糖尿病大鼠下颌下腺内水通道蛋白-3和-8的表达变化及意义

目的观察水通道蛋白-3(AQP3)和水通道蛋白-8(AQP8)在糖尿病大鼠下颌下腺内表达变化。方法 SD大鼠随机分为对照组、糖尿病组和治疗组,每组10只;糖尿病组和治疗组大鼠腹腔注射2%链尿佐菌素(35 mg/kg)复制Ⅱ型糖尿病模型,治疗组予以胰岛素(3u/d)处理;8周后,取下颌下腺,分别进行HE和免疫组织化学染色。结果与对照组比较,糖尿病组下颌下腺腺泡轻度萎缩,细胞排列紊乱,导管数目减少,直径变小。AQP3表达在三组间无明显差异;与对照组比较,糖尿病组AQP8表达下降,治疗组AQP8表达较糖尿病组有所上调。结论糖尿病大鼠下颌下腺内AQP8低表达可能与糖尿病患者口渴的发病机制相关。     

Ultrastructural observations on luminal structures of pleomorphic adenoma of parotid and submandibular salivary glands of man

Summary Luminal structures found in salivary pleomorphic adenomas consisted of lumina surrounded by epithelial cells that varied from being packed together to being widely separated except at the luminal margin. Communication between lumina and the surrounding stroma was occasionally seen. Secretory material and cellular debris were seen in lumina, invaginations of the luminal surfaces of periluminal cells, associated vesicles, and vacuoles. Secretory granules, lysosomes and lipofuscin were seen in periluminal cells. Secretory material and debris from necrotic periluminal cells appear to accumulate in lumina, and to be endocytosed and degraded lysosomally by periluminal cells. The finding of communications between lumina and the surrounding stroma suggests that the stromalization of the epithelium includes the luminal structures. The present investigation supports the hypothesis that many of the cellular features of the pleomorphic adenoma relate to the microenvironment.     

Morphological changes in collagen fiber during development of human fetal parotid and submandibular glands

Parotid and submandibular glands from human fetuses (16, 20, 24, 28, 32 weeks of gestation) were examined under a scanning electron microscope. Changes were found in the arrangement of collagen fibers in the connective tissue surrounding the salivary gland. In particular, several layers around the salivary gland were formed by a collagen network structure. These structures, although in varied arrangements, were recognizable in each stage of fetal growth. They are thought to play the role of a "cushion" against pressure created by accumulation of granules because of the reflex activity of myoepithelial cells during secretion. These structural changes are related to the mechanical performance of granule formation in the salivary gland and secretion during the development of the fetus.     

Long‐term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands

Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long‐term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long‐term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland‐specific response to GCs. Our data emphasize that GC‐based therapies and insulin‐resistant states have a negative impact on salivary gland homeostasis.     

Histochemical and biochemical determination of calcium in salivary glands with particular reference to chronic submandibular sialadenitis

Although salivary calcification is relatively common, little is known about the localization and content of the calcium of normal and diseased human salivary glands. We investigated this in chronic submandibular sialadenitis with a variable mixture of relatively normal and extremely atrophic parenchyma and in normal submandibular, parotid and palatal glands. Calcium was localized histochemically in mucous acinar cells of submandibular and palatal glands at moderate to high levels, in serous acinar cells of submandibular and parotid glands at low to moderate or occasionally high levels, in mucous ductal cells at moderate to high levels, and in extremely atrophic parenchyma at low levels or not at all. Calcium was determined biochemically at relatively high levels in the different glands in the order palatal, submandibular, sialadenitis and parotid. However, the differences were small. The results indicate that most salivary calcium is associated with secretory granules; this is the likely source of the calcium involved in salivary calcification     

Nerve cell bodies and small ganglia in the connective tissue stroma of human submandibular glands

The objective of the study was to investigate the presence and distribution of nerve cell bodies and small ganglia in the stroma of human submandibular gland. A retrospective immunohistochemical study in 13 human submandibular glands, fixed in neutral buffered formalin and embedded in paraffin wax, was undertaken. Six glands were excised in the course of radical neck dissection for oral squamous cell carcinoma and were disease-free, six showed sialadenitis, and one was involved by tuberculosis. Primary antibodies applied were neuron specific enolase, synaptophysin, and glial fibrilliary acidic protein. Neuron specific enolase and synaptophysin positive nerve cell bodies and small ganglia were found in 8/13 and 13/13 glands, respectively. They were found in the interlobular connective tissue stroma of human SMG, in close association to salivary parenchymal cells and blood vessels, and some of them were incorporated in GFAP positive peripheral nerves. To our knowledge, nerve cell bodies and small ganglia have been described only in the connective tissue stroma of autotransplanted human SMG and their functional importance is not clear.     

Mucous droplets with multiple membranes in the accessory submandibular glands of long-winged bats

Background: Certain species of bats possess two sets of submandibular glands, namely, principal and accessory. The ultrastructure and histochemistry of the accessory submandibular gland was examined in three species of long-winged bats. Methods: Specimens of Miniopterus schreibersi and M. Magnator were live-trapped in Thailand, and of M. inflatus were live-trapped in Kenya. For electron microscopy, accessory submandibular lands were initially fixed in triple aldehyde-DMSO, postfixed in osmium tetroxide, and embedded in Epon-Maraglas. A portion of the glands collected in Thailand (M. schreibersi and magnator) was fixed in buffered formalin and embedded in paraffin. Sections of the latter material were subjected to a battery of histochemical tests for glycoconjugates. Results: Although in all three species the accessory submandibular glands have normal histological structure, the glands in two, M. schreibersi and M. magnator, were distinguished by possessing mucous droplets of unusual morphology. These droplets, whose identity as mucous was confirmed by histochemical tests for glygoconjugates, are delimited by maniflod membranes: up to 10 in M. Schreibersi and fewer, but still multiple, in M. magnator. In both species, the entire array of surface membranes may fold inward in the fashion of mitochondiral cristae, forming packets of membranes, many of which have the spurious appearance of floating free in the droplet matirix. These multipartite limiting membranes appear to originate simply by Golgi saccules and moderately large, flattened Golgi vesicles repeatedly wrapping themselves around the surface of nascent mucous droplets. During exocytosis, the outermost membrane of each mucous droplet contacts the luminal membrane, this barrie ruptures, then the remainder of the droplet—multiple membranes and matrix—either flow into the lumen or are cast out in toto. In either case, a great deal of membrane phospholipid is added to the salivea. This salivary lipid may permit these bats to consume insects that normally are able to repel predators with chemical defenses that make them unpalatable. The thrid species that we studied, M. inflatus, has mucous droplets of normal appearance, i.e., they have only one limiting membrane. Conclusions: The varying structure of mucous secretory products among the species of Miniopterus provides important clues as to the evolution of this genus as well as to the evolution of secretory cells in general. © 1994 Wiley-Liss, Inc.     

Evaluating the effect of three newly approved overactive bladder syndrome treating agents on parotid and submandibular salivary glands: Modulation of CXCL10 expression

Background

Despite enormous progresses in understanding pathophysiology of the lower urinary tract, antimuscarinics remain the chief clinically well-established approach for improving symptoms of overactive bladder (OAB). Dry mouth on the other hand remains one of the most untolerated systemic side effects of these drugs that limits their uses and results in high discontinuation rate. Three novel drugs have been recently approved by US Food and Drug Administration for treatment of OAB: trospium, darifenacin, and solifenacin.

Proliferative activity by cell type in the developing rat parotid gland

Background: In contrast to the considerable amount of research that has been done on the proliferative activity of the several types of parenchymal cells in the developing submandibular glands of rodents, systematic studies of cellular proliferation in the developing parotid gland have been confined to the acinar cells. The purpose of the present study was to attempt to fill this knowledge gap. Methods: Tritiated thymidine was parenterally administered to Sprague-Dawley rats at ages representative of the pre- and postnatal development of the parotid gland, and glands were harvested for autoradiography 90 min after injection. Mitotic activity among all cell types was verified by electron microscopy. Results: At all ages, the % labeled cells was much greater among the acini than any other cell type, including well-differentiated cells at 25 and 40 days. However, there were only small alterations in the proportions of cells comprised by the major cell types. Conclusions: Current theories on the histogenesis of salivary glands and their neoplasms are based on the renewing population model, in which both normal differentiated cells and neoplastic cells arise from undifferentiated stem cells in the ducts. However, these results suggest that most of the migration and redifferentiation in the developing rat parotid gland must be in the opposite direction, i.e., the acinar cells redifferentiate into ductal cells. They also indicate that until there are precise data on the rates of cell death among the several cell types, it remains more appropriate for salivary glands to be categorized as an expanding, rather than renewing, population. © 1995 Wiley-Liss, Inc.     

Chronology of peroxidase activity in the developing rat parotid gland

The course of development of salivary peroxidase, an enzyme that has an important role in oral defense mechanisms, has been well documented in rat submandibular glands. However, the only report on salivary peroxidase activity in the other major salivary glands of the rat has been a cytochemical study of the adult parotid gland. In the present investigation, the accumulation of salivary peroxidase activity in developing parotid glands of rats was followed both biochemically and cytochemically. Specific activity (units per mg protein) attributable to salivary peroxidase began at 1 day after birth, then rose rapidly but unevenly, with peaks at 21 and 70 days, and no difference between the sexes at any age. Activity per gland increased progressively to 42 days in both sexes and was significantly higher in males at 70 days. The cytochemical observations on peroxidase activity localized to the rough endoplasmic reticulum and secretory granules of the developing acini were well correlated with the biochemical findings. Peroxidase-negative cells occurred in immature acini at 1 and 7 days, but only in the intercalated ducts thereafter. This observation suggests that the acini are a source of some of the ductal cells, at least during early postnatal development. The developmental pattern of specific activity differed from those of other rat parotid secretory enzymes, indicating that control of their synthesis during development is noncoordinate. The patterns of specific activity of the parotid and submandibular glands were complementary, suggesting that their combined secretions may supply biologically significant peroxidase activity to the oral cavities of rats throughout postnatal development. © 1993 Wiley-Liss, Inc.     

糖尿病大鼠下颌下腺内水通道蛋白-1和5表达变化及意义

目的:观察水通道蛋白-1(AQP1)和水通道蛋白-5(AQP5)在糖尿病大鼠下颌下腺内表达变化,探讨糖尿病患者口渴症状的发生机制.方法:SD大鼠随机分为对照组、糖尿病组、治疗组.取大鼠下颌下腺,分别进行H-E染色、免疫组织化学显色(SP法)和计算机图像分析.结果:对照组和治疗组的血糖分别与糖尿病组血糖比较,均有差异;与...     

Morphological and functional changes of the rat parotid glandular cells by clipping and reopening the parotid duct, using ham8 antibody

The purpose of this experiment is to examine the proliferative process of rat acinar cells after parotid duct ligation and reopening. Two experimental groups were observed. The first group was killed from 0 to 14 days after the duct ligation. In the second group, the duct was clipped for 14 days, and it was reopened. Following a period of from 2 to 28 days after removal of the clip, the glands were removed to perform a histological analysis, including hematoxylin-eosin (HE), immunofluorescent staining using HAM8 antibody, which recognizes connexin 32, and transmission electron microscopy (TEM). In the experimental gland from the 1st group at 6 days after ligation (I-6D), the acinar cells disappeared. In the tissue from the 2nd group 8 days after reopening (II-8D), newly formed acinar cells were found again. Lobular structure of the parotid glands recovered in the II-21D. HAM8 signals were observed between normal acinar cells, while they declined in the tissue from I-1D, and they were not observed in the I-2D. HAM8 signals were first observed in the II-25D and then subsequently returned to normal levels in the II-28D. These results suggest that the intercellular communication and functional recovery was not complete 25 days after reopening of the duct.In conclusion, the recovery of the acinar structure was recognized during an extended period of duct ligation, however, a time lag between the morphological and functional recovery was found to exist.     

Intermediate filament expression in normal parotid glands and pleomorphic adenomas

Summary A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/ basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.     

Developmental changes of sugar occurrence and distribution in the rat submandibular and sublingual glands

 The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products. Accepted: 31 July 1998     

Loss of myoepithelium is variable in solid papillary carcinoma of the breast

AIMS: Reports on the frequency of myoepithelial loss in solid papillary carcinoma (SPC) of the breast, an unusual variant of papillary carcinoma with a solid pattern of expansile growth, have been strikingly contradictory. The aim was to clarify the frequency of myoepithelial loss in cases of SPC diagnosed at our institution. METHODS AND RESULTS: Eleven cases of SPC with available blocks or unstained slides were retrieved from the M. D. Anderson archives or obtained from outside contributors. Immunohistochemistry for smooth muscle actin (SMA) and p63 was evaluated on the circumscribed nests that appeared to be non-invasive by haematoxylin and eosin morphology. Three of the 11 cases (27%) were positive for both SMA and p63 at the periphery of all such foci, whereas eight cases (73%) lacked staining for both myoepithelial markers in at least one focus. Of these eight cases, one was diagnosed with only microinvasion, yet metastatic tumour resembling the circumscribed primary SPC was identified in two ipsilateral axillary lymph nodes. CONCLUSIONS: SPC of the breast frequently lacks myoepithelial markers at the tumour-stromal interface in spite of a circumscribed non-invasive appearance. Metastases from such tumours are infrequent, but can occur in cases that lack myoepithelial marker expression by immunohistochemistry.     

Sebaceous carcinoma of the parotid gland

Summary Sebaceous carcinoma of salivary gland origin is extremely rare and, because of its rarity, the clinicopathological characteristics and the histogenesis are not fully understood. We present a case of sebaceous carcinoma of the parotid gland which brings the total number of reported cases to 22.The tumor showed epithelial cell nests which were mainly composed of sebaceous cells with marked cellular atypia. In most of the nests, glandular spaces lined by ductal epithelium were present. Scattered mucous cells and flattened eosinophilic cells at the periphery of the nests were also seen. Ultrastructural and immunohistochemical observations of the tumour revealed coexistence of sebaceous and glandular differentiations in some tumour cells. Tumour cells with lipid granules often participated in the formation of glandular structures or exhibited intracytoplasmic lumina, and immunohistochemical localization of lactoferrin and secretory component, the functional markers of ductal epithelium of salivary gland, was demonstrated not only in duct-forming tumour cells but also in many sebaceous tumour cells.It seems likely that sebaceous carcinoma originates from pluripotential duct cells which can differentiate into sebaceous, ductal and mucous cells.     

Defensins in saliva and the salivary glands

Saliva contains several types of antimicrobial peptides that play a role in innate immunity. Peptides that were recently added to this list are the defensins. The purpose of this review is to summarize what is known about the production and role of defensins in the salivary glands and to discuss their therapeutic potential. The -defensins, human neutrophil defensins (HNP)-1, -2, and -3, have been detected in saliva and may be derived from neutrophils. The -defensins, human -defensins (HBD)-1 and -2, have also been detected in saliva. Although it has been speculated that salivary HBDs are derived from keratinocytes that line the oral mucosa rather than from the salivary glands, the HBD-1 peptide was recently found to be specifically expressed in salivary ductal cells, although not in acini. Defensins may be useful for the treatment of periodontal disease and for the prevention of caries and periodontitis.     

Perineurioma of the parotid gland: first case report

SUMMARY: Neurogenic neoplasms account for approximately 1% of salivary gland tumors. A 45-year-old woman presented with a slowly growing unilateral parotid gland mass that was excised completely by lateral parotidectomy. No recurrence was detectable 6 months after surgery. The resection specimen contained a 1.7 × 1.2 × 1-cm whitish nodular lesion that was firm, well circumscribed, and completely surrounded by compressed normal glandular tissue. The tumor was composed of spindle cells with bipolar tapering, wavy nuclei, and palely stained cytoplasm. The tumor cells were arranged in storiform, lamellar, and whorled patterns. Nuclear atypia, necrosis, and significant mitotic activity were absent. Immunohistochemistry showed expression of epithelial membrane antigen, glucose transporter 1, claudin-1, and collagen IV. All other lineage-specific markers including protein S100 were negative in the tumor cells. To our knowledge, this case represents the first report of soft tissue perineurioma in the salivary gland. Lack of previous reports suggests underrecognition of this tumor entity at this unusual anatomical site.     

The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

OBJECTIVES:

To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands.

INTRODUCTION:

Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants.

METHODS:

Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30) or 60 days (group C60) or pilocarpine for 60 days (group Pilo). The experimental groups were administered fluoxetine (group F30) or venlafaxine for 30 days (group V30); fluoxetine (group FS60) or venlafaxine (group VS60) with saline for 60 days; or fluoxetine (group FP60) or venlafaxine (group VP60) with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA), Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05).

RESULTS:

Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60) induced a significant decrease in the number of positively stained cells for calponin compared with all other groups.

CONCLUSIONS:

The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.