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Gland Dysfunction (gland + dysfunction)
Kinds of Gland Dysfunction Selected AbstractsDisruption of tight junction structure in salivary glands from Sjögren's syndrome patients is linked to proinflammatory cytokine exposureARTHRITIS & RHEUMATISM, Issue 5 2010Patricia Ewert Objective Disorganization of acinar cell apical microvilli and the presence of stromal collagen in the acinar lumen suggest that the labial salivary gland (LSG) barrier function is impaired in patients with Sjögren's syndrome. Tight junctions define cell polarity and regulate the paracellular flow of ions and water, crucial functions of acinar cells. This study was undertaken to evaluate the expression and localization of tight junction proteins in LSGs from patients with SS and to determine in vitro the effects of tumor necrosis factor , (TNF,) and interferon-, (IFN,) on tight junction integrity of isolated acini from control subjects. Methods Twenty-two patients and 15 controls were studied. The messenger RNA and protein levels of tight junction components (claudin-1, claudin-3, claudin-4, occludin, and ZO-1) were determined by semiquantitative reverse transcriptase,polymerase chain reaction and Western blotting. Tight junction protein localization was determined by immunohistochemistry. Tight junction ultrastructure was examined by transmission electron microscopy. Isolated acini from control subjects were treated with TNF, and IFN,. Results Significant differences in tight junction protein levels were detected in patients with SS. ZO-1 and occludin were strongly down-regulated, while claudin-1 and claudin-4 were overexpressed. Tight junction proteins localized exclusively to apical domains in acini and ducts of LSGs from controls. In SS patients, the ZO-1 and occludin the apical domain presence of decreased, while claudin-3 and claudin-4 was redistributed to the basolateral plasma membrane. Exposure of isolated control acini to TNF, and IFN, reproduced these alterations in vitro. Ultrastructural analysis associated tight junction disorganization with the presence of endocytic vesicles containing electron-dense material that may represent tight junction components. Conclusion Our findings indicate that local cytokine production in LSGs from SS patients may contribute to the secretory gland dysfunction observed in SS patients by altering tight junction integrity of epithelial cells, thereby decreasing the quality and quantity of saliva. [source] Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren's syndromeARTHRITIS & RHEUMATISM, Issue 12 2009Jelle L. Vosters Objective Interleukin-12 (IL-12) is a pleiotropic cytokine that is elevated in the affected organs of patients with Sjögren's syndrome (SS). We have previously reported that overexpression of IL-12 in CBA mice leads to mononuclear infiltration of salivary and lacrimal glands, as well as to expansion of bronchial lymphoid tissue and decreased mucociliary clearance. Because xerostomia is one of the most important clinical features in SS patients, our main objective in the current study was to evaluate salivary gland function in IL-12,transgenic mice. Our secondary objective was to further characterize this animal model and to determine if the changes observed in these mice are representative of those observed in patients with SS overall. Methods Pilocarpine-stimulated salivary flow was used to address salivary gland function in a large group of IL-12,transgenic mice bred onto the autoimmune-prone SJL background. Furthermore, salivary glands were removed to assess the formation of infiltrates in the glands and gland morphology. Serum was also collected from these animals to investigate the formation of autoantibodies. Results Pilocarpine-stimulated salivary flow was significantly lower in IL-12,transgenic mice than in wild-type controls. Salivary glands from transgenic mice exhibited an increase in both the number and the size of lymphocytic foci, versus glands from age-matched controls. Furthermore, the acini in transgenic mice were fewer in number and larger in size compared with acini in controls. An age-dependent increase in anti-SSB/La antibodies was observed in IL-12,transgenic mice and was accompanied by an increase in antinuclear antibodies. Conclusion Our findings indicate that a number of conditions associated with SS are exhibited by IL-12,transgenic SJL mice and that this model might be useful in researching multiple aspects of the disease. [source] Inflammatory stimuli accelerate Sjögren's syndrome,like disease in (NZB × NZW)F1 miceARTHRITIS & RHEUMATISM, Issue 5 2008Umesh S. Deshmukh Objective This study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice. Methods Female (NZB × NZW)F1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine-induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland,infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60. Results While IFA-treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS-treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA-treated mice showed significantly higher frequencies of CD11clow, B220+, Ly6C+, mouse PDCA-1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA-treated mice had higher levels. The gland dysfunction observed in IFA-treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland. Conclusion Our data suggest that generalized inflammatory stimuli can accelerate the development of SS-like disease in (NZB × NZW)F1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response. [source] 3446: Management and therapy of MGDACTA OPHTHALMOLOGICA, Issue 2010JM BENITEZ-DEL-CASTILLO Purpose Treatment of Meibomian gland dysfunction varies greatly among eye care providers.Practitioners have noted widespread deficiencies in the patient education. As a result, suboptimal and ineffective therapy is commonly practiced and abandoned prematurely as ineffective. The aim of the subcommittee was to review the current practice and published evidence of medical and surgical treatment options for Meibomian gland dysfunction and to identify areas with conflicting or lack of evidence, observations, concepts or even mechanisms were further research is required. Methods To achieve this a comprehensive review of clinical textbooks and scientific literature was performed and the quality of published evidence graded according to an agreed standard, using objective criteria for clinical and basic research studies. Results Lid warming and cleansing, artificial lubricants, systemic tetracyclines, topical antibiotic and or antibiotic-steroid combinations are commonly prescibed. Future developments are described. Conclusion The subcommittee have prsented current and future treatment options for Meibomian gland dysfunction. [source] 2433: A revolutionary hypothesis to explain Marx's line and progressive disease at the lid marginACTA OPHTHALMOLOGICA, Issue 2010AJ BRON Purpose The conjunctiva of the lid margin is protected from direct exposure to the atmosphere, by the tear meniscus. We examine the pathophysiological consequences of evaporation from this compartment. Methods A consideration of empirical data. Results The concave meniscus thins progressively to the point where it is pinned at the mucocutaneous junction (MCJ). We predict that, as a result, over the interblink period, evaporation generates a solute gradient which peaks behind the MCJ and is amplified over multiple cycles of the blink. We hypothesise that this creates a hyperosmolar state here which: i. stresses epithelial cells behind the MCJ, ii. stimulates a high cell turnover and iii. leads to immaturity of the surface cells and their glycocalyx. This is considered to explain an increased permeability to dyes at this site (rose bengal, lissamine green and fluorescein) and the stainability with dyes which is termed Marx's line. This gradient mechanism could also concentrate proteins, such as inflammatory mediators, at this location. Conclusion Since Marx's line lies directly behind the terminal Meibomian ducts and acini, chronic stress in this region is further invoked to explain forward migration of Marx's line and the MCJ which occurs with age and the induction of primary Meibomian gland dysfunction. Arguments are put forward to explain how this mechanism might be accentuated in dry eye and how the globe might be protected from this gradient effect in the region of the ,black line', where the tear film is segregated from the meniscus after the blink. Factors pro and con the hypothesis are discussed. [source] 2435: Control of the Meibomian gland in health and diseaseACTA OPHTHALMOLOGICA, Issue 2010DA SULLIVAN Purpose The meibomian gland is extremely important in maintaining the health and integrity of the ocular surface. This gland, through its lipid synthesis and secretion, promotes the stability and prevents the evaporation of the tear film. Conversely, meibomian gland dysfunction (MGD) leads to a decreased stability and increased evaporation of the tear film. Indeed, meibomian gland dysfunction is thought to be the major cause of dry eye syndromes throughout the world. Our goal is to advance understanding of the regulation of meibomian gland function and the mechanisms underlying MGD. Methods Procedures included the immortalization of human meibomian gland epithelial cells with human telomerase reverse transcriptase, the evaluation of cellular responsiveness, and the identification of glandular gene expression changes in MGD. Gene analyses were conducted with Illumina HumanHT-12 v3 Expression BeadChips and Geospiza bioinformatics software. Results To date we have [a] immortalized human meibomian gland epithelial cells that respond to secretagogue, growth factor, neurotransmitter and hormone exposure with alterations in proliferation, differentiation, signaling, gene expression and/or lipogenesis; [b] discovered human meibomian gland genes that may facilitate the development and/or progression of MGD. These genes encode proteins that promote keratinization and amplify inflammation. Conclusion Our findings advance our understanding of the control of the meibomian gland in both health and disease. [Acknowledgments: S.M. Richards, M. Hatton, A.M. Fay and K. Lo; Supported by grants from NIH (R01EY05612) and Alcon] Commercial interest [source] 2436: A critical look at meibometry as a means to monitor Meibomian gland functionACTA OPHTHALMOLOGICA, Issue 2010P VERSURA Purpose To evaluate the diagnostic performance of meibometry in classifying and quantifying Meibomian gland dysfunction(MGD) Methods Ninety-six patients with MGD (138 eyes, 62 women, 34 men) and 30 normal control subjects(55 eyes)were enrolled. Eighty six eyes were classified as high delivery (HD)-MGD (meibomian seborrhea/hypersecretory MGD), 52 as low delivery (LD)-MGD on the basis of expression quality scores and morphological signs. Direct Meibometry (DM) measurements were made with an MB550 Meibometer (Courage-Khazaka GmbH). Standard curves were constructed relating arbitrary Meibometer optical density units (AU). Integrated Meibometry (IM) was performed on scanned images of the lipid blots. Symptoms were scored by OSDI,Schirmer test I, Break Up Time (BUT), tear osmolarity (Tearlab, Ocusense), conjunctival scraping cytology were performed. Statistical analysis used SPSS 14.0 and MedCalc 5.0 Results AU values plotted on a log scale correlated highly with the lipid equivalent values (R2= 0.913). Significant differences were found between control subjects vs all MGD patients and between HD vs LD-MGD patients for all the parameters evaluated. In particular: controls: 300+/-121 AU (0.04+/-0.015 microliter), LD-MGD: 218+/-122 AU (0.03+/-0.015) and HD-MGD: 564+/-115 AU (0.07+0.015) (median+/-SD). Significant correlation was found DM vs IM (r=0.691,p<0.0001) and DM was shown to be correlated with BUT, OSDI score, scraping score and tear osmolarity, especially in LD-MGD patients. The selected DM diagnostic cut off for LD-MGD was <275 AU (sens 73, spec 60, PPV 63) and for HD-MGD was >450 AU; (sens 86, spec 87, PPV 91) Conclusion Meibometry is confirmed to be a reliable method to distinguish normal subjects from MGD subgroups with a good degree of accuracy [source] 4133: Dry eye and human tear lipid compositional, conformational and functional relationships using spectroscopyACTA OPHTHALMOLOGICA, Issue 2010D BORCHMAN Purpose Knowledge of the relationships among composition, conformation and function of tear film lipids could facilitate the development of therapies to alleviate symptoms related to meibomian gland dysfunction (MGD) and to diagnose the disease. Toward this goal, we used spectroscopic approaches to assess tear lipid composition and conformation relationships with age, sex and meibomian gland dysfunction. Methods Spectra of meibum from 41 patients diagnosed with MGD (Md) and 27 normal donors (Mn) were acquired. Results 1H-NMR spectra showed cholesterol esters were found to decrease by 21% with MGD. The number of double bonds/ester increased with age and MGD which indirectly relates to tear film stability. With age, the amount of CH2 groups increased twice as much as the C=C moieties and the C=C/CH2 and CH3/CH2 ratios were related to lipid order and indirectly related to meibum delivery. With the use of MALDI-TOF MS, we quantified and identified lipid components in Mn and Md such as cholesterol, hydrocarbons and wax esters with a sensitivity of 9 pmoles for each analyte. Sixty-nine of the 189 resolved peaks were unique to Md spectra compared to Mn spectra and were not due to waxes. Extra peaks in Md spectra may arise from increased lipid synthesis, bacteria or cellular debris. Conclusion It is reasonable that as the lipids become more ordered and more viscous with Md, less lipid flows out of the meibomian gland orifice and more casual lipid is present on the lid margin. The age- and disease-related changes in the physical and chemical characteristics of meibum lipids suggest that the C=C/CH2 and CH3/CH2 ratios may be more important than quantity in relation to tear film stability. [source] Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunctionCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2006P. Ena Summary Lower eyelid involvement occurs in 6% of patients with discoid lupus erythematosus (DLE). Eyelid lesions are rarely the initial manifestation of DLE. We describe a 25-year-old woman presenting with discoid lesions of the lower eyelids, staphylococcal blepharitis and Meibomian gland dysfunction, who later developed a discoid lesion on the chin. Histopathological and immunofluorescence studies of a biopsy specimen from this lesion established the diagnosis of DLE. We are unaware of any previously reported cases of DLE presenting with discoid eyelid lesions associated with staphylococcal blepharitis and Meibomian gland dysfunction. DLE should be considered as a differential diagnosis in chronic blepharitis that persists despite usual medical management and eyelid hygiene. Misdiagnosis may lead to eyelid margin deformities, necessitate a complicated full-thickness biopsy, and delay diagnosis of systemic lupus. [source] | ||||||||||