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[Ultrastructure of the submandibular glands in rats kept in weightlessness].

Submandibular salivary glands of male rats weighing 330-350 g were examined after space flight and ground-based control study. Light microscopy was carried out using hematoxylin-eosin staining and PAS-reaction. Electron microscopy was performed using glutaraldehyde and osmium tetroxide fixation and contrasting according to Reynolds. Light microscopy revealed no destructive changes in the gland parenchyma; differences between flight and control rats remained within physiological limits. Electron microscopy of acinar cells of flight animals showed chromatin condensation, darkening of cells and nuclei, appearance of electron-dense vacuoles, fragmentation fo the granular endoplasmatic reticulum as well as enlargement of interstitial spaces, lumens of acini and intercellular canaliculi, loosening of basal membranes, and thinning of capillary walls. Electron microscopy of acinar cells of control rats demonstrated chromatin condensation in nuclei and fragmentation of the GER. Thus, both animal groups exhibited ultrastructural signs of inhibition of the synthesis and excretion of salivary protein. In addition, flight animals showed increased excretion and, probably, secretion of water and electrolytes. Examinations of granulocytes revealed enlargement of secretory granules in both animal groups, the largest granules being seen in flight animals. They also showed mitochondrial swelling which was most significant in control rats. After the ground-based study cells of the striated compartment also displayed a very distinct mitochondrial swelling which may reduce the reabsorption capacity and enhance salivation of the compartment. However the mechanism of these changes seems to be different from that underlying changes after real space flight.

Animals↗
PubMed2002

Carcinoma of the parotid and submandibular glands--a study of survival in 2465 patients.

Salivary gland carcinomas demonstrate a wide diversity of histopathological types and biological behavior. The aim of this study was to analyze relative survival of patients with major salivary gland carcinomas with special reference to histopathology, gender and age. All new carcinomas of the major salivary glands reported to the National Swedish Cancer Registry 1960-1995 were searched for and the vital status of the cases was updated by record linkage to the Swedish Population Registry through December 31 1996. The study comprised 2465 patients with carcinoma of the parotid or submandibular glands. Relative survival differed markedly according to histopathological typing (P<0.001). For parotid tumors, acinic cell carcinomas had the best prognosis with a 10-year relative survival of 88%. The corresponding figures for mucoepidermoid carcinomas, adenoidcystic carcinomas and carcinoma ex pleomorphic adenoma were 80, 74 and 73%. Adenocarcinoma NOS and undifferentiated carcinoma had worse prognosis, with 10-year relative survival of 55 and 44%. Patients with submandibular gland cancer had similar relative survival to those with parotid cancers, besides those with mucoepidermoid cancer and adenocarcinoma NOS, who carried worse prognosis. Age and gender had an impact on relative survival for patients with mucoepidermoid carcinoma, adenocarcinoma and undifferentiated cancer of the parotid.

Adolescent↗
PubMed1976

Effect of isoproterenol on the kallikrein content of the submandibular gland of rats.

The influence of IPR on the kallikrein content of the submandibular gland of 11, 21, 62 and 90 day old rats was investigated. The appearance of acini in IPR treated rats was associated with an increase in the kallikrein content of the gland in 11 day old rats. The decrease of kallikrein in the gland of 21 to 90 day old animals was attributed to the maturation of the autonomic nervous system and the mechanism of glandular secretion.

Age Factors↗
PubMed1994

Radiation-induced cell proliferation in the parotid and submandibular glands of the rat.

Repopulation of tissues with cells at damaged sites is an important feature in the recovery of radiation-induced tissue injury. To obtain insight into the regenerative process in salivary gland tissue, proliferative activity was measured as a function of time in the different epithelial cell compartments of rat parotid and submandibular glands after local X irradiation with a single dose of 15 Gy. Bromodeoxyuridine-labeling indices were determined before and 10 h and 1, 3, 6, 10, 15, 20 and 30 days after irradiation. In both glands, X irradiation caused cell death and cell cycle delay manifested during the first day. Three days after irradiation, cell proliferation started in the intercalated duct. Six days after irradiation, proliferation was also observed in acinar and granular convoluted tubule cells. The striated ducts showed proliferative activity starting at day 6 (parotid) and day 10 (submandibular), respectively. The results of this study suggest that after 15 Gy of X rays repopulation takes place in all cell compartments. From the present study it cannot deduce if these cells are originating solely from progenitor cells residing in the intercalated duct or if cells of the other compartments are also stimulated. Proliferative activity was found to be higher in the intercalated duct compartment of the parotid gland than of the submandibular gland, which may be related to the suggested greater radiosensitivity and thus a greater demand for cell replenishment in the parotid gland.

Animals↗
PubMed1985

Stimulation of glucose oxidation in rat submandibular gland cells in vitro by analogues of cyclic AMP.

Secretion from salivary glands, following autonomic stimulation, is energy-dependent. Rat submandibular gland cells, when treated in vitro with both alpha- and beta-adrenergic agonists, showed increased glucose oxidation. The effects of alpha-adrenergic agents on glucose metabolism can be mimicked by non-receptor mobilization of Ca2+. Analogues of cyclic AMP were capable of elevating glucose metabolism to nearly the same extent as beta-adrenergic agonists.

Animals↗
PubMed1988

[Frequent occurrences of an enlarged submandibular gland following interstitial irradiation therapy in patients with cancer of the tongue].

A submandibular gland enlargement produces complications in the diagnosis of a nodal metastasis during the follow-up period in patients who have been given interstitial irradiation therapy for their oral cancers. Thus, a retrospective study has been made of the records of such affected patients, to accumulate knowledge regarding the frequency, the time of appearance, and the symptoms leading to the gland enlargement. Among 155 cases of squamous cell carcinoma of the tongue, 73 cases were selected for this study by the following criteria: (1) the patients were free of metastatic adenopathy, (2) they had been interstitially irradiated, and, (3) they were followed-up without surgical treatment for more than 6 months after the radiotherapy. Gland enlargement was found to have developed in 70% of the studied patients, that is, in 49 of the 73 cases within 9 months after radiotherapy.

Brachytherapy↗
PubMed1990

Expression and induction by beta-adrenergic agonists of the cystatin S gene in submandibular glands of developing rats.

Repeated administration of the beta-adrenergic agonist isoprenaline (isoproterenol, IPR), which produces hypertrophic/hyperplastic enlargements of rat submandibular and parotid glands, induces synthesis of a secretory protein shown to be a cysteine proteinase inhibitor, rat cystatin S. In the current study, Northern blot and hybridizations in situ were carried out to establish the developmental and beta-adrenergic regulation of the expression of the cystatin S gene. Cystatin S mRNA was not detected in submandibular glands of 20-day-old fetuses, nor in the glands of newborn or 10-day-old rats. However, steady-state levels of cystatin S mRNA increased between 21 and 28 days, reaching a conspicuously high concentration at 28 days; cystatin S mRNA then declined rapidly to a barely detectable level in glands of 32-day-old rats. IPR administration for 4 days induced high levels of cystatin S mRNA in submandibular glands of developing and adult rats. In both prepubertal and mature animals, induction of cystatin S mRNA in submandibular glands was more pronounced in female than in male animals. Hybridizations in situ revealed cystatin S mRNA only in acinar but not in duct cells of the submandibular gland. Developmentally, expression of the cystatin S gene coincided with acinar cell differentiation. These data suggest a complex neural, hormonal and developmental regulation of salivary cystatin genes.

Adrenergic beta-Agonists↗
PubMed1979

Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus.

Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.

Animals↗
PubMed1980

Congenital basal cell adenoma of the submandibular gland.

Basal cell adenoma is a specific type of monomorphic tumor of the salivary glands that closely resembles basal cell lesions of the skin. Twenty-six of these tumors have been reported in the American literature, the majority occurring in patients 60 years or older. The most common sites of occurrence have been the minor salivary glands (especially in the upper lip) and the parotid. We report an exceptional case of basal cell adenoma in the submandibular gland of a neonate. Review of reported congenital epithelial tumors of the salivary glands indicates that at least two similar neoplasms have been described previously.

Adenoma↗
PubMed1980

Inhibition of parasympathetic axonal sprouting in the cat submandibular gland by sympathetic axons. A histochemical study.

The sprouting of parasympathetic axons into the submandibular sympathetic nerve trunk following sympathetic denervation has been investigated. It was found that a permanent sympathetic denervation was necessary in order for the sprouting to devleop and be maintained: if reinnervation by adrenergic nerves was delayed, the sprouting developed but was reduced at longer survival times when the original innervation was reestablished. The evidence for suppression of the cholinergic sprouting by the adrenergic axons is discussed, as is the evidence that these sprouts arise from the submandibular gland.

Animals↗
PubMed1999

ATP-dependent activation of K(Ca) and ROMK-type K(ATP) channels in human submandibular gland ductal cells.

[Ca(2+)](i) and membrane current were measured in human submandibular gland ductal (HSG) cells to determine the regulation of salivary cell function by ATP. 1-10 microM ATP activated internal Ca(2+) release, outward Ca(2+)-dependent K(+) channel (K(Ca)), and inward store-operated Ca(2+) current (I(SOC)). The subsequent addition of 100 microM ATP activated an inwardly rectifying K(+) current, without increasing [Ca(2+)](i). The K(+) current was also stimulated by ATP in cells treated with thapsigargin in a Ca(2+)-free medium and was blocked by glibenclamide and tolbutamide, but not by charybdotoxin. This suggests the involvement of a Ca(2+)-independent, sulfonylurea-sensitive K(+) channel (K(ATP)). UTP mimicked the low [ATP] effects, while benzoyl-ATP activated internal Ca(2+) release, a Ca(2+) influx pathway, and K(Ca). Thus, ATP acts via P(2U) (P2Y(2)) and P(2Z) (P2X(7)) receptors to increase [Ca(2+)](i) and activate K(Ca), but not K(ATP). Importantly, (i) ROMK1 and the cystic fibrosis transmembrane regulator protein (but not SUR1, SUR2A, or SUR2B) and (ii) cAMP-stimulated Cl(-) and K(+) currents were detected in HSG cells. These data demonstrate for the first time that a ROMK-type K(ATP) channel is present in salivary gland duct cells that is regulated by extracellular ATP and possibly by the cystic fibrosis transmembrane regulator. This reveals a potentially novel mechanism for K(+) secretion in these cells.

Adenosine Triphosphate↗
PubMed1984

Intrauterine proximity to male fetuses predetermines level of epidermal growth factor in submandibular glands of adult female mice.

Morphological, behavioral, and physiological masculinization of adult female mice that developed in utero between two male fetuses (2M females) has been previously attributed to the significantly higher concentration of testosterone in their fetal blood and amniotic fluid than that in female mice which had not been contiguous to males in utero (0M females). Serum testosterone levels of adult 2M and 0M females are not significantly different. To determine whether exposure of fetuses to different levels of testosterone during prenatal development alters adult biochemical parameters of a system responsive to testosterone, the level of epidermal growth factor (EGF) was measured by radioreceptor assay in the submandibular glands of adult CF-1 mice of known intrauterine position. The concentration of EGF was significantly higher (P less than 0.05) in the glands of 2M females (mean +/- SEM, 0.36 +/- 0.14 nmol/mg dry wt of tissue; n = 6) than that in 0M females (0.05 +/- 0.00 nmol/mg dry wt; n = 8). In contrast, EGF concentration did not differ significantly between the glands of 2M and 0M males (0.51 +/- 0.01 and 1.10 +/- 0.42 nmol/mg dry wt, respectively). EGF levels were also determined in the submandibular glands from adult animals of unknown intrauterine position which were gonadectomized and then treated with testosterone and estradiol. The concentrations of EGF in the glands of gonadectomized males and females were similar (0.13 +/- 0.01 and 0.23 +/- 0.09 nmol/mg dry wt, respectively). However, there was a significant difference in response to hormonal administration between males and females. The response of females exceeded that of males at 400 and 800 micrograms testosterone/day. These results suggest that the hormonal environment of a fetus, specifically modification of the fetal environment by the production of hormones from adjacent fetuses, is a major factor in the adult expression of testosterone-responsive proteins such as EGF.

Amniotic Fluid↗
PubMed1995

Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat.

Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to determine the possible selectivity of glycopyrronium for M2 and M3 muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates were characterized with [3H]-N-methylscopolamine ([3H]-NMS) by ligand binding studies. Inhibition of [3H]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine >> otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine >> HHSiD >> pirenzepine > otenzepad. These were similar to the expected order of frequency of M2 and M3 subtypes, respectively. Glycopyrronium showed similarly high affinities for both M2 (Ki = 1.889 (SEM 0.049) nmol litre-1) and M3 (Ki = 1.686 (0.184) nmol litre-1) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M2 or M3 muscarinic receptor subtypes.

Animals↗
PubMed1983

Detection of renin mRNA in mouse kidney and submandibular gland by hybridization with renin cDNA.

The presence of renin mRNA in a tissue is a manifestation of the expression of the renin gene by that tissue. In the present study 32P-labeled, single-stranded renin complementary DNA was used as a specific probe for the detection of renin mRNA in tissues by hybridization of their complementary base sequences. With use of the technique of hybridization histochemistry, renin cDNA probe bound strongly to sections of submandibular gland from male Quackenbush mice, a tissue which displays high androgen-dependent renin synthesis. Less was present in the female gland. In the kidney the probe localized in the cortex. A dot hybridization assay was developed to measure renin mRNA in serially diluted total RNA spotted onto nitrocellulose filters along with renin cDNA standards. From the concentration the ratio of renin mRNA between male and female submandibular gland and kidney was calculated as approx. 100:8:1:1, respectively, which is similar to the relative proportion of renin concentrations between these tissues. The present study thus provides the basis for investigations of the expression of the renin gene by tissues, particularly those with high renin biosynthetic activity.

Animals↗
PubMed1999

Expression of manganese superoxide dismutase in rat submandibular gland demonstrated by in situ hybridization and immunohistochemistry.

Superoxide, an active oxygen species, plays an important role in protecting against bacterial infection. However, it also has adverse effects on health. Manganese superoxide dismutase (Mn-SOD) is a scavenger of superoxide. Antioxygen enzymes such as Mn-SOD exist in various tissues, and provide protections against oxidative injury. We investigated both the expression of Mn-SOD mRNA and the localization of Mn-SOD in adult rat submandibular glands using in situ hybridization and immunohistochemistry. Both Mn-SOD mRNA and Mn-SOD were detected in striated duct cells, and in some granular duct cells and excretory duct cells. With immunoelectron microscopy, many immunolabelings were observed on the mitochondria. These findings suggest that the expression of Mn-SOD mRNA and the localization of Mn-SOD in submandibular glands correlate with the number of mitochondria in cells.

Animals↗
PubMed2003

Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland.

The expression and localization of aquaporins (AQP1-AQP5), members of the water channel family, in the developing rat submandibular gland were analysed using RT-PCR, Northern blotting and immunohistochemistry to explore their relation to the development of this salivary gland. RT-PCR analysis revealed unique expression patterns of each AQP. AQP1 was expressed constitutively during prenatal development, whereas the expression of AQP5 became more intense in the course of development from embryonic day 16.5 (E16) to E20. These expression patterns concurred with the results of Northern blot analysis. AQP3 and AQP4 mRNAs in the prenatal development were not detected in Northern blots, although they were detected by RT-PCR. During postnatal development, AQP5 and AQP1 mRNAs were expressed continuously, but no message for AQP3 or AQP4 was detected. AQP2 mRNA was not detected during either prenatal or postnatal development in this tissue. Immunohistochemical studies revealed that AQP5 was first localized at the apical membrane of proacinar cells at E18, and then became clearly distributed at the apical membrane of acinar cells in accordance with the differentiation and establishment of the mature acini. In addition, some vasculature also showed immunoreactivity for AQP5. AQP1 was immunolocalized in the blood vessels, including capillaries, of the gland throughout development. These observations suggest the existence of transcriptional regulation of rat AQP5, which is one of the most probable regulators of saliva production and secretion, during the establishment of the functional submandibular salivary gland.

Aging↗