM: SS-IgA = 439.9±121.2 μl/ml; P = NS). There were elevated levels of IL-2 in the saliva of four out of the ten and IL-6 in two out of the ten SS patients, as compared to controls (means±SEM: SS-IL-2 = 127.8±11.4 vs C-IL-2 = 30.8±1.6 pg/ml and SS-IL-6 = 41.4±7.1 vs C-11.6 ± 2.8 pg/ml). There was also a significant decrease in the concentration of IL-2 in the same four out of ten SS subjects following the pilocarpine dose (means±SEM: SS-IL-2 = 32.4±10.3; P<0.01). These preliminary results indicate that s-IgA levels do not change with increased salivary flow following the administration of pilocarpine hydrochloride in patients with Sjögren's syndrome. While cytokines are elevated in the whole saliva of some SS patients, a decrease in IL-2 concentration may occur with increased salivary flow.