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1.
Rheumatology (Oxford) ; 59(4): 742-753, 2020 04 01.
Article in English | MEDLINE | ID: mdl-31377809

ABSTRACT

OBJECTIVES: Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. METHODS: Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-α or IFN-γ and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-κB subunit), TNF-α, IL-1ß, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. RESULTS: MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-α and IFN-γ, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. CONCLUSION: Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.


Subject(s)
Acinar Cells/drug effects , Endoplasmic Reticulum Stress/drug effects , Mucin-1/drug effects , Salivary Glands, Minor/drug effects , Sjogren's Syndrome/metabolism , Submandibular Gland/drug effects , Taurochenodeoxycholic Acid/pharmacology , Xerostomia/metabolism , Acinar Cells/metabolism , Adult , Aged , Case-Control Studies , Cells, Cultured , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/genetics , Female , Heat-Shock Proteins/drug effects , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Immunoprecipitation , In Vitro Techniques , Interferon-gamma/pharmacology , Interleukin-1beta/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Membrane Proteins/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle Aged , Mucin-1/genetics , Mucin-1/metabolism , Mucins/drug effects , Mucins/genetics , Mucins/metabolism , Proteins/drug effects , Proteins/genetics , Proteins/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Salivary Glands, Minor/metabolism , Salivary Proteins and Peptides/drug effects , Salivary Proteins and Peptides/genetics , Salivary Proteins and Peptides/metabolism , Sjogren's Syndrome/genetics , Submandibular Gland/cytology , Submandibular Gland/metabolism , Transcription Factor RelA/drug effects , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Xerostomia/genetics
2.
J Clin Pediatr Dent ; 39(4): 377-81, 2015.
Article in English | MEDLINE | ID: mdl-26161611

ABSTRACT

UNLABELLED: Secretory IgA is the main type of immunoglobulin in saliva and is considered to be the main secretion factor of adaptive immunity in the mouth. OBJECTIVE: To assess the effect of Anti Retroviral Therapy on SIgA levels in saliva of HIV infected children. STUDY DESIGN: A cross-sectional sample of 50 HIV infected children aged 6-8 years were divided into 2 groups ; Group 1: children prior to onset of anti-retroviral therapy and Group 2: children undergoing anti-retroviral therapy. Stimulated whole saliva samples were collected from each child following I hour of breakfast. The samples were placed on ice packs and immediately transferred to a laboratory, processed and total SIgA quantification was estimated using ELISA. Data obtained was statistically analyzed. RESULTS: Among HIV infected children, significantly low SIgA levels of 6.2 mg/dl was seen in children prior to ART. CONCLUSION: Salivary IgA levels were significantly low in HIV infected children, particularly in children prior to ART.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Immunoglobulin A, Secretory/drug effects , Saliva/drug effects , Salivary Proteins and Peptides/drug effects , CD4 Lymphocyte Count , Child , Cross-Sectional Studies , DMF Index , Dental Caries/immunology , HIV Infections/immunology , Humans , Immunoglobulin A, Secretory/analysis , Saliva/immunology , Salivary Proteins and Peptides/analysis
3.
PLoS One ; 10(3): e0119666, 2015.
Article in English | MEDLINE | ID: mdl-25742511

ABSTRACT

Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito-parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins may play a role in regulating mosquito biting behavior patterns and may have implications in the development of malaria parasites in resistant mosquitoes during parasite transmission.


Subject(s)
Anopheles/drug effects , Insecticides/pharmacology , Nitriles/pharmacology , Pyrethrins/pharmacology , Salivary Glands/drug effects , Salivary Proteins and Peptides/metabolism , Animals , Anopheles/classification , Anopheles/metabolism , Female , Gene Expression Regulation/drug effects , Insect Proteins/drug effects , Insect Proteins/metabolism , Insecticide Resistance , Proteomics , Salivary Glands/metabolism , Salivary Proteins and Peptides/drug effects
4.
Int J Oral Sci ; 5(4): 217-23, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24158141

ABSTRACT

Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands.


Subject(s)
Botulinum Toxins, Type A/pharmacology , Neuromuscular Agents/pharmacology , Saliva/drug effects , Submandibular Gland/drug effects , Amylases/drug effects , Animals , Apoptosis/drug effects , Aquaporin 5/antagonists & inhibitors , Cell Membrane/drug effects , In Situ Nick-End Labeling , Male , Microscopy, Electron, Transmission , Organ Size , Rabbits , Random Allocation , Receptor, Muscarinic M3/antagonists & inhibitors , Saliva/metabolism , Salivary Proteins and Peptides/drug effects , Salivation/drug effects , Secretory Rate/drug effects , Secretory Vesicles/drug effects , Submandibular Gland/metabolism , Submandibular Gland/pathology , Time Factors
5.
Arch Oral Biol ; 57(9): 1200-10, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22541734

ABSTRACT

During eating, human saliva is secreted into the oral cavity by salivary glands. The relative contribution of different glands to total salivary flow rate depends, among other factors, on the tastants in the food. Few reports indicated that also the salivary protein composition depends on the tastant make-up of the food. We studied the influence of sodium-chloride- and sucrose solutions on the presence of proteins in the M(r) range 2-20kDa in whole saliva. Upon oral stimulation with a sodium chloride solution, a sucrose solution or water, we collected whole saliva from 14 volunteers after t=1 min, t=11 min and t=20 min. Saliva protein profiles were analysed by SELDI-TOF-MS. SELDI-TOF-MS intensities of m/z values representing different protein masses were compared between subjects, tastants and time conditions. For subsets of the 33 detected masses, significant effects were observed for all factors, with most masses involved in the Subjects effect: m/z(Subjects)>m/z(Time×Stimulus)>m/z(Stimulus)>m/z(Time). Most effects on saliva protein composition were observed at t=1 min, whilst almost no effects were observed at t=11 min and t=20 min. When considering the Stimulus×Time interaction, we identified four different stimulus-response patterns. Proteins identified in the present study, and attributed to specific glands or tissues in literature, were used to associate stimulus-response patterns with tissue provenances. Observed stimulus-response patterns were not uniquely associated to particular glands and tissues. Hence, there was no evidence of the involvement of particular tissues or glands in tastant-specific protein responses. In conclusion, oral stimulation with different tastants affects salivary protein composition in a protein- and stimuli dependent way, which seems not be associated with any specific tissues or glands of origin.


Subject(s)
Saliva/drug effects , Salivary Proteins and Peptides/drug effects , Sodium Chloride/pharmacology , Sucrose/pharmacology , Taste/physiology , Adult , Cystatins/analysis , Female , Follow-Up Studies , Histatins/analysis , Humans , Male , Middle Aged , Molecular Weight , Muramidase/analysis , Parotid Gland/metabolism , Peptide Fragments/analysis , Peptide Fragments/drug effects , Protein Array Analysis , Reaction Time , S100 Proteins/analysis , S100A12 Protein , Saliva/chemistry , Saliva/metabolism , Salivary Proline-Rich Proteins/analysis , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Sublingual Gland/metabolism , Submandibular Gland/metabolism , Young Adult , alpha-Defensins/analysis
6.
Arch Oral Biol ; 56(4): 395-400, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21112044

ABSTRACT

Pilocarpine induces a profuse flow of saliva, and it may re-establish saliva production in cases of drug-induced oral dryness. The aim of the study (a sub-study to the previous trial investigating the pilocarpine fluid effects in individuals suffering from drug-induced dry mouth) was to search for saliva quality changes induced by the treatments. Sixty-five individuals were enrolled in a randomized, double-blind, placebo-controlled trial. The subjects received tramadol to induce oral dryness. Secretion rate was measured before and after tramadol, and then after pilocarpine, placebo, or no treatment. All saliva was analyzed for its protein and IgA content in the pilocarpine (n=15) and placebo groups (n=12). At baseline, the flow of saliva was 0.47±0.05ml/min, the protein output 0.17±0.2mg/min and the IgA output 0.022±0.002mg/min. After tramadol treatment (50mg 3×/day over two days), the flow was reduced by 64%, protein output by 52% and the IgA output by 38%. While placebo treatment did not affect any of the variables, the flow was 120%, the protein output 193% and the IgA output 83% of the baseline characteristics after pilocarpine treatment (5mg). Thus, the pilocarpine-induced increase in the flow rate in the state of tramadol-induced oral dryness results in saliva with a well preserved protein concentration but with a decrease in IgA concentration. However, compared to baseline, there was neither a decrease in output nor in concentration of IgA.


Subject(s)
Muscarinic Agonists/pharmacology , Pilocarpine/pharmacology , Saliva/metabolism , Salivary Proteins and Peptides/drug effects , Salivation/drug effects , Xerostomia/drug therapy , Analysis of Variance , Humans , Immunoglobulin A/metabolism , Narcotics , Saliva/drug effects , Salivary Proteins and Peptides/metabolism , Tramadol , Xerostomia/chemically induced
7.
Braz. j. med. biol. res ; 43(12): 1143-1152, Dec. 2010. ilus
Article in English | LILACS | ID: lil-569006

ABSTRACT

5-Bromo-2’-deoxyuridine (BrdUrd) has long been known to interfere with cell differentiation. We found that treatment ofBradysia hygida larvae with BrdUrd during DNA puff anlage formation in the polytene chromosomes of the salivary gland S1 region noticeably affects anlage morphology. However, it does not affect subsequent metamorphosis to the adult stage. The chromatin of the chromosomal sites that would normally form DNA puffs remains very compact and DNA puff expansion does not occur with administration of 4 to 8 mM BrdUrd. Injection of BrdUrd at different ages provoked a gradient of compaction of the DNA puff chromatin, leading to the formation of very small to almost normal puffs. By immunodetection, we show that the analogue is preferentially incorporated into the DNA puff anlages. When BrdUrd is injected in a mixture with thymidine, it is not incorporated into the DNA, and normal DNA puffs form. Therefore, incorporation of this analogue into the amplified DNA seems to be the cause of this extreme compaction. Autoradiographic experiments and silver grains counting showed that this treatment decreases the efficiency of RNA synthesis at DNA puff anlages.


Subject(s)
Animals , Bromodeoxyuridine/pharmacology , DNA , Diptera/genetics , Insect Proteins/drug effects , Salivary Glands/chemistry , Salivary Proteins and Peptides/drug effects , Autoradiography , Cell Differentiation , Insect Proteins/genetics , Larva/drug effects , Salivary Glands/drug effects , Salivary Proteins and Peptides/genetics
8.
Braz J Med Biol Res ; 43(12): 1143-52, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21085898

ABSTRACT

5-Bromo-2'-deoxyuridine (BrdUrd) has long been known to interfere with cell differentiation. We found that treatment of Bradysia hygida larvae with BrdUrd during DNA puff anlage formation in the polytene chromosomes of the salivary gland S1 region noticeably affects anlage morphology. However, it does not affect subsequent metamorphosis to the adult stage. The chromatin of the chromosomal sites that would normally form DNA puffs remains very compact and DNA puff expansion does not occur with administration of 4 to 8 mM BrdUrd. Injection of BrdUrd at different ages provoked a gradient of compaction of the DNA puff chromatin, leading to the formation of very small to almost normal puffs. By immunodetection, we show that the analogue is preferentially incorporated into the DNA puff anlages. When BrdUrd is injected in a mixture with thymidine, it is not incorporated into the DNA, and normal DNA puffs form. Therefore, incorporation of this analogue into the amplified DNA seems to be the cause of this extreme compaction. Autoradiographic experiments and silver grains counting showed that this treatment decreases the efficiency of RNA synthesis at DNA puff anlages.


Subject(s)
Bromodeoxyuridine/pharmacology , DNA/drug effects , Diptera/genetics , Insect Proteins/drug effects , Salivary Glands/chemistry , Salivary Proteins and Peptides/drug effects , Animals , Autoradiography , Cell Differentiation , Insect Proteins/genetics , Larva/drug effects , Salivary Glands/drug effects , Salivary Proteins and Peptides/genetics
9.
Arch Oral Biol ; 55(7): 470-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20593553

ABSTRACT

OBJECTIVE: The aim of the present study was to assess the null hypothesis that the astringency and loss of lubrication in the oral cavity are not related to the properties of the epigallocatechin-3-gallate (EGCG) adlayer, the affinity and the entropy-drive of EGCG binding to saliva. METHODS: The mass, thickness, and viscoelasticity of the EGCG adlayer and the temperature dependence of EGCG adsorption onto saliva surfaces were determined by quartz crystal microbalance with dissipation (QCM-D). The affinities of EGCG to human whole saliva (WS) and to parotid saliva (PS) were carried out by QCM-D monitoring and fluorescence quenching. RESULTS: The stiffer and more compact EGCG adlayers were formed on saliva surfaces at various concentrations of EGCG. The affinity for EGCG binding to WS was higher than that to PS. The precipitation of EGCG/saliva was temperature-dependent. The driving force of EGCG binding to saliva is dominated by the hydrogen bond, the hydrophobic reaction, and the entropy-drive, which were confirmed by the FTIR spectra and the measurement of temperature- dependence, respectively. CONCLUSION: The viscoelasticity of the EGCG adlayer, the affinity of EGCG to saliva, and the priority of EGCG binding to hydrophobic proteins on the mucosa may account for the oral astringency and loss of lubrication.


Subject(s)
Astringents/pharmacology , Catechin/analogs & derivatives , Protease Inhibitors/pharmacology , Saliva/drug effects , Salivary Proteins and Peptides/drug effects , Urokinase-Type Plasminogen Activator/antagonists & inhibitors , Adsorption , Adult , Astringents/chemistry , Catechin/chemistry , Catechin/pharmacology , Chemical Precipitation , Elasticity , Entropy , Female , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Immobilized Proteins , Lubrication , Male , Middle Aged , Parotid Gland/metabolism , Protease Inhibitors/chemistry , Protein Binding , Salivary Glands/metabolism , Salivary Proteins and Peptides/chemistry , Spectroscopy, Fourier Transform Infrared , Temperature , Viscosity , Young Adult
10.
Arch Oral Biol ; 55(7): 479-85, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20510163

ABSTRACT

OBJECTIVE: To evaluate the effect of astaxanthin on antioxidant parameters of salivary gland from diabetic rats. The hypothesis of the study was whether the supplementation of diabetic rats with astaxanthin might antagonize, or at least prevent, the defect in their antioxidative status. DESIGN: Wistar rats (n=32) were divided in 4 groups: untreated control, treated control, untreated diabetic and treated diabetic rats. Astaxanthin (20mg/kg body weight) was administered daily by gavage for 30 days. On day 23, diabetes was induced by injection of alloxan (60 mg/kg body weight). After 7 days of diabetes induction, the rats were killed and submandibular and parotid removed. Superoxide dismutase (SOD), catalase, glutathione peroxidase and reductase activities and the content of thiol groups were determined. Data were compared by ANOVA and the Tukey test (p<0.05). RESULTS: Diabetes caused a reduction of SOD, and thiol content and increase of catalase and glutathione peroxidase activities of submandibular gland whilst in the parotid gland diabetes caused an increase of thiol content and no effect in the antioxidant system. The astaxanthin restores the enzymatic activities in the salivary gland, however does not prevent its oxidative damage. CONCLUSION: The submandibular gland presented more susceptibility to oxidative alterations induced by diabetes. Astaxanthin presented a positive effect on the oxidative protection of the salivary gland from diabetic rats.


Subject(s)
Antioxidants/therapeutic use , Diabetes Mellitus, Experimental/prevention & control , Parotid Gland/drug effects , Submandibular Gland/drug effects , Alloxan , Animals , Antioxidants/analysis , Catalase/analysis , Catalase/drug effects , Diabetes Mellitus, Experimental/enzymology , Free Radical Scavengers/analysis , Glutathione Peroxidase/analysis , Glutathione Peroxidase/drug effects , Glutathione Reductase/analysis , Glutathione Reductase/drug effects , Male , Parotid Gland/enzymology , Rats , Rats, Wistar , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Submandibular Gland/enzymology , Sulfhydryl Compounds/analysis , Superoxide Dismutase/analysis , Superoxide Dismutase/drug effects , Xanthophylls/therapeutic use
11.
Oral Dis ; 16(8): 801-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20561219

ABSTRACT

OBJECTIVE: In this study we investigated the activity of the nitric oxide synthase (NOS) in parotid glands from rats with experimental periodontitis and controls. METHODS: Periodontitis was produced by a ligature placed around the cervix of the two lower first molar. Experiments were carried out 22 days after the ligature. RESULTS: Ligation caused an increase in parotid NOS activity. The selective blocker of the inducible isoform of the enzyme partially inhibited its activity in parotid glands from rat with ligature. In controls, the activity was partially inhibited by the antagonists of the selective neural and endothelial isoforms. NOS activity in rats with ligature was cyclic adenosine monophosphate (cAMP)-dependent while in controls it was calcium-dependent. Prostaglandin E2 concentration was increased in parotid gland from rats with ligature. The inhibitor of prostaglandin production, FR 122047, diminished both, prostaglandin production and NOS activity. In rats with ligature unstimulated amylase released is increased. Both, prostaglandin and NOS were involved in the increment of amylase release. CONCLUSION: It can be concluded that in parotid glands from ligated rats, prostaglandin E2 production is increased and, through cAMP accumulation, activates the inducible NOS isoform. The increment of nitric oxide production participates in the increase in basal amylase release.


Subject(s)
Nitric Oxide Synthase/metabolism , Parotid Gland/enzymology , Periodontitis/enzymology , Salivary Proteins and Peptides/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Amylases/metabolism , Animals , Calcium/pharmacology , Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/antagonists & inhibitors , Dinoprostone/metabolism , Disease Models, Animal , Egtazic Acid/pharmacology , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Indazoles/pharmacology , Indomethacin/pharmacology , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type I/antagonists & inhibitors , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type III/antagonists & inhibitors , Organ Size , Ornithine/analogs & derivatives , Ornithine/pharmacology , Parotid Gland/drug effects , Piperazines/pharmacology , Prostaglandin-Endoperoxide Synthases/drug effects , Rats , Rats, Wistar , Salivary Proteins and Peptides/drug effects , Thiazoles/pharmacology , omega-N-Methylarginine/pharmacology
12.
Eur J Oral Sci ; 117(3): 218-23, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19583747

ABSTRACT

Amphetamine induces xerogenic effects, but its mechanism of action and xerogenic potency are unknown. In the current in vivo study on the rat parotid gland, the effects of amphetamine on reflex-evoked and acetylcholine-evoked salivation were examined in the absence and presence of adrenergic and dopaminergic antagonists. Under anaesthesia, amphetamine increased the secretion of salivary fluid and the amount of protein therein in response to acetylcholine. Phentolamine abolished the increase in salivary flow and had no effect on the salivary protein concentration, whereas propranolol only reduced the salivary protein concentration. Reflex activation of the secretion evoked a well-maintained level of secretion that was reduced by amphetamine [50% inhibitory dose (ID(50)) 1.9 +/- 0.1 mg kg(-1) intravenously); the salivary protein concentration was increased in the presence of amphetamine. Phentolamine and haloperidol reduced the amphetamine-inhibitory effect on the reflex-evoked fluid response, whereas propranolol had no effect on the fluid response. The xerogenic effect of amphetamine is mainly exerted by central mechanisms involving alpha-adrenoceptors, while, indirectly, amphetamine causes secretion of protein by inducing the release of noradrenaline from glandular nerve terminals.


Subject(s)
Adrenergic Agents/pharmacology , Amphetamine/pharmacology , Parotid Gland/drug effects , Saliva/drug effects , Acetylcholine/pharmacology , Adrenergic Antagonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Cholinergic Agents/pharmacology , Citric Acid/pharmacology , Dopamine Antagonists/pharmacology , Female , Haloperidol/pharmacology , Nerve Endings/drug effects , Norepinephrine/metabolism , Parotid Gland/innervation , Parotid Gland/metabolism , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Rats, Sprague-Dawley , Reflex/drug effects , Saliva/metabolism , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Salivation/drug effects , Secretory Rate/drug effects
13.
Arch Oral Biol ; 54(8): 730-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19473651

ABSTRACT

Xerostomia is commonly caused by antidepressant drugs and ATP can influence the saliva production. Adenosine is the product of extracellular hydrolysis of adenine nucleotides in submandibular gland cells, which occurs by the action of ectonucleotidases. In this study, we have evaluated the effect of three different antidepressants in ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP1-3) activities in cultured cells from salivary glands. Rats received imipramine (10mg/ml), fluoxetine (20mg/ml) or moclobemide (30mg/ml) by oral gavage. The drugs were administered once a day for 14 days. Our results have shown that the hydrolysis of p-nitrophenyl-5'-thymidine monophosphate increased in all treatments. These effects were not consequence of transcriptional control of E-NPP1-3 genes. The results reported here can highlight the importance of ectonucleotidases in the most common side effect caused by antidepressant therapy.


Subject(s)
Antidepressive Agents/pharmacology , Phosphoric Diester Hydrolases/drug effects , Pyrophosphatases/drug effects , Submandibular Gland/enzymology , Animals , Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Cells, Cultured , Fluoxetine/pharmacology , Hydrolysis , Imipramine/pharmacology , Male , Moclobemide/pharmacology , Phosphoric Diester Hydrolases/analysis , Phosphorylation , Pyrophosphatases/analysis , Rats , Rats, Wistar , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Submandibular Gland/cytology , Submandibular Gland/drug effects , Thymidine Monophosphate/analogs & derivatives , Thymidine Monophosphate/analysis , Time Factors
14.
J Dent ; 37(6): 449-53, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19342147

ABSTRACT

OBJECTIVE: The aim was to evaluate the antibacterial effect of ozone on cariogenic bacterial species with and without the presence of saliva and a possible effect on the salivary proteins. METHODS: Suspensions of Actinomyces naeslundii (ACTCC 12104(T)), Lactobacilli casei (N CTC 151) and Streptococcus mutans (NCTC 10449), in salt buffer or in saliva, were exposed to ozone gas delivered by the ozone generator Healozone 2130C. Aliquots of the suspensions were taken after 10, 30 and 60s ozone exposures and cultivated on agar plates. Initial number of bacteria per ml was 8.0 x 10(7) (SD 2.2 x 10(7)) (A. naeslundii), 1.0 x 10(8) (SD 3.1 x 10(6)) (L. casei) and 1.0 x 10(8) (SD 7.0 x 10(5)) (S. mutans), respectively. The proteins were separated by SDS electrophoresis and visualized by silver staining. RESULTS: In salt buffer 92%, 73% and 64% of the initial numbers of A. naeslundii, S. mutans and L. casei, respectively, were killed already after 10s ozone exposure, while approximately 99.9% of the bacteria were dead after a 60s exposure. After 10 and 30s, but not after 60s exposure to ozone, S. mutans and L. casei were less efficiently killed in saliva compared to the salt buffer. Various saliva proteins were degraded by ozone after a 60s exposure. CONCLUSIONS: The cariogenic species S. mutans, L. casei and A. naeslundii were almost eliminated following 60s of ozone treatment. This killing was reduced in the presence of saliva although increasing the ozone application time to 60s overcame these reductants in saliva. Detection of altered salivary proteins indicates that saliva components constitute additional targets for ozone.


Subject(s)
Anti-Bacterial Agents/pharmacology , Dental Caries/microbiology , Gram-Positive Bacteria/drug effects , Oxidants, Photochemical/pharmacology , Ozone/pharmacology , Actinomyces/drug effects , Buffers , Colony Count, Microbial , Electrophoresis, Polyacrylamide Gel , Humans , Lacticaseibacillus casei/drug effects , Saliva/microbiology , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Silver Staining , Sodium Chloride , Streptococcus mutans/drug effects , Time Factors
15.
Indian J Dent Res ; 19(3): 213-8, 2008.
Article in English | MEDLINE | ID: mdl-18797097

ABSTRACT

OBJECTIVE: The objective of the present study was to evaluate early and late effects of radiation and a-tocopherol on the secretion rate of saliva and on selected saliva salivary parameters in oral cavity cancer patients. PATIENTS & METHODS: Eighty-nine histologically confirmed oral cavity cancer patients (OCC) were enrolled in the study. Resting whole saliva was collected before, during and at the end of the radiation therapy (RT) and simultaneous supplementation with alpha - tocopherol to the radiation treated patients (RT + AT). RESULTS: Salivary flow rate, pH, amylase activity, total protein, sodium and potassium were analyzed. Increased pH, potassium and decreased flow rate, amylase activity, protein content and sodium were observed in 6 weeks of radiation treated patients when compared to OCC patients. A significant improvement of those parameters was observed on alpha - tocopherol supplementation in RT + AT patients. CONCLUSION: Supplementation with alpha - tocopherol improves the salivary flow rate thereby, maintains salivary parameters.


Subject(s)
Amylases/radiation effects , Antioxidants/therapeutic use , Mouth Neoplasms/radiotherapy , Saliva/radiation effects , Salivary Proteins and Peptides/radiation effects , alpha-Tocopherol/therapeutic use , Adult , Aged , Amylases/drug effects , Cobalt Radioisotopes/therapeutic use , Electrolytes/analysis , Electrolytes/radiation effects , Female , Follow-Up Studies , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Mouth Neoplasms/drug therapy , Potassium/analysis , Potassium/radiation effects , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , Saliva/drug effects , Salivary Proteins and Peptides/drug effects , Secretory Rate/drug effects , Secretory Rate/radiation effects , Sodium/analysis , Sodium/radiation effects , Xerostomia/etiology , Xerostomia/prevention & control
16.
J Urol ; 180(2): 760-6, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18554633

ABSTRACT

PURPOSE: Several reports suggest that the rat Vcsa1 gene is down-regulated in models of erectile dysfunction. The Vcsa protein product sialorphin is an endogenous neutral endopeptidase inhibitor and its down-regulation could result in prolonged activation of G-protein activated signaling pathways by their peptide agonists. We investigated whether Vcsa1 down-regulation could result in an adaptive change in GPCR (G-protein coupled receptor) expression. MATERIALS AND METHODS: Gene expression in cultured rat corporeal smooth muscle cells following treatment with siRNA directed against Vcsa1 or the neutral endopeptidase gene was analyzed using microarray and quantitative reverse transcriptase-polymerase chain reaction. In rats Vcsa1 is one of the most down-regulated genes following bilateral transection of the cavernous nerves. In that animal model we also investigated whether Vcsa1 down-regulation was accompanied by similar changes in gene expression in corporeal smooth muscle cells in which Vcsa1 was knocked down in vitro. RESULTS: Microarray analysis and quantitative reverse transcriptase-polymerase chain reaction demonstrated that corporeal smooth muscle cells treated in vitro with siRNA against Vcsa1 resulted in GPCR up-regulation as a functional group. In contrast, treatment of corporeal smooth muscle cells that lowered neutral endopeptidase activity resulted in decreased GPCR expression. These results suggest that the peptide product of Vcsa1, sialorphin, can effect GPCR expression by acting on neutral endopeptidase. In animals with bilaterally transected cavernous nerves the decreased Vcsa1 expression is accompanied by increased GPCR expression in cavernous tissue. CONCLUSIONS: These experiments suggest that the mechanism by which Vcsa1 modulates erectile function is partly mediated through changes in GPCR expression.


Subject(s)
Neprilysin/antagonists & inhibitors , Penile Erection/drug effects , Penile Erection/genetics , Receptors, G-Protein-Coupled/metabolism , Salivary Proteins and Peptides/pharmacology , Animals , Cells, Cultured , Disease Models, Animal , Down-Regulation , Gene Expression Regulation/drug effects , Male , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/physiology , Penile Erection/physiology , Probability , Protein Precursors/drug effects , Protein Precursors/metabolism , Random Allocation , Rats , Rats, Inbred F344 , Reference Values , Reverse Transcriptase Polymerase Chain Reaction , Salivary Proteins and Peptides/drug effects , Salivary Proteins and Peptides/metabolism , Sensitivity and Specificity
17.
Arch Oral Biol ; 52(6): 507-17, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17174266

ABSTRACT

We characterized a cDNA clone derived from the female mouse submandibular gland (SMG). The transcript of this cDNA was approximately 1.2kb in size and predicted to code a 165-amino acid protein with a putative signal peptide for a secretory pathway. This protein, named submandibular androgen-repressed protein (SMARP), had homology in the N-terminal region with members of the glutamine/glutamic acid-rich protein (GRP) family from rats. Northern blot analysis revealed that SMARP mRNA is expressed, out of the major mouse organs, only in the SMG and exorbital lacrimal gland (LG), with much more abundance in the former. For the SMG, the level of SMARP mRNA was 36 times higher in females than males, whereas for the LG it was 28 times higher in males than females. Furthermore, the level of SMARP mRNA was increased in the SMG but reduced in the LG with castration in males, whereas it was reduced in SMG but increased in LG after administration of testosterone in females or castrated males. In situ hybridization detected the signal for SMARP mRNA in the female SMG, and immunohistochemistry detected the signal for SMARP protein in the female SMG and male LG. In the female SMG, SMARP mRNA, and protein were localized intensively in a subpopulation of acinar cells, whereas in the male LG, SMARP protein was distributed diffusely in all acinar cells. These results suggested that SMARP is a secretory protein whose expression is regulated by androgens negatively in the SMG and positively in the LG.


Subject(s)
Androgens/physiology , Lacrimal Apparatus/metabolism , Protein Sorting Signals/physiology , Salivary Proteins and Peptides/metabolism , Submandibular Gland/metabolism , Androgens/pharmacology , Animals , Down-Regulation , Female , Glutamic Acid/analysis , Glutamine/analysis , Lacrimal Apparatus/drug effects , Male , Mice , Mice, Inbred Strains , Orchiectomy , Ovariectomy , Proline/analysis , Protein Sorting Signals/drug effects , RNA, Messenger/analysis , Rats , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Sequence Homology, Amino Acid , Sex Characteristics , Submandibular Gland/drug effects , Testosterone/pharmacology , Up-Regulation
18.
Quintessence Int ; 37(8): 653-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16922026

ABSTRACT

OBJECTIVE: Salivary incubation assays are commonly used in oral malodor studies. Using an in vitro model system, the effect of various natural medicinals (i.e., echinacea, propolis, elder, mastic gum, marigold, sage, lavender, thyme, and chamomile) on salivary protein putrefaction and malodor production was examined. METHOD AND MATERIALS: Malodor production levels were scored by an experienced odor judge. Volatile sulfide levels were measured using a sulfide monitor (Halimeter), and salivary protein degradation was determined densitometrically following electrophoresis on polyacrylamide gel (SDS-PAGE). Microbial population was evaluated by viable counts and microscopy. RESULTS: Whereas all of the various medicinals caused some reduction in malodor production from the incubated whole saliva, echinacea and lavender were the most effective. CONCLUSION: The bioassay utilized in the present study suggests that these herbs may inhibit oral malodor production.


Subject(s)
Halitosis/drug therapy , Phytotherapy/methods , Plant Preparations/therapeutic use , Salivary Proteins and Peptides/drug effects , Adult , Analysis of Variance , Echinacea , Humans , Lavandula , Plants, Medicinal
19.
J Med Dent Sci ; 52(4): 183-8, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16669451

ABSTRACT

In this study, patients with heart diseases were classified into 2 groups: Warfarin user and Warfarin non-user, and six salivary components were determined to assess intraoral pathologic conditions. Groups of healthy subjects and patients with periodontal disease without receiving any medication were set as control groups, and they were compared with those of the 2 groups with heart diseases. In patients with heart diseases in both the groups, albumin (ALB) level was found to be significantly higher compared to that in the control groups, and it was significantly higher in the patient group receiving Warfarin user and Warfarin non-user compared to that in the patient group with periodontal disease. C-reactive protein (CRP) levels were found to be higher in both the groups with heart diseases than those in the healthy group. Correlations between various salivary components and the clinical parameters were examined, showing significant correlations between ALB and gingival index (GI) and clinical attachment level (CAL), and between alanine aminotransferase (ALT) and GI, probing depth (PlI), bleeding on probing (BOP) and CAL. Significant correlations were also found between creatine kinase (CK) and PlI, GI and BOP. Thus, it was suggested that ALB and CRP might serve as the markers of intraoral pathologic conditions, and CK and ALT might serve as those alternative to GI.


Subject(s)
Cardiovascular Agents/therapeutic use , Heart Diseases/drug therapy , Saliva/drug effects , Adult , Aged , Alanine Transaminase/analysis , Alanine Transaminase/drug effects , Albumins/analysis , Albumins/drug effects , Anticoagulants/therapeutic use , Aspartate Aminotransferases/analysis , Aspartate Aminotransferases/drug effects , Biomarkers/analysis , C-Reactive Protein/analysis , C-Reactive Protein/drug effects , Creatine Kinase/analysis , Creatine Kinase/drug effects , Dental Plaque Index , Gingival Hemorrhage/metabolism , Humans , Middle Aged , Periodontal Attachment Loss/metabolism , Periodontal Diseases/metabolism , Periodontal Index , Periodontal Pocket/metabolism , Saliva/chemistry , Salivary Proteins and Peptides/analysis , Salivary Proteins and Peptides/drug effects , Warfarin/therapeutic use
20.
Support Care Cancer ; 11(4): 207-25, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12673459

ABSTRACT

This review presents data from the literature on oral adverse reactions from the perspectives of subjective feelings of dry mouth (xerostomia) and objective measures of salivary gland hypofunction during and after cancer therapy. Special emphasis is paid to the mechanisms behind xerostomia, impaired saliva secretion and changes in the composition of saliva and to how these relate to radiation therapy involving the salivary glands and to systemic chemotherapy. The oral complications that relate to such iatrogenic changes in salivary gland function are also discussed.


Subject(s)
Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Neoplasms/radiotherapy , Radiotherapy/adverse effects , Xerostomia/etiology , Antineoplastic Agents/pharmacokinetics , Electrolytes/radiation effects , Humans , Mouth Diseases/etiology , Saliva/drug effects , Saliva/radiation effects , Salivary Glands/drug effects , Salivary Glands/physiology , Salivary Glands/radiation effects , Salivary Proteins and Peptides/drug effects , Salivary Proteins and Peptides/radiation effects , Time , Xerostomia/physiopathology , Xerostomia/prevention & control
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