Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na-K-2Cl cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca and Ca ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca entry, resulting in hyposalivation in mouse submandibular glands.
Acinar Cells ; drug effects ; metabolism ; Animals ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; Carbachol ; pharmacology ; Dexamethasone ; therapeutic use ; Mice ; Muscarinic Agonists ; pharmacology ; Saliva ; metabolism ; Salivation ; drug effects ; Submandibular Gland ; drug effects ; metabolism

OBJECTIVETo explore the molecular mechanism of exocrine immune inflammatory injury of Sjögren's Syndrome and the intervention of Banxia Qinlian Decoction (BQD).

METHODSTotally 18 female NOD mice were randomly divided into the model group, the positive drug group, and the BQD group, 6 in each group. Six female BALB/c mice were recruited as a blank control group. Mice in the blank control group and the model group were gavaged with deionized water at the daily dose of 0.1 mL/10 g body weight. Tripterygium Tablet was administered by gastrogavage to mice in the positive group at the daily dose of 10 mg/kg. BQD was administered by gastrogavage to mice in the BQD group at the daily dose of 60 g crude drugs/kg. After 12 weeks of medication, mice were sacrificed. Their eyeballs were excised and blood collected. Tissues of bilateral parotids and submandibular glands were kept. mRNA transcriptional levels of IL-17, IL-6, type 3 muscarinic acetylcholine receptors (M3R), aquaporin protein-5 (AQP5) were detected by RT-PCR. Expression levels of M3R and AQP5 protein were detected by Western blot. Protein expression levels of IL-17 and IL-6 were detected by ELISA.

RESULTSCompared with the normal group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly up-regulated in the model group (P < 0.01). Compared with the model group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly down-regulated in the positive drug group and the BQD group with statistical difference (P < 0.01, P < 0.05). Compared with the BQD group, mRNA-transcriptional levels of IL-17, IL-6, and M3R, as well as M3R and AQP5 protein expression levels were significantly down-regulated in the positive drug group (all P < 0.01).

CONCLUSIONThe molecular mechanism of BQD in inhibiting SS exocrine neurotoxic injury might be possibly related to regulating Th17/IL-17 immune inflammatory way.

Animals ; Aquaporin 5 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-17 ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Sjogren's Syndrome ; drug therapy ; immunology ; Submandibular Gland ; Th17 Cells ; Up-Regulation

OBJECTIVETo explore the mechanism of Astragalus polysaccharides (APS) for improving the cardiac function of Sjogren's syndrome (SS) model rats based on Keapl-Nrf2/ARE signaling pathway.

METHODSTotally 48 male Wistar rats were randomly divided into four groups by random digit table, i.e., the blank control group,the model control group,the APS group, and the hydroxychloroquine group, 12 in each group. Except those in the blank control group, 0. 1 mL mixed antigen protein of sufficiently emulsified Freund's complete adjuvant and submandibular gland protein was injected from two feet plantar to induce SS model. The intervention was started from 19th day after inflammation induction. Equal volume of normal saline was given to rats in the blank control group (1 mL/100 g), APS was administered to those in the APS group (1 mg/100 g), and hydroxychloroquine (0.03 125 g/kg) was administered to those in the hydroxychloroquine group. All rats were intervened once per day for 30 consecutive days. Changes of rats' body mass and drinking water quantity, submandibular gland index, spleen index, histological changes of glands were observed. Changes of the heart function were monitored using invasive hemodynamics. Serum reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-alpha), and interleukin-35 (IL-35)were detected using ELISA method. The pathological changes were observed using HE staining. The protein expression of ROS, reactive nitrogen species (RNS), glutathione (GSH), and thioredoxin (TRX) were observed by immunohistochemical staining. The mRNA expression of Keap1, Nrf2, and ARE was detected using real time fluorescent quantitative PCR. The protein expression levels of gamma-glutamic acid and a half long glycine synthetase (gamma-GCS) and heme oxygenase 1 (HO-1) in the myocardial tissue were determined by Western blot method. Results Compared with the blank control group, the quantity of drinking water, submandibular gland index, spleen index, heart rate (HR), cardiac index (HI), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap 1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly increased (P <0.01); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH, and TRX significantly decreased (P <0.01) in the model group. Compared with the model group, the quantity of drinking water, submandibular gland index, spleen index, LVEDP, MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly decreased (P<0.05); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH protein expression, and TRX protein expression significantly increased (P < 0.05, P <0.01) in the AR group and the hydroxychloroquine group. In the hydroxychloroquine group HR increased (P <0.05). In the AR group HR and LVSP decreased (P <0. 05, P <0. 01). Compared with the hydroxychloroquine group, HR, LVEDP, - dp/dtmax, y-GCS protein expression significantly decreased (P <0. 05, P <0. 01); SOD, TAC, GSH, TRX, HO-1 protein expression increased (P <0.01 )in the AR group. HI was positively correlated with ROS (P <0. 05). LVSP and LVEDP were positively correlated with Keap1 -Nrf2/ARE signaling pathways (P <0. 01) , and negatively correlated with TAC (P <0. 05, P <0. 01 ). +/-dp/dtmax was negatively correlated with Keap1-Nrf2/ARE signaling pathways(P <0.05), and positively correlated with TNF alpha (P <0. 05).

CONCLUSIONSDeclined heart function exists in SS rats. The mechamechanism of APS for improving the heart function might be closely correlated with activating Keap1-Nrf2/ARE signaling pathway.

Animals ; Astragalus Plant ; Blotting, Western ; Carboxylic Ester Hydrolases ; metabolism ; Heme Oxygenase-1 ; metabolism ; Hydroxychloroquine ; Male ; Malondialdehyde ; metabolism ; Myocardium ; enzymology ; NF-E2-Related Factor 2 ; metabolism ; Plant Extracts ; therapeutic use ; Polysaccharides ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Sjogren's Syndrome ; Submandibular Gland ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjogren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA.
Acidosis, Renal Tubular/*diagnosis/etiology ; Acute Disease ; Adult ; Antibodies, Antinuclear/blood ; Calcium Gluconate/therapeutic use ; Chronic Disease ; Female ; Humans ; Hydrogen-Ion Concentration ; Hypocalcemia/*chemically induced/complications/drug therapy ; Nephrocalcinosis/complications/*diagnosis/ultrasonography ; Parotid Gland/ultrasonography ; Phosphates/*adverse effects ; Salivary Glands/radionuclide imaging ; Sjogren's Syndrome/complications/*diagnosis/metabolism ; Submandibular Gland/ultrasonography

OBJECTIVETo observe effect of prescriptions replenishing vital essence, tonifying Qi and activating blood on expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-IP (IL-1beta) in serum and submaxillary gland of non-obese diabetic (NOD) mice with Sjogren's syndrome.

METHODThirty-two NOD mice were divided into four groups at random: the model group, the traditional Chinese medicine (TCM) group, the hydroxychloroquine group, the TCM and western medicine (WM) group, with 8 mice in each group. Eight Balb/C mice were taken as the normal normal control group. The TCM group was orally administered with 0.4 mL decoction replenishing vital essence, tonifying Qi and activating blood (100 g x kg(-1)) everyday; the hydroxychloroquine group were given 0.4 mL hydroxychloroquine (60 mg x kg(-1)) everyday; the TCM WM group were given 0.4 mL decoction, replenishing vital essence tonifying Qi and activating blood (50 g x kg(-1)) and hydroxychloroquine (60 mg x kg(-1)) everyday. Mice were sacrificed after eight weeks, and their arterial blood and tissues of submaxillary gland were collected. The levels of TNF-alpha, IL-1beta in serum were detected by ELISA. Expressions of TNF-alpha, IL-1beta protein in submaxillary gland were detected by immunohisto-chemistry.

RESULTCompared with other groups, TNF-alpha, IL-1beta in serum and submaxillary gland in the model group were higher (P < 0.05). The normal group showed lower serum TNF-alpha level than other groups (P < 0.05), but without statistical significance compared with the TCM group. IL-1beta in serum in the TCM group and the TCM WM group were lower than that of the hydroxychloroquine group (P < 0.05), but without statistical significance compared with the normal group. TNF-alpha protein expression in the TCM group and the TCM WM group showed no significant difference compared with the normal group, whereas the TCM WM group were notably lower than that of the hydroxychloroquine group (P < 0.05). IL-1beta expression in the TCM WM group showed no significant difference compared with the normal group.

CONCLUSIONThe decoction replenishing vital essence, tonifying Qi and activating blood can decrease the levels of TNF-alpha, IL-1beta in serum and submaxillary gland of NOD mice with Sjogren's syndrome. It may improve pathological damage of submaxillary gland by regulating Th1/Th2 cell factors, in order to achieve the therapeutic effect on SS.

Animals ; Antirheumatic Agents ; pharmacology ; Drug Administration Schedule ; Drug Therapy, Combination ; Enzyme-Linked Immunosorbent Assay ; Hydroxychloroquine ; pharmacology ; Immunohistochemistry ; Interleukin-1beta ; analysis ; blood ; Medicine, Chinese Traditional ; methods ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Random Allocation ; Sjogren's Syndrome ; blood ; drug therapy ; metabolism ; Submandibular Gland ; metabolism ; Tumor Necrosis Factor-alpha ; analysis ; blood

Carcinoma, Squamous Cell ; pathology ; Child ; Cysts ; pathology ; Diagnosis, Differential ; Epithelium ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Keratin-7 ; metabolism ; Keratins ; metabolism ; Neoplasm Recurrence, Local ; surgery ; Reoperation ; Submandibular Gland ; surgery ; Submandibular Gland Neoplasms ; metabolism ; pathology ; surgery ; Transcription Factors ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; metabolism

PURPOSE: Plasma neurotrophin-3 (NT-3) levels are associated with several neural disorders. We previously reported that neurotrophins were released from salivary glands following acute immobilization stress. While the salivary glands were the source of plasma neurotrophins in that situation, the association between the expression of neurotrophins and the salivary gland under chronic stress conditions is not well understood. In the present study, we investigated whether NT-3 levels in the salivary gland and plasma were influenced by chronic stress. MATERIALS AND METHODS: Expressions of NT-3 mRNA and protein were characterized, using real-time polymerase chain reactions, enzyme-linked immunosorbent assay, and immunohistochemistry, in the submandibular glands of male rats exposed to chronic stress (12 h daily for 22 days). RESULTS: Plasma NT-3 levels were significantly increased by chronic stress (p<0.05), and remained elevated in bilaterally sialoadenectomized rats under the same condition. Since chronic stress increases plasma NT-3 levels in the sialoadenectomized rat model, plasma NT-3 levels were not exclusively dependent on salivary glands. CONCLUSION: While the salivary gland was identified in our previous study as the source of plasma neurotrophins during acute stress, the exposure to long-term stress likely affects a variety of organs capable of releasing NT-3 into the bloodstream. In addition, the elevation of plasma NT-3 levels may play important roles in homeostasis under stress conditions.
Animals ; Male ; Neurotrophin 3/*blood/genetics ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological/*physiology ; Submandibular Gland/*metabolism

OBJECTIVETo investigate the clinical and laboratory characteristics of tumor like Sjögren's syndrome (TLSS) patients and non-tumor like Sjögren's syndrome (NTLSS) and the incidence of lymphoma in patients of Sjögren's syndrome (SS).

METHODSA retrospective analysis was carried out in 199 primary SS (including TLSS) patients who were recruited in Peking University School and Hospital of Stomatology from 1998 to 2010. Clinical and laboratory information were collected. The patients were divided into two groups: TLSS (n = 25) and NTLSS (n = 174). Clinical and laboratory characteristics were compared between these two groups by a statistical analysis.

RESULTSOf the 25 TLSS patients, 23 had enlargements of parotid glands and 2 had enlargements of submandibular glands. There were significant differences of salivary scintigraphy appearance (P = 0.018), hypergammaglobulinemia (P = 0.014), rheumatoid factor positive rate (P = 0.001), formation of the ectopic germinal centers (P = 0.014), double positive rate of anti-SSA antibody and anti-SSB antibody (P < 0.001) between the TLSS and NTLSS patients. Among the 25 TLSS patients, 3 developed lymphomas, accounting for 1.5% (3/199) of the total 199 patients and 12% (3/25) of the TLSS patients. Lymphoma subtypes included one diffused large B-cell lymphoma and two mucosa-associated lymphoid tissue lymphoma. There was no lymphoma detected in NTLSS patients.

CONCLUSIONSThere are clinical and laboratory differences between TLSS and NTLSS patients, with a more tendency to develop lymphomas in TLSS patients.

Adult ; Antibodies, Antinuclear ; metabolism ; Female ; Humans ; Hypergammaglobulinemia ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; diagnostic imaging ; etiology ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; diagnostic imaging ; etiology ; metabolism ; pathology ; Male ; Middle Aged ; Parotid Gland ; pathology ; Radionuclide Imaging ; Retrospective Studies ; Rheumatoid Factor ; metabolism ; Salivary Glands ; diagnostic imaging ; Sjogren's Syndrome ; complications ; diagnostic imaging ; metabolism ; pathology ; Submandibular Gland ; pathology

OBJECTIVETo analyze the clinicopathologic features of chronic sclerosing submaxillaritis (CSS).

METHODSThe clinical and pathological characteristics of 9 CSS were analyzed.

RESULTSIn the 9 patients, there were 6 males and 3 females. The age of patients ranged from 51 - 77 years old. All of the tumors were located in the submandibular gland, presenting with painless and firm mass. Histologically, a well-defined mass lesion with extensive lymphocytes and plasma cells infiltration, preservation of lobular architecture, with acinar atrophy. The reactive hyperplasia of lymphoid follicles may be found in CSS. The phlebitis and obliterating phlebitis also formed. Immunohistochemistry showed evidence of diffuse infiltration of plasma cells. The mean number of IgG4-positive plasma cell per high-power field (HPF) was 186, mean value of the IgG4:IgG ratio was 0.71. Three of these 9 cases had manifestations of IgG4-associated systemic disease.

CONCLUSIONSCSS is considered as a part of IgG4-related sclerosing diseases, recognition of which is very essential for a successful treatment. When diagnosis is made, it is necessary to ascertain whether lesion occurs within salivary gland only or in combination with outside IgG4-related sclerosing disease. The establishment of follow-up is also necessary. Some patients show good response to steroid therapy.

Aged ; Female ; Humans ; Immunoglobulin G ; metabolism ; Male ; Middle Aged ; Plasma Cells ; immunology ; Sclerosis ; Sialadenitis ; metabolism ; surgery ; Submandibular Gland ; pathology ; surgery

Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject.
Biopsy, Fine-Needle ; Diagnosis, Differential ; Facial Muscles/*immunology/pathology/radiography ; Follow-Up Studies ; Humans ; Immunoglobulin G/*immunology/metabolism ; Immunohistochemistry ; Lacrimal Apparatus/*immunology/metabolism/pathology ; Lacrimal Duct Obstruction/complications/diagnosis/*immunology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sclerosis ; Submandibular Gland/*immunology/pathology/radiography ; Submandibular Gland Diseases/complications/diagnosis/*immunology ; Tomography, X-Ray Computed