The Beneficial Impact of the Black Chokeberry Extract against the Oxidative Stress in the Sublingual Salivary Gland of Rats Intoxicated with Cadmium.

Cadmium (Cd) is one of the most harmful xenobiotics to which humans are exposed, mainly by the oral route, throughout life. Preventive strategies are searched as low intoxication with this element, among others due to its prooxidative properties, can be deleterious to health and the exposure to it is continuously increasing. Recently, interest has been paid to plant raw materials with a high antioxidative potential to oppose the prooxidative properties of cadmium, such as black chokeberry (Aronia melanocarpa L. fruit), which is rich in polyphenolic compounds. The study was aimed at assessing whether the chokeberry extract may counteract the prooxidative impact of low-level and moderate repeated intoxication with cadmium on the sublingual salivary gland. The investigation was performed on 96 Wistar rats (females), which were treated with a 0.1% aqueous extract from chokeberries or/and a diet containing 1 or 5 mg Cd/kg for 3 and 10 months, and control animals. The intoxication with cadmium, in a dose- and time-dependent manner, attenuated the enzymatic and nonenzymatic antioxidative potential and increased the concentration of hydrogen peroxide and total oxidative status of the sublingual salivary gland resulting in an occurrence of oxidative stress, enhancement of lipid peroxidation, and oxidative injuries of proteins in this salivary gland. The treatment with the black chokeberry extract during the intoxication with cadmium prevented this xenobiotic-caused oxidative/reductive imbalance and oxidative modifications of proteins and lipids in the salivary gland. The above results allow the conclusion that the consumption of black chokeberry products during intoxication with cadmium can prevent oxidative stress and its consequences in the sublingual salivary gland and thus counteract the unfavourable impact of this xenobiotic on the oral cavity.

Effects of estrogen on STIM1/Orai1 in the sublingual gland of ovariectomized rats.

BACKGROUND: Studies have shown that estrogen can protect the function of the sublingual gland, but the specific mechanism is still unclear. Besides, the STIM1/Orai1 pathway is important to secretion in the salivary gland. Here, we explore the possible effects of estrogen on sublingual gland function by observing changes of STIM1 and Orai1 levels in the sublingual glands of ovariectomized rats. METHODS: 42 adult female Sprague-Dawley rats were randomly divided into three groups: SHAM, OVX, and OVX+E (n = 14 per group). Two weeks after ovariectomy, rats were treated with estrogen (ß-estradiol). The expression of STIM1 and Orai1 in the sublingual gland were observed by double label-immunohistochemistry and immunofluorescence. Calcium imaging was conducted to observe changes in cellular Ca²âº levels. RESULTS: IHC and IF showed that the levels of both STIM1 and Orai1 decreased following ovariectomy, but increased to SHAM levels after estrogen treatment. By IF, STIM1 and Orai1 exhibited perfect co-localization. Calcium imaging results showed that the Ca²âº in the cells decreased after ovariectomy. Estrogen intervention returned levels of these proteins and Ca²âº to the same as those in the control group. CONCLUSION: This study demonstrates that low estrogen status significantly reduced the expression of STIM1 and Orai1 in the sublingual gland of rats, along with cellular Ca²âº levels. These data provide insight into the likely mechanisms underlying sublingual gland secretion dysfunction during menopause.

Pefloxacin induced changes in serotonergic innervation and mast cell number in rat salivary glands.

Pefloxacin is a second-generation fluoroquinolone antibiotic. Besides its advantageous characteristics, side effects including the hypofunction of salivary glands, decreased saliva production, and peripheral neuropathy were observed during the administration of pefloxacin. The aim of this study was to investigate the changes in the number of serotonergic immunoreactive fibers and mast cells after pefloxacin treatment in the parotid and sublingual glands of rats to detect the possible neurotoxic effect of pefloxacin. The adult female rats were treated with intraperitoneal (i.p.) injection of pefloxacin for three or seven days (at a concentration of 20 mg/100g body weight) and the serotonergic innervation pattern along with the change in mast cell number were evaluated by using histochemistry and immunohistochemistry in the parotid and sublingual glands. We found that a three-day treatment significantly increased the number of immunoreactive serotonergic nerve fibers, but after a seven-day treatment the number of serotonin positive nerve fibers decreased almost to values of the control group. The alteration of mast cell number was parallel with the changes of the serotonin positive fibers during the treatment. These results suggest that pefloxacin treatment can modify the finely controlled communication between the immune- and the peripheral nervous systems, resulting neurogenic inflammatory process. The background of this process is the altered serotonergic innervation and the increased number of activated mast cells releasing different mediators for example histamine, which can finally lead to reduced number of serotonin positive nerve fibers after a seven-day treatment of pefloxacin leading to atrophy and hypofunction of the salivary glands.

Hyposalivation due to chemotherapy exacerbates oral ulcerative mucositis and delays its healing.

OBJECTIVES: Cancer therapy including chemotherapy causes gland atrophy, resulting in low salivary secretion in cancer patients. Since saliva plays an important role in oral health, the dysfunction may exacerbate oral ulcerative mucositis (OUM), which is another side effect. Here, we investigated the effect of hyposalivation on OUM using sialoadenectomized rats and examined the effects of anticancer drugs on the salivary glands. DESIGN: As models for hyposalivation, the bilateral submandibular and sublingual glands except (2EXT) or together with (3EXT) the parotid glands were extracted. At 16 days after the procedure, OUM was experimentally developed by topical acetic acid treatment on the labial fornix region of the inferior incisors, and the severity and bacterial loading level were evaluated. The salivary gland weights and histology were analyzed after administration of the representative anticancer drugs 5-fluorouracil or cisplatin. RESULTS: The severity of OUM was greater in both the 3EXT and 2EXT rats and delayed the healing process compared with that in sham rats without salivary gland extraction. The healing process in the 3EXT rats was longer than that in the 2EXT rats. The number of colony-forming units in the ulcerative region from the 3EXT rats was 10-fold greater than that in the sham rats. Both 5-fluorouracil and cisplatin reduced glands weights and damaged the salivary glands. CONCLUSIONS: These results suggest that chemotherapy-induced hyposalivation exacerbates OUM and delays healing, most likely due to loss of salivary clearance and antimicrobial functions. This study illustrates the significance of oral health care for cancer patients undergoing chemotherapy.

Physiological cAMP-elevating secretagogues differentially regulate fluid and protein secretions in mouse submandibular and sublingual glands.

The mechanisms underlying the functional differences in sympathetic and parasympathetic regulation of the major salivary glands have received little attention. The acute effects of parasympathetic muscarinic (carbachol)-dependent and combined parasympathetic-dependent plus cAMP-dependent pathways on fluid secretion rates, ion composition, and protein content were assessed using a newly developed ex vivo preparation that allows the simultaneous perfusion of the mouse submandibular (SMGs) and sublingual glands (SLGs). Our results confirm that the muscarinic-dependent pathway accounts for the bulk of salivation in SMGs and SLGs, whereas costimulation with a cAMP-increasing agent (forskolin, isoproterenol, or vasoactive intestinal peptide) did not increase the flow rate. Costimulation with carbachol plus the ß-adrenergic agonist isoproterenol decreased the concentration of NaCl and produced a substantial increase in the protein and Ca2+ content of SMG but not SLG saliva, consistent with a sparse sympathetic innervation of the SLGs. On the other hand, forskolin, which bypasses receptors to increase intracellular cAMP by directly activating the enzyme adenylate cyclase, enhanced the secretion of protein and Ca2+ by both the SMGs and SLGs. In contrast, isoproterenol and vasoactive intestinal peptide specifically stimulated protein secretion in SMG and SLG salivas, respectively. In summary, cAMP-dependent signaling does not play a major role in the stimulation of fluid secretion in SMGs and SLGs, whereas each cAMP-increasing agonist behaves differently in a gland-specific manner suggesting differential expression of G protein-coupled receptors in the epithelial cells of SMGs and SLGs.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis.

To beta block or not to beta block; that is the question.

The fast-acting ß-1 blocker esmolol has been the center of attention since the landmark article by Morrelli and colleagues suggesting that, in patients with sepsis, reducing heart rate by administering esmolol can result in a survival benefit. However, the use of esmolol for the treatment of sepsis and the underlying mechanism responsible for this benefit remain controversial. This commentary discusses the study by Jacquet-Lagrèze and colleagues, who in a pig model of sepsis tested the hypothesis that administration of esmolol to reduce heart rate may correct sepsis-induced sublingual and gut microcirculatory alterations which are known to be associated with adverse outcome.

Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model.

INTRODUCTION: Esmolol may efficiently reduce heart rate (HR) and decrease mortality during septic shock. An improvement of microcirculation dissociated from its macrocirculatory effect may a role. The present study investigated the effect of esmolol on gut and sublingual microcirculation in a resuscitated piglet model of septic shock. METHODS: Fourteen piglets, anesthetized and mechanically ventilated, received a suspension of live Pseudomonas aeruginosa. They were randomly assigned to two groups: the esmolol (E) group received an infusion of esmolol, started at 7.5 µg⋅kg(-1)⋅min(-1), and progressively increased to achieve a HR below 90 beats⋅min(-1). The control (C) group received an infusion of Ringer's lactate solution. HR, mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), arterio-venous blood gas and lactate were recorded. Oxygen consumption (VO2), delivery (DO2) and peripheral extraction (O2ER) were computed. Following an ileostomy, a laser Doppler probe was applied on ileal mucosa to monitor gut microcirculatory laser Doppler flow (GMLDF). Videomicroscopy was also used on ileal mucosa and sublingual areas to evaluate mean flow index (MFI), heterogeneity, ratio of perfused villi and proportion of perfused vessels. Resuscitation maneuvers were performed following a defined algorithm. RESULTS: Bacterial infusion induced a significant alteration of the gut microcirculation with an increase in HR. Esmolol produced a significant time/group effect with a decrease in HR (P <0.004) and an increase in SVR (P <0.004). Time/group effect was not significant for CI and MAP, but there was a clear trend toward a decrease in CI and MAP in the E group. Time/group effect was not significant for SI, O2ER, DO2, VO2, GMLDF and lactate. A significant time/group effect of ileal microcirculation was found with a lower ileal villi perfusion (P <0.025) in the C group, and a trend toward a better MFI in the E group. No difference between both groups was found regarding microcirculatory parameters in the sublingual area. CONCLUSIONS: Esmolol provided a maintenance of microcirculation during sepsis despite its negative effects on macrocirculation. Some parameters even showed a trend toward an improvement of the microcirculation in the gut area in the esmolol group.

Functional differences in the acinar cells of the murine major salivary glands.

In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl(-)-dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca(2+)] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl(-) efflux and the protein levels of the Ca(2+)-activated Cl(-) channel TMEM16A, the major apical Cl(-) efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na(+)-K(+)-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl(-) uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl(-) movement, including the transporter activities of the Cl(-) uptake and efflux pathways, and intracellular Ca(2+) mobilization.

mRNA expression and localization of LPS-induced ß-defensin isoforms in rat salivary glands.

ß-defensins are small, cationic peptides with broad-spectrum antimicrobial activity that are produced by mucosal epithelia. However, little is known about the expression of ß-defensins in the major salivary glands. The purpose of this study was to characterize expression of rat ß-defensin-1 (RBD-1) and -2 (RBD-2) mRNA within the major salivary glands together with the effect of injection of intraductal lipopolysaccharide (LPS) on that expression. ß-defensin mRNA expression was quantitated by RT-PCR in salivary gland tissues and salivary acinar and striated duct cells collected by laser captured microdissection. RBD-1 and -2 were expressed in the parotid gland, the submandibular gland, and the sublingual gland. ß-defensins were expressed in both the acinar and striated duct cells of the major salivary glands. Intraductal injection of LPS increased expression of RBD-1 and -2 mRNA, which peaked at 12 hrs. These results suggest that salivary cells (acinar and striated duct cells) have the potential to produce ß-defensins.

[An evaluation of the radioprotective effect of vitamin E on the salivary glands of radioactive iodine in rats]. / Radyoaktif iyot verilen siçanlarda tükürük bezleri üzerinde E vitaminin radyasyondan koruyucu etkisinin degerlendirilmesi.

OBJECTIVES: This study aims to examine the acute effect of vitamin E on salivary gland of radioactive iodine (RAI; 131I)-induced rats and to evaluate whether vitamin E have a radioprotective effect. MATERIALS AND METHODS: Sixteen Wistar albino rats were used in the study. The rats were divided into two groups. The first group was administered (131)I orally and 1 ml physiological saline. The second group was administered (131)I and 1 ml vitamin E intraperitoneally. Vitamin E was started two days before the RAI therapy and continued for seven days. On the eighth day, salivary glands were removed and evaluated histopathologically. RESULTS: There was no statistically significant difference between the groups. The changes in the interstitial space of all glands and in acinar epithelial cells of parotid and sublingual glands were observed in a lower number of the rats of vitamin E group, compared to the controls. Except panacinar inflammation, histopathological changes in acinar epithelial cells of the submandibular gland were noticed in a lower number of the rats of vitamin E group. CONCLUSION: Considering the changes in the interstitial space and acinar epithelial cells in a lower number of the rats of vitamin E group, we conclude that vitamin E may have protective effects for interstitial space of all glands and acinar epithelial cells of the parotid and sublingual glands during the acute period.

Effects of glucocorticoid on postnatal development of rat sublingual glands.

Hormones have been reported to be involved in salivary gland's growth and development, but few studies have investigated the effects of glucocorticoids on the morphology of the sublingual glands around the weaning period. The objective of this study was to ascertain the effects of glucocorticoid administration on rat sublingual glands around the weaning period. Male Wistar rats were administered triamcinolone, a glucocorticoid, once every other day from 8 days after birth (experimental group). A control group was given vehicle only. The sublingual glands were then extracted at 15, 20, 25, and 30 days after birth. Samples thus obtained were subjected to Alcian blue and periodic acid-Schiff staining, lectin staining, and immunohistochemical staining to assess cellular proliferative potential. And acinar cell circumferences were measured. We found that glucocorticoid had no effect on the production of acid or neutral mucopolysaccharides by acinar cells around the weaning period. Glucocorticoid administration resulted in hypertrophy of acinar cells between 15 and 30 days after birth. Early appearance of changes in α-mannose, α-glucosamine, and N-acetylglucosamine in secretory granules suggested that glucocorticoid may have acted to promote cell differentiation. The glucocorticoid had no effect on the proliferative potential of sublingual gland acinar cells around the weaning period.

An immunohistochemistry-based study on aquaporin (AQP)-1, 3, 4, 5 and 8 in the parotid glands, submandibular glands and sublingual glands of Sjögren's syndrome mouse models chronically administered cevimeline.

Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that produce saliva are destroyed. Cevimeline is thought to affect the composition of saliva in part by regulating the localization of aquaporins (AQPs). In this study, we investigated the effects of chronic Cevimeline administration in the salivary glands of SS mice on the immunohistochemical localization of aquaporin (AQP)-1, 3, 4, 5 and 8. We used Cevimeline-untreated SS mice, treated SS mice, discontinued SS mice and untreated normal mice. AQP-5 was found in the apical and lateral membranes of acinar cells in the parotid and submandibular glands of cevimeline-treated SS mice and untreated normal mice. Saliva secretion and AQP-5 localization were sustained in SS mice who were chronically administered Cevimeline and at four weeks after discontinuation. Unlike AQP-5, the localization of AQP-1, 3, 4 and 8 were not affected by Cevimeline administration. Our findings demonstrated that administration of Cevimeline maintains the proper localization of AQP-5 in the acinar cells of the salivary gland, which may promote salivation in chronically treated SS mice. Clinically, this suggests that chronic Cevimeline administration may be useful therapeutically for SS patients suffering from a decrease in saliva secretion by improving the disordered AQP-5 localization.

CD38/ADP-ribosyl cyclase in the rat sublingual gland: subcellular localization under resting and saliva-secreting conditions.

CD38 is a 42-45 kDa transmembrane glycoprotein that exhibits ADP-ribosyl cyclase enzyme activity. In the rat, we have previously reported strong ADP-ribosyl cyclase activity in the sublingual salivary gland (Masuda W. and Noguchi T. Biochem. Biophys. Res. Commun. (2000) 270, 469-472). Here, we have examined the specific localization of CD38/ADP-ribosyl cyclase activity in this gland and whether that localization changes upon saliva-secretary stimulation. Under resting conditions, CD38/ADP-ribosyl cyclase activity in the post-nuclear fraction of SLG homogenates was separated into two major peaks by sucrose density gradient centrifugation. The first peak included the plasma membrane proteins Na+/K+ ATPase and aquaporin 5, while the second peak included mucous secretory protein mucin and vesicle-associated membrane protein 2. When rats were subjected to the muscarinic agonist pilocarpine, the CD38/ADP-ribosyl cyclase activity disappeared from the second peak, as did mucin and vesicle-associated membrane protein 2. Pre-treatment of rats with the muscarinic antagonist atropine before pilocarpine administration, or adrenergic stimulation with isoproterenol, the sucrose density gradient separation profiles were same as that seen under resting condition. Using an immunofluorescent strategy, we observed the preferential localization of CD38 in the basolateral plasma membrane and intracellular granule-like membrane in sublingual acinar cells under resting conditions.

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.

Different role of isoproterenol and NOS inhibitors on salivary ducts of rats.

OBJECTIVES: Nitric oxide (NO) is a diffusible intracellular messenger that is present in saliva. Chronic treatment with isoproterenol, a beta receptor agonist, stimulates the release of NO from acinar cells and induces salivary gland hypertrophy. The aim of this study was to investigate the effect of NO synthesis inhibitors and isoproterenol on rat salivary glands. We analyzed salivary gland weight and the number of ducts per unit area (0.5mm(2)) by NADPH-diaphorase histochemistry (to identify the presence of the enzyme NO synthase-NOS) and haematoxylin-and-eosin (HE). METHODS: For 8 days male Wistar rats received daily single intraperitoneal injections of saline or a NOS inhibitor (40mg/kg N(omega)-nitro-L-arginine L-NOARG or N(omega)-nitro-l-arginine methyl ester L-NAME). This was followed, 30min later, by subcutaneous injection of isoproterenol (2 or 5mg/kg) or saline. RESULTS: Isoproterenol increased parotid and submandibular gland weights. Isoproterenol (2mg/kg) induced a decrease of ducts per unit area inversely correlated to the weight of the parotid gland. This effect was augmented by L-NAME. In the submandibular gland L-NAME attenuated isoproterenol (2mg/kg) weight increase. In the submandibular gland isoproterenol and NOS inhibitors induced an increase in ducts per unit area (HE and NADPH-diaphorase). No effect was observed in the sublingual gland. CONCLUSION: To our knowledge this is the first description of isoproterenol and NOS inhibitors increasing duct density in the submandibular gland. Our results corroborate the hypothesis that NO plays different roles in parotid and submandibular glands.

Major salivary gland output differs between users and non-users of specific medication categories.

BACKGROUND: The intake of medications is a major aetiologic factor of xerostomia. The purpose of this study was to investigate the selective influence of medication categories on flow rates of individual major salivary glands. METHODS: The effect of each medication category on salivary flow rates was determined by dichotomy comparisons between users and non-users. A total of 246 patients were included, 79 males and 167 females aged 13-92 years (mean 63 years). Of these, 200 used medications, which were grouped according to their category. A comprehensive medical and oral examination was performed. Both unstimulated and stimulated saliva was collected separately from the parotid and submandibular/sublingual glands. RESULTS: Parotid flow rate was decreased among users of tranquillisers and sedatives (unstimulated flow), cardiovascular drugs and gastrointestinal drugs (stimulated flow). Submandibular/sublingual unstimulated output was lower in patients taking cardiovascular drugs, antihistamines, tranquillisers/sedatives and antidepressants, while the stimulated flow, in those taking cardiovascular drugs, antihistamines, tranquillisers/sedatives and gastrointestinal drugs. CONCLUSIONS: Users of many common medication categories display significantly reduced unstimulated and/or stimulated salivary flow rate from the major salivary glands compared with non-users. A larger number of medication categories are associated with reductions in salivary flow rate from submandibular/sublingual glands than parotid glands.

Leptin modulates the detrimental effect of Porphyromonas gingivalis lipopolysaccharide-induced cytosolic phospholipase A2 activation on salivary mucin synthesis via ERK-signal transduction.

Activation of cytosolic phospholipase A2 (cPLA2) by bacterial LPS is considered a key step in the generation of proinflammatory lipid messengers, including platelet-activating factor (PAF), recognized as the most proximal mediator of inflammatory events triggered by bacterial infection. In this study, we report on the role of leptin in modulation of the detrimental consequences of cPLA2 activation in salivary gland acinar cells by the LPS of a periodontopathic bacterium, P. gingivalis. Employing mucous cells of rat sublingual gland, we show that the LPS-induced cPLA2 activation is associated with up-regulation in PAF generation and the impairment in mucin synthesis, and was subject to suppression by leptin. A potentiation in the countering capacity of leptin on the LPS-induced arachidonic acid release and PAF generation was attained in the presence of ERK inhibitor, PD98059, while the PI3K inhibitor, wortmannin had no effect. However, the prevention by leptin of the LPS detrimental effect on mucin synthesis was subject to suppression by the inhibitors of both PI3K and ERK. Moreover, amplification in the effect of leptin on the LPS-induced decrease in mucin synthesis was attained with cPLA2 inhibitor, MAFP as well as PAF receptor antagonist, BN52020, while the reversal of the leptin effect occurred in the presence of exogenous PAF. These findings demonstrate the involvement of leptin in countering the pathological consequences of cPLA2 activation by P. gingivalis LPS on salivary mucin synthesis through the involvement in MAPK/ERK and PI3K signaling events.