Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease Due to Meibomian Gland Disease.

PubMed

Steven, Philipp; Augustin, Albert J; Geerling, Gerd; Kaercher, Thomas; Kretz, Florian; Kunert, Kathleen; Menzel-Severing, Johannes; Schrage, Norbert; Schrems, Wolfgang; Krösser, Sonja; Beckert, Michael; Messmer, Elisabeth M

2017-11-01

Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction. Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6-8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI © ). From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6-8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16). In concordance with previous findings, 6-8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.

Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

PubMed

Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru

2015-06-01

In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function. Copyright © 2015 Elsevier Ltd. All rights reserved.

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye

PubMed Central

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

Purpose To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. Methods The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). Results At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). Conclusion A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye.

PubMed

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is

Abnormalities in the meibomian glands in patients with oral administration of anticancer combination drug-capsule TS-1(®): a case report.

PubMed

Mizoguchi, Shin; Okada, Yuka; Kokado, Masahide; Saika, Shizuya

2015-10-24

The anticancer TS-1(®) combination capsules of tegafur, gimeracil, and oteracil potassium (Taiho Pharmaceutical Co. Ltd, Japan) causes side effects, i. e., corneal epithelial disorder and dacryostenosis. However, its side effect on meibomian gland had not been reported. We observed morphological changes in the meibomian gland in patients taking TS-1(®) who exhibited punctate corneal epithelial defects to examine if dysfunction of meibomian glands is involved in the corneal epitheliopathy. Patients comprised two males and one female (age, 59-81 years). After starting oral TS-1(®) administration, patients developed subjective symptoms such as decreased visual acuity. Corneal epithelial disorder was seen in all six eyes of the three subjects exhibited, and lacrimal duct disorder was seen in one eye. Furthermore, meibomian gland loss and contraction were observed in all six eyes that exhibited meibomian gland disorder upon examination by using the MeiboPen(®). Results suggested that oral administration of TS-1(®) may cause meibomian gland disorder which potentially affect corneal epithelial homeostasis.

Regional Differences in Tear Film Stability and Meibomian Glands in Patients With Aqueous-Deficient Dry Eye.

PubMed

Koh, Shizuka; Ikeda, Chikako; Fujimoto, Hisataka; Oie, Yoshinori; Soma, Takeshi; Maeda, Naoyuki; Nishida, Kohji

2016-07-01

To noninvasively investigate regional differences in tear film stability and meibomian glands in patients with aqueous-deficient dry eye. Forty-nine dry eyes and 31 normal eyes were analyzed. A corneal topographer with a tear film scanning function was used for noninvasive tear film break-up time (NI-TFBUT) measurements and meibomian gland observations. The NI-TFBUT values and location of the first tear film break-up point were recorded in four quadrants. Meibomian gland loss was graded for each eyelid using meiboscores. Lid margin abnormality was scored from zero to four according to the number of existing abnormalities. The NI-TFBUT values and meiboscores were compared between two groups, and regional differences in NI-TFBUT values and meiboscores were analyzed. Also, the correlation between the NI-TFBUT and ocular surface examination results were investigated. The NI-TFBUT values and meiboscores were significantly lower and higher, respectively, for the dry eye group than for the normal group. In the dry eye group, the occurrence rate for first tear film break-up was the highest in the inferior nasal quadrant, and the mean meiboscore was significantly higher for the upper eyelids than for the lower eyelids. The NI-TFBUT and lid margin abnormality scores showed a weak negative correlation, and the NI-TFBUT values and meiboscores showed no correlation. Compared to normal eyes, aqueous-deficient dry eyes show significant regional differences in tear film stability and meibomian glands. Considering these regional differences, the overall observation of the ocular surface, including both upper and lower eyelids, will aid clinicians in understanding this condition better.

Reversibility of Gland Dropout and Significance of Eyelid Hygiene Treatment in Meibomian Gland Dysfunction.

PubMed

Yin, Yue; Gong, Lan

2017-03-01

To observe reversibility of meibomian gland (MG) dropout and analyze correlated factors and to compare the treatment efficiency with and without eyelid hygiene in patients with meibomian gland dysfunction (MGD). Consecutive 78 eyes of 78 MGD (stage 2-3) patients who finished follow-up examination after 1-month of treatment were recruited in this retrospective study. All patients were treated with artificial lubricant and eyelid hygiene. Related ocular surface evaluation and meibomian gland assessment were examined. There were 26 (33%) patients (included in group 1) who ignored doctors' order for eyelid hygiene, and 52 (67%) patients (included in group 2) were compliant. There was no statistical difference between group 1 (age, 44.4 ± 12.2) and group 2 (age, 38.9 ± 16.6) in characteristics and pretreatment clinical indexes. However, after 1-month of treatment, only the ocular surface disease index of group 1 improved (P = 0.048), whereas all clinical indexes of group 2, except the Schirmer test result, improved (including expressibility, all P < 0.05). A 5% decrease in MG dropout of both upper (5.4%) and lower (4.6%) eyelids in group 2 was observed. Improvement in upper-eyelid dropout and expressibility were the predictors of lower-eyelid dropout improvement. The reversibility had no correlation with age, sex, pretreatment MGD stage, disease duration, and use of topical antiinflammation medication. With expressibility-improving treatment, MG dropout was reversible to some extent. Eyelid hygiene is an efficient treatment of MGD; however, there is a need for ophthalmologists to instruct patients on conduct and supervise patients' compliance.

Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PubMed

Wladis, Edward J; Bradley, Elizabeth A; Bilyk, Jurij R; Yen, Michael T; Mawn, Louise A

2016-03-01

To review the existing medical literature on the role of oral antibiotics in the management of ocular surface disease (OSD) that arises from disorders of the meibomian glands and to assess the efficacy of oral antibiotics in the management of this common ocular disease. A literature search was last conducted on August 12, 2015, in the PubMed and Cochrane databases for English-language original research investigations that evaluated the role of doxycycline, minocycline, and azithromycin in OSD among adult patients. The searches identified 87 articles, and 8 studies ultimately met the criteria outlined for this assessment. The 8 studies identified in the search documented an improvement in meibomian gland-related OSD after treatment with these agents, although side effects were common. This search identified only 1 randomized, controlled trial to assess the efficacy of these medications. Although oral antibiotics are used commonly in the management of OSD, there is no level I evidence to support their use. There are only a few studies that have assessed the efficacy of oral antibiotics in clinically meaningful ways in the management of OSD that arises from disorders of the meibomian glands. The current level of evidence is insufficient to conclude that antibiotics are useful in managing OSD arising from disorders of the meibomian glands. The few existing studies on the topic indicate that oral antibiotics may be an effective treatment for OSD that results from meibomian gland disease. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Bioimage informatics approach to automated meibomian gland analysis in infrared images of meibography

PubMed Central

Celik, Turgay; Lee, Hwee Kuan; Petznick, Andrea; Tong, Louis

2013-01-01

Background Infrared (IR) meibography is an imaging technique to capture the Meibomian glands in the eyelids. These ocular surface structures are responsible for producing the lipid layer of the tear film which helps to reduce tear evaporation. In a normal healthy eye, the glands have similar morphological features in terms of spatial width, in-plane elongation, length. On the other hand, eyes with Meibomian gland dysfunction show visible structural irregularities that help in the diagnosis and prognosis of the disease. However, currently there is no universally accepted algorithm for detection of these image features which will be clinically useful. We aim to develop a method of automated gland segmentation which allows images to be classified. Methods A set of 131 meibography images were acquired from patients from the Singapore National Eye Center. We used a method of automated gland segmentation using Gabor wavelets. Features of the imaged glands including orientation, width, length and curvature were extracted and the IR images enhanced. The images were classified as ‘healthy’, ‘intermediate’ or ‘unhealthy’, through the use of a support vector machine classifier (SVM). Half the images were used for training the SVM and the other half for validation. Independently of this procedure, the meibographs were classified by an expert clinician into the same 3 grades. Results The algorithm correctly detected 94% and 98% of mid-line pixels of gland and inter-gland regions, respectively, on healthy images. On intermediate images, correct detection rates of 92% and 97% of mid-line pixels of gland and inter-gland regions were achieved respectively. The true positive rate of detecting healthy images was 86%, and for intermediate images, 74%. The corresponding false positive rates were 15% and 31% respectively. Using the SVM, the proposed method has 88% accuracy in classifying images into the 3 classes. The classification of images into healthy and unhealthy

Long-Term (3 Year) Effects of a Single Thermal Pulsation System Treatment on Meibomian Gland Function and Dry Eye Symptoms.

PubMed

Greiner, Jack V

2016-03-01

The present study examined the long-term (3 years) effects of a single (12 min) thermal pulsation system (TPS) treatment on symptomatic patients with evaporative dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). In this prospective, cohort, observational, single-center study design, signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT]) and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes) with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS treatment using LipiFlow. Meibomian gland secretion scores increased from BL (4.5±0.8) to 1 month (12.0±1.1, P≤0.001). Improvement persisted at 3 years (18.4±1.4) relative to BL (P≤0.001). Meibomian gland secretion scores in all regions of the lower eyelid were improved over BL at 1 month (nasal [P≤0.001], central [P≤0.001], temporal [P≤0.01]) and 3 years (nasal [P≤0.001], central [P≤0.001], temporal [P≤0.001]). TBUT increased from BL (4.1±0.4) to 1 month (7.9±1.4, P≤0.05) but was not significantly different than BL at 3 years (4.5±0.6, P>0.05). The OSDI scores decreased from BL (26.0±4.6) to 1 month (14.7±4.3, P≤0.001) but returned to BL levels at 3 years (22.5±5.4, P>0.05). The SPEED scores decreased from BL (13.4±1.0) to 1 month (6.5±1.3, P≤0.001), and this improvement persisted at 3 years (9.5±1.6, P≤0.001). Thermal pulsation may be a uniquely efficacious treatment option for DED secondary to MGD in that a single 12-min procedure is associated with significant improvement in MGS and SPEED scores for up to 3 years.

Infrared imaging of meibomian glands and evaluation of the lipid layer in Sjögren's syndrome patients and nondry eye controls.

PubMed

Menzies, Kara L; Srinivasan, Sruthi; Prokopich, C Lisa; Jones, Lyndon

2015-01-08

The purpose of this study was to evaluate meibomian gland dropout and lipid layer thickness (LLT) in patients with and without Sjögren's syndrome dry eye (SS). We recruited 11 participants with SS (males/females [M/F], 1:10; mean age = 56.0 ± 9.1 years) and 10 control subjects without dry eye (M/F, 3:7; mean age = 58.5 ± 4.7 years). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The LLT was assessed using the Tearscope Plus based on the appearance of the lipid layer. Noninvasive tear break-up time (NITBUT) also was measured. The lower and upper lids were everted, and the meibomian glands were imaged using the infrared camera of the Keratograph 4. A meibomian gland dropout score due to gland loss was obtained. Statistical analysis was conducted using the Mann-Whitney U test and correlations were determined using Spearman rank correlations. Of the SS participants, 100% reported ocular and oral dryness symptoms in the AECC questionnaire. The SS group recorded a higher OSDI score (median = 48.00, interquartile range [IQR] 23.0-56.2 vs. 2.1, IQR 0.0-2.6; P < 0.001), reduced LLT (median [IQR] = 15.0 [15.0-15.0] vs. 60.0 [45.0-100.0] nm; P = 0.001), and lower NITBUT (median [IQR] = 3.7 [2.5-4.2] vs. 9.5 [6.4-17.6] sec; P < 0.001) compared to the controls. Digital meibomian gland dropout score (% dropout) was significantly higher for the SS group (16.0% [IQR 12.1-40.0%] vs. 6.7% [IQR 1.5-12.7%]; P = 0.01). Subjective meibomian gland dropout score (0-6 score) was significantly higher for the SS group (median [IQR] = 1.5 [1.0-4.0] vs. 1.0 [0.0-1.25]; P = 0.03). Patients with SS showed higher meibomian gland dropout scores and reduced LLT and NITBUT, which likely contribute to the severe dry eye symptoms reported by SS subjects. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Compensatory increases in tear volume and mucin levels associated with meibomian gland dysfunction caused by stearoyl-CoA desaturase-1 deficiency.

PubMed

Inaba, Takaaki; Tanaka, Yasuhisa; Tamaki, Shusaku; Ito, Tomotaka; Ntambi, James M; Tsubota, Kazuo

2018-02-20

The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva. Previous histopathological analysis had revealed atrophy and loss of meibomian glands; taken together with the increased goblet cell and MUC5AC expression in the conjunctiva reported here, these findings suggest that the tear volume and mucin levels secreted are enhanced in the absence of lipid secretion as a compensatory mechanism. The expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO mice. Thus, these results provide new pathophysiological mechanisms to pursue with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a compensatory increase in the tear volume and mucin levels associated with changes in expression of lipid metabolism genes. These results may be useful as a new concept for dry eye treatment strategies.

Efficacy of an artificial tear emulsion in patients with dry eye associated with meibomian gland dysfunction.

PubMed

Sindt, Christine W; Foulks, Gary N

2013-01-01

The aim of the study reported here was to assess the efficacy of an artificial tear emulsion for the treatment of dry eye associated with meibomian gland dysfunction (MGD). At five clinics, patients completed a 1-week treatment with their habitual topical therapy and then a 4-week treatment with open-label study medication: Systane® Balance Lubricant Eye Drops (Alcon, Alcon Inc, Fort Worth, TX, USA). Subjective assessments included a preference survey, the Impact of Dry Eye in Everyday Life questionnaire, and the Work Productivity and Activity Impairment questionnaire. Objective assessments by unmasked investigators included visual acuity, meibomian gland expression and dropout, tear film breakup time, corneal staining, and dosing frequency. At baseline, the 49 patients had mean meibomian gland expression grades and gland dropout that indicated mild to moderate MGD. Patients administered their habitual therapy 2.5 ± 1.3 times per day. After 4 weeks of study medication, the Impact of Dry Eye in Everyday Life questionnaire results indicated statistically and clinically significant improvements. Fewer than half of the participants were employed, limiting the usefulness of the Work Productivity and Activity Impairment questionnaire. Visual acuity remained statistically similar, while corneal staining and tear film breakup time improved significantly (P < 0.05) but modestly. The outcomes were achieved with 1.9 ± 1.1 doses per day of study medication, a significantly lower frequency than the habitual frequency (P < 0.001). The most common medication-related adverse event was blurred vision (3/49 patients, 6.1%). At study conclusion, 27/44 (61.4%) survey respondents preferred the study medication to their habitual therapy. The artificial tear emulsion was effective for treating the signs and symptoms of dry eye in MGD patients.

Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction.

PubMed

Amano, Shiro; Inoue, Kenji

2017-01-01

To prospectively evaluate the effect of topical diquafosol sodium on eyes with dry eye disease (DED) and meibomian gland dysfunction (MGD). The subjects were consecutive patients diagnosed with both DED and MGD at Inouye Eye Hospital between March and September of 2016. The subjects were administered topical 3% diquafosol sodium ophthalmic solution six times a day for 3 months. At each study visit, subjects underwent slit-lamp examination and completed MGD symptoms and dry eye-related quality of life score (DEQS) questionnaires. Meibum quality (meibum score) and meibomian gland loss (meiboscore) were evaluated. Tear lipid layer thickness was measured in both eyes with an ocular surface interferometer immediately after clinic arrival and 20 minutes after instillation of one drop of topical diquafosol. Thirteen patients (3 men, 10 women) with a mean age of 69.5±8.3 years completed the 3-month study. The number of telangiectasia and plugged meibomian gland orifices significantly decreased from baseline after 1 month of diquafosol use. The meibum score and the meiboscore significantly decreased from baseline at 3 months. Also, the lipid layer thickness was greater after diquafosol administration than before administration at baseline and 1, 2, and 3 months by 12.2, 11.5, 9.5, and 17.0 nm, respectively, but this difference was only significant at 3 months ( p =0.039). The DEQS ocular symptom ( p =0.065) and MGD questionnaire ( p =0.081) scores tended to be lower than baseline at 3 months. Diquafosol sodium ophthalmic solution improves DED- and MGD-related signs in eyes with MGD.

Identification of fatty acids and fatty acid amides in human meibomian gland secretions.

PubMed

Nichols, Kelly K; Ham, Bryan M; Nichols, Jason J; Ziegler, Corrie; Green-Church, Kari B

2007-01-01

The complex superficial lipid layer of the tear film functions to prevent evaporation and maintain tear stability. Although classes of lipids found in the tear film have been reported, individual lipid species are currently being studied with more sophisticated. The purpose of this work was to show the identification of fatty acids and the fatty acid amides in human meibomian gland secretions by using electrospray mass spectrometry. methods. Human meibomian gland secretions (meibum) were analyzed by electrospray quadrupole time-of-flight mass spectrometry (positive- and negative-ion mode). Accurate mass determination and collision-induced dissociation of meibum, and lipid standards were used to identify lipid species. Mass analysis of meibum in an acidic chloroform-methanol solution in positive-ion mode revealed a mass peak of m/z 282.3, which was identified as the protonated molecule of oleamide [C(18)H(35)NO+H](+). The high-resolution mass analysis of the m/z 282.2788 peak (oleamide) demonstrated a mass accuracy of 3.2 parts per million (ppm). Collision-induced dissociation of this species from meibum, compared with an oleamide standard, confirmed its identification. Myristic, palmitic, stearic, and oleic free fatty acids were identified in a similar manner, as were the other fatty acid amides (myristamide, palmitamide, stearamide, and erucamide). The findings indicate that oleamide (cis-9-octadecenamide), an endogenous fatty acid primary amide, is a predominant component of meibum when examined by electrospray mass spectrometry. The novel finding of oleamide and other members of the fatty acid amide family in the tear film could lead to additional insights into the role of fatty acid amide activity in human biological systems and may indicate a new function for this lipid class of molecules in ocular surface signaling and/or in the maintenance of the complex tear film.

Influence of Meibomian Gland Expression Methods on Human Lipid Analysis Results.

PubMed

Kunnen, Carolina M E; Brown, Simon H J; Lazon de la Jara, Percy; Holden, Brien A; Blanksby, Stephen J; Mitchell, Todd W; Papas, Eric B

2016-01-01

To compare the lipid composition of human meibum across three different meibum expression techniques. Meibum was collected from five healthy non-contact lens wearers (aged 20-35 years) after cleaning the eyelid margin using three meibum expression methods: cotton buds (CB), meibomian gland evaluator (MGE) and meibomian gland forceps (MGF). Meibum was also collected using cotton buds without cleaning the eyelid margin (CBn). Lipids were analyzed by chip-based, nano-electrospray mass spectrometry (ESI-MS). Comparisons were made using linear mixed models. Tandem MS enabled identification and quantification of over 200 lipid species across ten lipid classes. There were significant differences between collection techniques in the relative quantities of polar lipids obtained (P<.05). The MGE method returned smaller polar lipid quantities than the CB approaches. No significant differences were found between techniques for nonpolar lipids. No significant differences were found between cleaned and non-cleaned eyelids for polar or nonpolar lipids. Meibum expression technique influences the relative amount of phospholipids in the resulting sample. The highest amounts of phospholipids were detected with the CB approaches and the lowest with the MGE technique. Cleaning the eyelid margin prior to expression was not found to affect the lipid composition of the sample. This may be a consequence of the more forceful expression resulting in cell membrane contamination or higher risk of tear lipid contamination as a result of reflex tearing. Copyright © 2016 Elsevier Inc. All rights reserved.

Randomised controlled trial of topical antibacterial Manuka (Leptospermum species) honey for evaporative dry eye due to meibomian gland dysfunction.

PubMed

Albietz, Julie M; Schmid, Katrina L

2017-11-01

The aim was to evaluate the efficacy of standardised Manuka (Leptospermum species) antibacterial honey as adjunctive twice daily treatment to conventional therapy (warm compresses, lid massage and preservative-free lubricant), in participants with evaporative dry eye due to moderate to advanced meibomian gland dysfunction. This prospective, open-label study involved 114 participants. After two weeks of conventional therapy participants were randomised to one of three treatment groups: Optimel Antibacterial Manuka Eye Gel (98 per cent Leptospermum species honey) plus conventional therapy (n = 37), Optimel Manuka plus Lubricant Eye Drops (16 per cent Leptospermum species honey) plus conventional therapy (n = 37) and a control (conventional therapy) (n = 40). Clinical evaluations performed at baseline and Week 8 included: symptom scores (Ocular Surface Disease Index, Ocular Comfort Index), daily lubricant use, tear assessments (break-up time, secretion, osmolarity and InflammaDry), corneal sensation, ocular surface staining, meibomian gland secretion quality and expressibility, bulbar conjunctival, limbal and lid marginal redness and eyelid marginal bacterial cultures and colony counts. Significant improvements (p ≤ 0.05) occurred at Week 8 in symptoms, tear break-up time, staining, tear osmolarity, meibum quality and bulbar, limbal and lid margin redness for all treatments. Improvement in staining was significantly greater with Optimel 16 per cent drops (p = 0.035). Significant improvements (p < 0.05) in meibomian gland expressibility and InflammaDry occurred for both Optimel treatments. Optimel 98 per cent gel was significantly more effective in improving meibum quality (p = 0.005) and gland expressibility (p = 0.042). Total eyelid marginal bacterial colony counts reduced significantly with Optimel 16 per cent drops (p = 0.03) but not the other treatments. Staphylococcus epidermidis counts reduced significantly with Optimel 16

Meibomian Gland Dysfunction Determines the Severity of the Dry Eye Conditions in Visual Display Terminal Workers

PubMed Central

Dong, Nuo; Yang, Fan; Lin, Zhirong; Shang, Xumin; Li, Cheng

2014-01-01

Objective To explore meibomian gland dysfunction (MGD) may determine the severity of dry eye conditions in visual display terminal (VDT) workers. Methodology Prospective, case-control study carried out in China.106 eyes of 53 patients (VDT work time >4 hour per day) were recruited as the Long time VDT group; 80 eyes of 40 control subjects (VDT work time ≤4 hour per day) served as the Short time VDT group. A questionnaire of Ocular Surface Disease Index (OSDI) and multiple tests were performed. Three dry eye tests: tear film breakup time (BUT), corneal fluorescein staining, Schirmer I test; and three MGD parameters: lid margin abnormality score, meibum expression assessment (meibum score), and meibomian gland dropout degree (meiboscore) using Keratograph 5 M. Principal Findings OSDI and corneal fluorescein score were significantly higher while BUT was dramatically shorter in the long time VDT group than the short time VDT group. However, the average of Schirmer tear volumes was in normal ranges in both groups. Interestingly, the three MGD parameters were significantly higher in the long time VDT group than the short time one (P<0.0001). When 52 eyes with Schirmer <10 mm and 54 eyes with Schirmer ≥10 mm were separated from the long time VDT workers, no significant differences were found between the two subgroups in OSDI, fluorescein staining and BUT, as well as the three MGD parameters. All three MGD parameters were positively correlated with VDT working time (P<0.0001) and fluorescein scores (P<0.0001), inversely correlated with BUT (P<0.05), but not correlated with Schirmer tear volumes in the VDT workers. Conclusions Our findings suggest that a malfunction of meibomian glands is associated with dry eye patients in long term VDT workers with higher OSDI scores whereas some of those patients presenting a normal tear volume. PMID:25144638

Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study.

PubMed

Foulks, Gary N; Borchman, Douglas; Yappert, Marta; Kakar, Shelley

2013-01-01

Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid-lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-NMR) spectrometer. Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy-principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels

Functional and Morphologic Changes of Meibomian Glands in an Asymptomatic Adult Population.

PubMed

Yeotikar, Nisha S; Zhu, Hua; Markoulli, Maria; Nichols, Kelly K; Naduvilath, Thomas; Papas, Eric B

2016-08-01

The aim of the study was to understand natural changes of meibomian glands (MG) that occur with aging in the absence of any ocular pathology or ocular discomfort symptoms, to differentiate between "age normal" and pathologic or dysfunctional changes of the MG. A total of 185 subjects (109 females) with no pre-existing ocular and systemic abnormalities were recruited and divided into four age groups: 25 to 34, 35 to 44, 45 to 54, and 55 to 66 years. At a single visit, the following MG measures were collected: meibum quality (MQ) and MG expressibility (MGE) of the lower lid, and MG drop-out score (meiboscale) using infrared meibography of the upper and lower lids. Assessments of anterior eye, tear function variables, noninvasive and invasive tear breakup time (TBUT), corneal integrity, and lid wiper epitheliopathy were also performed during the visit. An Ocular Surface Disease Index (OSDI) questionnaire was used to record dry eye symptoms. Meibum lipids samples were collected and analyzed. A majority of the study population (61%) was asymptomatic. There was a significant worsening in the MQ (P< 0.048), MGE (P < 0.03), and meiboscale (P < 0.01) with increasing age. Significant increase was observed in anterior blepharitis (P < 0.001) and telangiectasia (P< 0.02) with aging. Interestingly, tear osmolarity decreased significantly (P < 0.001), while tear meniscus height (P < 0.001) and invasive TBUT (P = 0.02) increased with increase in age. There was no significant association between MG variables and sex, ocular discomfort symptoms, or meibum lipids classes. Progressive MG loss occurs normally with age accompanied by reduced quality and quantity of the meibum produced. However, clinical presentation of ocular discomfort symptoms is stalled without corresponding disruption to tear function.

The effects of 3% diquafosol sodium eye drop application on meibomian gland and ocular surface alterations in the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

PubMed

Ikeda, Keisuke; Simsek, Cem; Kojima, Takashi; Higa, Kazunari; Kawashima, Motoko; Dogru, Murat; Shimizu, Takahiko; Tsubota, Kazuo; Shimazaki, Jun

2018-04-01

The purpose of the study is to investigate the effect of 3% diquafosol sodium eye drops on meibomian gland and ocular surface alterations in the superoxide dismutase-1 (Sod1 -/- ) mice in comparison to the wild-type mouse. Three percent diquafosol sodium eye drop was instilled to 20 eyes of 10 50-week-old male Sod1 -/- mice and 22 eyes of 11 C57BL/6 strain 50-week-old wild-type (WT) male mice six times a day for 2 weeks. Aqueous tear secretion quantity was measured with phenol red-impregnated cotton threads without anesthesia. Tear film stability and corneal epithelial damage were assessed by fluorescein and lissamine green staining. We also performed oil red O (ORO) lipid staining to evaluate the lipid changes in the meibomian glands. Meibomian gland specimens underwent hematoxylin and eosin staining to examine histopathological changes and meibomian gland acinar unit density after sacrifice. Immunohistochemistry staining was performed using cytokeratin 4, cytokeratin 13, and transglutaminase-1 antibodies. Quantitative real-time polymerase chain reaction for cytokeratin 4, cytokeratin 13, and transglutaminase-1 mRNA expression was also performed. The aqueous tear quantity, the mean tear film breakup time, and the number of lipid droplets significantly improved in the Sod1 -/- mice with treatment. The mean meibomian acinar unit density did not change in the Sod1 -/- mice and WT mice after treatment. Application of 3% diquafosol sodium eye drop significantly decreased the corneal fluorescein and lissamine green staining scores in the Sod1 -/- mice after 2 weeks. We showed a notable increase in cytokeratin 4, cytokeratin 13 immunohistochemistry staining, and cytokeratin 4, cytokeratin 13 mRNA expressions with a marked decrease in immunohistochemistry staining and significant decline in mRNA expression of transglutaminase-1 after 3% diquafosol sodium treatment. Topical application of 3% diquafosol sodium eye drop improved the number of lipid droplets, tear stability

The spectrophotometric sulfo-phospho-vanillin assessment of total lipids in human meibomian gland secretions.

PubMed

McMahon, Anne; Lu, Hua; Butovich, Igor A

2013-05-01

Human meibomian gland secretions (meibum) are the major lipid component of the human preocular tear film. The predominant lipid classes found in meibum include waxes (WE), cholesteryl esters (CE), and varying amounts of cholesterol (Chl). The classical sulfo-phospho-vanillin assay (SPVA), adapted for a microplate reader, was used to quantitate lipids in meibum. To account for varying reactivities of different lipids in SPVA, a model meibomian lipid mixture (MMx) that approximated the WE/CE/Chl composition of meibum was developed and used to quantitate meibomian lipids. The overall SPV responses of MMx and meibum were found to be close, with similar intermediate and final reaction products for both. Saturated WE that had not been expected to be reactive were found to be SPV-positive. A reaction mechanism for these compounds in SPVA which involves the formation of alkenyl ethers is proposed and discussed. Tested proteins were non-reactive in SPVA. Thus, by comparing the results of gravimetric analyses of meibum samples with the results of a properly calibrated SPVA, it was estimated that the SPV-reactive lipid content of dry meibum in tested samples was about 78 % (w/w). The SPV method can also be adopted for analyzing other types of complex lipids secretions, such as sebum, as well as whole lipid extracts from other lipid-enriched organs and tissues, if proper standards are chosen.

The Spectrophotometric Sulfo-Phospho-Vanillin Assessment of Total Lipids in Human Meibomian Gland Secretions

PubMed Central

McMahon, Anne; Lu, Hua

2013-01-01

Human meibomian gland secretions (meibum) are the major lipid component of the human preocular tear film. The predominant lipid classes found in meibum include waxes (WE), cholesteryl esters (CE), and varying amounts of cholesterol (Chl). The classical sulfo-phospho-vanillin assay (SPVA), adapted for a microplate reader, was used to quantitate lipids in meibum. To account for varying reactivities of different lipids in SPVA, a model meibomian lipid mixture (MMx) that approximated the WE/CE/Chl composition of meibum was developed and used to quantitate meibomian lipids. The overall SPV responses of MMx and meibum were found to be close, with similar intermediate and final reaction products for both. Saturated WE that had not been expected to be reactive were found to be SPV-positive. A reaction mechanism for these compounds in SPVA which involves the formation of alkenyl ethers is proposed and discussed. Tested proteins were non-reactive in SPVA. Thus, by comparing the results of gravimetric analyses of meibum samples with the results of a properly calibrated SPVA, it was estimated that the SPV-reactive lipid content of dry meibum in tested samples was about 78 % (w/w). The SPV method can also be adopted for analyzing other types of complex lipids secretions, such as sebum, as well as whole lipid extracts from other lipid-enriched organs and tissues, if proper standards are chosen. PMID:23345137

Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

PubMed

Miyake, Hideki; Oda, Tomoko; Katsuta, Osamu; Seno, Masaharu; Nakamura, Masatsugu

2016-06-01

A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD). Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model. After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis. We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.

In vitro effects of sex hormones in human meibomian gland epithelial cells.

PubMed

Schröder, Antje; Abrar, Daniel B; Hampel, Ulrike; Schicht, Martin; Paulsen, Friedrich; Garreis, Fabian

2016-10-01

Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (β-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -β (ERα, ERβ) and progesterone receptor (PR) in HMGEC. PR, ERα and ERβ expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERβ. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in the evaporation rate of tear film after digital expression of meibomian glands in patients with and without dry eye.

PubMed

Arciniega, Juan Carlos; Wojtowicz, Jadwiga Cristina; Mohamed, Engy Mostafa; McCulley, James Parker

2011-08-01

To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye. Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute. An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression. Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.

Characterization of the mucocutaneous junction of the human eyelid margin and meibomian glands with different biomarkers.

PubMed

Tektaş, Ozan Yüksel; Yadav, Ajay; Garreis, Fabian; Schlötzer-Schrehardt, Ursula; Schicht, Martin; Hampel, Ulrike; Bräuer, Lars; Paulsen, Friedrich

2012-09-01

To investigate the morphology of the human eyelid margin and the presence of different cytokeratins, mucins and stem cell markers within the skin epithelium, mucocutaneous junction (MCJ) and palpebral conjunctiva. Eyelids of body donors were investigated histologically and ultrastructurally as well as by immunohistochemical methods using antibodies to cytokeratins 1, 4, 7, 8, 10, 13, 14, 15, and 19; mucins MUC1, MUC4, and MUC5AC and potential stem cell markers K15, BCRP/ABCG2, integrin β1, and N-cadherin. The expression pattern of cytokeratins, mucins and stem cell markers varied across the different epithelia of the human eyelid. Within the MCJ, CK7, 15 and 19 were absent, whereas the epithelium reacted positive to antibodies to CK1, 4, 8, 10, 13 and 14. Reactivity was also observed for MUC1 and MUC4, but not for MUC5AC. No reactivity was determined for K15, BCRP/ABCG2 and integrin β1 in the area of the MCJ epithelium but a strong reactivity was present for N-cadherin. The present immunohistochemical findings lead to a better characterization of the MCJ. Additionally, the knowledge of distribution of biomarkers like cytokeratins, mucins and stem cells can be useful in the investigation of MCJ disturbances which occur in several disorders of the meibomian glands and the lid epithelium in the course of dry eye syndrome and especially meibomian gland dysfunction. Copyright © 2012 Elsevier GmbH. All rights reserved.

Characterization of Rat Meibomian Gland Ion and Fluid Transport

PubMed Central

Yu, Dongfang; Davis, Richard M.; Aita, Megumi; Burns, Kimberlie A.; Clapp, Phillip W.; Gilmore, Rodney C.; Chua, Michael; O'Neal, Wanda K.; Schlegel, Richard; Randell, Scott H.; C. Boucher, Richard

2016-01-01

Purpose We establish novel primary rat meibomian gland (MG) cell culture systems and explore the ion transport activities of the rat MG. Methods Freshly excised rat MG tissues were characterized as follows: (1) mRNA expression of selected epithelial ion channels/transporters were measured by RT-PCR, (2) localization of epithelial sodium channel (ENaC) mRNAs was performed by in situ hybridization, and (3) protein expression and localization of βENaC, the Na+/K+/Cl− cotransporter (NKCC), and the Na+/K+ ATPase were evaluated by immunofluorescence. Primary isolated rat MG cells were cocultured with 3T3 feeder cells and a Rho-associated kinase (ROCK) inhibitor (Y-27632) for expansion. Passaged rat MG cells were cultured as planar sheets under air-liquid interface (ALI) conditions for gene expression and electrophysiologic studies. Passaged rat MG cells also were cultured in matrigel matrices to form spheroids, which were examined ultrastructurally by transmission electron microscopy (TEM) and functionally using swelling assays. Results Expression of multiple ion channel/transporter genes was detected in rat MG tissues. β-ENaC mRNA and protein were localized more to MG peripheral acinar cells than central acinar cells or ductular epithelial cells. Electrophysiologic studies of rat MG cell planar cultures demonstrated functional sodium, chloride, and potassium channels, and cotransporters activities. Transmission electron microscopic analyses of rat MG spheroids revealed highly differentiated MG cells with abundant lysosomal lamellar bodies. Rat MG spheroids culture-based measurements demonstrated active volume regulation by ion channels. Conclusions This study demonstrates the presence and function of ion channels and volume transport by rat MG. Two novel primary MG cell culture models that may be useful for MG research were established. PMID:27127933

Dyslipidemia and its association with meibomian gland dysfunction.

PubMed

Braich, Puneet S; Howard, Mary K; Singh, Jorawer S

2016-08-01

Abnormal serum lipid levels significantly increase the risk for cardiovascular disease. Furthermore, abnormal compositions of cholesterol in glandular secretions have been hypothesized as an etiology for meibomian gland dysfunction, yet this relationship has not been well studied in clinical settings. The primary purpose of this study was to determine if there is an association between dyslipidemia and meibomian gland dysfunction (MGD). The secondary purpose was to identify the factors, if any, that play a role in this association. A case-control study was performed between October 2013 and February 2015 which recruited 109 patients with MGD and 115 control patients without MGD. All participants were of Indian descent and had no history of dyslipidemia. Basic demographic information was collected as well as fasting levels of serum glucose, creatinine, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). To calculate differences between groups, Z test or Student t test were used. A stepwise logistic regression model was used to calculate the estimates of odds ratios (ORs), where MGD was the dependent variable, making the independent variables consist of sex, age, body mass index (BMI), triglycerides ≥150 mg/dL, total cholesterol ≥200 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, serum glucose, and serum creatinine. Dyslipidemia, defined by either a fasting total cholesterol level of ≥ 200 mg/dL, triglycerides ≥150 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, was detected in 70 cases (64 %) and 21 controls (18 %), P < 0.001. Mean levels of triglycerides, total cholesterol, LDL, and HDL were 98.5 ± 42.1, 203.1 ± 13.2, 126.1 ± 10.2, and 53.3 ± 4.2 mg/dL, respectively, in cases and 82.3 ± 36.5, 156.6 ± 14.5, 92.2 ± 12.4, 45.8 ± 2.6 mg/dL, respectively, in controls. All differences were statistically significant (P < 0.05). MGD was significantly associated with age >65�

Infrared thermography in the evaluation of meibomian gland dysfunction.

PubMed

Su, Tai-Yuan; Ho, Wei-Ting; Chiang, Shu-Chiung; Lu, Chien-Yi; Chiang, Huihua Kenny; Chang, Shu-Wen

2017-07-01

To evaluate meibomian gland dysfunction (MGD) by infrared thermography. An observational study was conducted at the Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan. Participants included 89 MGD patients (30 in Grade 1, 49 in Grade 2, and 10 in Grade 3) and 65 controls. The close-eye thermographic images of the eyelid were obtained noninvasively by infrared thermography. Temperatures at 8 regions of interest (ROIs) of the eyelid margin and a reference temperature at the center of the upper eyelid were measured. The temperature ratio was defined as the temperature of ROI divided by the reference temperature. Eyelid margin temperature measured by infrared thermography increased from temporal side (ROI 1) to the nasal side (ROI 8) of the eye in both MGD patients and control groups. The temperature ratios were significantly higher in MGD participants than in controls, especially at ROI 8. The eyelid margin temperature measured by infrared thermography was higher in MGD participants. Further development of this infrared thermography system may become a rapid and non-invasive tool for MGD screening. Copyright © 2016. Published by Elsevier B.V.

Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

PubMed Central

Ibrahim, Osama M. A.; Dogru, Murat; Matsumoto, Yukihiro; Igarashi, Ayako; Kojima, Takashi; Wakamatsu, Tais Hitomi; Inaba, Takaaki; Shimizu, Takahiko; Shimazaki, Jun; Tsubota, Kazuo

2014-01-01

Purpose The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse. Methods Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results Corneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice. Conclusions Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations. PMID:25036096

Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study.

PubMed

Toyos, Rolando; McGill, William; Briscoe, Dustin

2015-01-01

The purpose of this study was to determine the clinical benefits of intense-pulsed-light therapy for the treatment of dry-eye disease caused by meibomian gland dysfunction (MGD). MGD is the leading cause of evaporative dry eye disease. It is currently treated with a range of methods that have been shown to be only somewhat effective, leading to the need for advanced treatment options. A retrospective noncomparative interventional case series was conducted with 91 patients presenting with severe dry eye syndrome. Treatment included intense-pulsed-light therapy and gland expression at a single outpatient clinic over a 30-month study. Pre/post tear breakup time data were available for a subset of 78 patients. For all patients, a specially developed technique for the treatment of dry eye syndrome was applied as a series of monthly treatments until there was adequate improvement in dry eye syndrome symptoms by physician judgment, or until patient discontinuation. Primary outcomes included change in tear breakup time, self-reported patient satisfaction, and adverse events. Physician-judged improvement in dry eye tear breakup time was found for 68 of 78 patients (87%) with seven treatment visits and four maintenance visits on average (medians), and 93% of patients reported post-treatment satisfaction with degree of dry eye syndrome symptoms. Adverse events, most typically redness or swelling, were found for 13% of patients. No serious adverse events were found. Although preliminary, study results of intense-pulsed-light therapy treatment for dry eye syndrome caused by meibomian gland dysfunction are promising. A multisite clinical trial with a larger sample, treatment comparison groups, and randomized controlled trials is currently underway.

The function and morphology of Meibomian glands in patients with thyroid eye disease: a preliminary study.

PubMed

Wang, Chia-Yu; Ho, Ren-Wen; Fang, Po-Chiung; Yu, Hun-Ju; Chien, Chun-Chih; Hsiao, Chang-Chun; Kuo, Ming-Tse

2018-04-12

To investigate function and morphology of the meibomian gland (MG) in patients with thyroid eye disease (TED). In this prospective case series study, patients with unilateral or bilateral TED were consecutively enrolled. The diagnosis of TED was based on the typical orbital findings and/or radiographic evidence. The disease activity of TED was classified according to the clinical activity score (CAS). Degrees of lagophthalmos and exophthalmos, blinking rates, and results of the Schirmer test 1 were also recorded. All patients completed the SPEED questionnaire and underwent MG assessment, including lipid layer thickness (LLT), MG dropout (MGd), and MG expression. In total 31 eyes from 17 patients with unilateral or bilateral TED were included. Patients were divided into inactive TED (CAS 0-1; 20 eyes from 11 patients) and active TED (CAS 2-3, 11 eyes from 6 patients) groups. MGd was significantly more severe in the active TED than the inactive TED group [Median (Inter-quartile region): 3.0 (2.0-3.0) vs. 2.0 (1.0-2.0) degree, P = 0.04]. However, patients with active TED had thicker LLT than those with inactive TED (90.0 [80.0-100.0] vs. 65.0 [47.8-82.5] nm, P = 0.02), and LLT was positively correlated with lagophthalmos (r = 0.37, P = 0.04). Patients with active TED had more severe MGd, but thicker LLT. Active TED may cause periglandular inflammation of MGs, leading to MGd, but compensatory secretion from residual MGs and lagophthalmos-induced forceful blinking might temporarily release more lipids over the tear film.

Induced videokeratography alterations in patients with excessive meibomian secretions.

PubMed

Markomanolakis, Marinos M; Kymionis, George D; Aslanides, Ioannis M; Astyrakakis, Nikolaos; Pallikaris, Ioannis G

2005-01-01

To describe lipid-induced specific videokeratographic (VKG) corneal changes and subsequent resolution after eyelid washing. VKG was performed with C-Scan corneal topography. In all patients an excessive meibomian gland lipid secretion was found with or without coexistent chronic posterior blepharitis. After the initial VKG, a meticulous cleaning of the lids with a mild alkali shampoo (10% Johnson's baby shampoo in sterile water) was done, first by gently scrubbing the closed eyelid fissure with the solution to mobilize and emulsify any Meibomian gland secretions followed by cleaning of the upper and lower margins individually, using Q-tip applicators soaked in the detergent. Three patients with tear film lipid layer excess (TFLE), which correlated with the presence of a superior or central corneal steepening in VKG, were studied. In two of the subjects, careful lid washing reversed either completely or partially this VKG effect, whereas in the last patient the VKG changes after artificially increasing the tear film lipid content is described. Meibomian gland lipid secretions may induce mainly superior and occasionally central VKG corneal steepening that is not correlated with any slit-lamp pathologic findings. Computerized corneal topography can help detect such corneal abnormalities, and their reversibility may distinguish them from other pathologic conditions (such as contact lens-induced warpage, eccentric ablations, irregular astigmatism, superior keratoconus).

Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

PubMed

Kam, Wendy R; Liu, Yang; Ding, Juan; Sullivan, David A

2016-08-01

Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival.

Effects of a New Eyelid Shampoo on Lid Hygiene and Eyelash Length in Patients with Meibomian Gland Dysfunction: A Comparative Open Study.

PubMed

Kobayashi, Asuka; Ide, Takeshi; Fukumoto, Teruki; Miki, Emiko; Tsubota, Kazuo; Toda, Ikuko

2016-01-01

Purpose . Meibomian gland dysfunction (MGD) can lead to abnormalities in the composition and function of tear film, resulting in dry eye. Eyelid hygiene is a key to management of MGD. We tested a novel eyelid shampoo (Eye Shampoo Long, ESL) for its ability to maintain lid hygiene. This shampoo is nonirritating and can potentially lengthen eyelashes. This study was aimed to evaluate the efficacy of ESL in the treatment of MGD and its effects on eyelash length. Methods . Ten patients with MGD and 10 healthy subjects without MGD applied ESL twice daily for 8 weeks. Patients were examined for lid margin and dry eye before and after the trial. Subjective symptoms were evaluated. Eyelash length was measured at baseline and at the end of the trial. Results . In the MGD group, significant improvements were observed in subjective symptoms obstruction of the meibomian orifice, secretion of meibum, eyelashes contamination, eyelid margin foam, and SPK. Eyelash length became significantly longer. Conclusions . Maintaining eyelid hygiene using ESL improved the eyelid margins and symptoms of dry eye in MGD patients and increased eyelash length. These findings are promising and warrant confirmation in a larger randomized controlled study.

Effects of a New Eyelid Shampoo on Lid Hygiene and Eyelash Length in Patients with Meibomian Gland Dysfunction: A Comparative Open Study

PubMed Central

Miki, Emiko

2016-01-01

Purpose. Meibomian gland dysfunction (MGD) can lead to abnormalities in the composition and function of tear film, resulting in dry eye. Eyelid hygiene is a key to management of MGD. We tested a novel eyelid shampoo (Eye Shampoo Long, ESL) for its ability to maintain lid hygiene. This shampoo is nonirritating and can potentially lengthen eyelashes. This study was aimed to evaluate the efficacy of ESL in the treatment of MGD and its effects on eyelash length. Methods. Ten patients with MGD and 10 healthy subjects without MGD applied ESL twice daily for 8 weeks. Patients were examined for lid margin and dry eye before and after the trial. Subjective symptoms were evaluated. Eyelash length was measured at baseline and at the end of the trial. Results. In the MGD group, significant improvements were observed in subjective symptoms obstruction of the meibomian orifice, secretion of meibum, eyelashes contamination, eyelid margin foam, and SPK. Eyelash length became significantly longer. Conclusions. Maintaining eyelid hygiene using ESL improved the eyelid margins and symptoms of dry eye in MGD patients and increased eyelash length. These findings are promising and warrant confirmation in a larger randomized controlled study. PMID:28078136

Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

PubMed Central

Kam, Wendy R.; Liu, Yang; Ding, Juan; Sullivan, David A.

2016-01-01

Purpose Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Methods Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Results Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Conclusions Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival. PMID:27552406

In vivo Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Dry Eye Patients with Different Symptoms.

PubMed

Zhao, Hui; Chen, Jing-Yao; Wang, Yu-Qian; Lin, Zhi-Rong; Wang, Shen

2016-11-05

Dry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM. A total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P< 0.05. In the severe symptom group, OSDI and SEEQ scores were significantly higher (P< 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P> 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P< 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild;P< 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P< 0.05). IVCM application provides a strong support to differentiate dry eye patients with different symptoms

On the prescribing of oral doxycycline or minocycline by UK optometrists as part of management of chronic Meibomian Gland Dysfunction (MGD).

PubMed

Doughty, Michael J

2016-02-01

To review the special pharmacology of tetracycline antibiotics as anti-inflammatory drugs for treatment of obstructive Meibomian gland disease (MGD) METHODS: PubMed was used as principal resource for articles, regardless of language, on doxycycline and minocycline with key interests being on their serum and tissue pharmacokinetics and their use in clinical studies as part of management of MGD. With oral dosing of between 50 and 200mg, peak blood levels of these antibiotics have been reported to be predictably dose-dependent at between 1 and 5 microgram/mL, with human tear film levels not being detectable with 100mg dosing of doxycycline but levels of 0.2 microgram/mL with 200mg minocycline. That these two tetracycline antibiotics reach the conjunctiva is indicated by conjunctival pigmentary changes due to photosensitization after very long term use. Based the reported use in a range of clinical studies on MGD, dosing with these two antibiotics for MGD is likely to be useful at relatively low doses (e.g. 100mg for doxycycline or 50mg for minocycline, either at once or twice daily depending on severity at presentation and previous history) continued for 2 to 3 months, with the expected outcome being small-to-substantial decreases in abnormal appearance of the glands (from -4 to -89%) and increases in tear film stability (from 21 to 273%). Oral doxycycline and minocycline have predictable pharmacokinetics and have been reported to improve Meibomian gland dysfunction over a few months of use. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction.

PubMed

Liu, Ruixing; Rong, Bei; Tu, Ping; Tang, Yun; Song, Wenjing; Toyos, Rolando; Toyos, Melissa; Yan, Xiaoming

2017-11-01

To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. Randomized, double-masked, controlled study. Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm 2 ) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm 2 . Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment. All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Immunohistochemical localization of fatty acid transporters and MCT1 in the sebaceous glands of mouse skin.

PubMed

Zheng, Miao; Lee, Shinhye; Tsuzuki, Satoshi; Inoue, Kazuo; Masuda, Daisaku; Yamashita, Shizuya; Iwanaga, Toshihiko

2016-01-01

The sebaceous glands secrete sebum to protect the epidermis and hairs by the oily products. The glands express several transporters and binding proteins for the production of fatty acids and uptake of their sources. The present immunohistochemical study examined the expression and localization of CD36, MCT1, FATP4, and E-FABP in the sebaceous glands, including the meibomian and preputial glands of mice. CD36 and MCT1 in sebaceous glands were largely co-localized along the plasma membrane of secretory cells, while they were separately expressed in the glandular portion of meibomian and preputial glands. Immunoreactivities for FATP4 and E-FABP appeared diffusely in the cytoplasm of secretory cells. Genetic deletion of CD36 did not affect the immunolocalization of the three other molecules. The sebaceous glands were judged to be useful for analyzing the functions and relation of fatty acid transporters and binding proteins.

Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

PubMed

Hagen, Kerry B; Bedi, Raman; Blackie, Caroline A; Christenson-Akagi, Kellie J

2018-01-01

The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD). This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining. In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant ( p =0.262 and p =0.414, respectively). At 3 months, SPEED score was significantly better in the VTP group ( p <0.05); other parameters were comparable between the two groups. A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

PubMed Central

Qazi, Y; Kheirkhah, A; Blackie, C; Cruzat, A; Trinidad, M; Williams, C; Korb, D R; Hamrah, P

2015-01-01

Purpose The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. Methods A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. Results Despite clinical improvement (TBUT: 6.4±1.2 s to 10.1±2.1 s, P=0.03; MGYLS: 3.5±0.8 glands to 7.0±1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6±110.1 cells/mm2; untreated MGD EIC=522.6±104.7 cells/mm2, P=0.69; responsive MGD EIC=194.9±119.4 cells/mm2, P<0.01; normals EIC=123.7±19.2 cells/mm2, P< 0.001), but not the cornea (refractory MGD DC=60.9±28.3 cells/mm2; normals DC=25.9±6.3 cells/mm2; P=0.43). EIC did not correlate with TBUT (Rs=−0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P<0.001) and TBUT (Rs=−0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen. Conclusion MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy. PMID:26088680

Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

PubMed

Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

2016-03-15

Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. © 2015 UICC.

Meibomian gland dysfunction and ocular discomfort in video display terminal workers.

PubMed

Fenga, C; Aragona, P; Cacciola, A; Spinella, R; Di Nola, C; Ferreri, F; Rania, L

2008-01-01

Meibomian gland dysfunction (MGD) is one of the most common ocular disorders encountered in clinical practice. The clinical manifestations of MGD are related to the changes in the tear film and ocular surface with symptoms of ocular discomfort. In recent years, many surveys have evaluated symptoms associated with the use of Video Display Terminals (VDT), and VDT use is recognized as a risk factor for eye discomfort. The aim of the present study was to determine if the presence of MGD contributes to the signs and symptoms of ocular discomfort during the use of VDT. In course of a routine health surveillance programme, a group of 70 subjects fulfilled the inclusion criteria and responded to a questionnaire about symptoms of ocular discomfort. The following ocular tests were performed: tear break-up time, fluorescein corneal stain, and basal tear secretion test. A total of 52 subjects out of 70 (74.3%) had MGD. A statistically significant correlation between the symptoms of ocular discomfort and hours spent on VDT work was observed in the total population (r=0.358; P=0.002; 95% CI 0.13-0.54) and in the group of subjects with MGD (r=0.365; P=0.009; 95% CI 0.103-0.58). Such correlation was not shown in subjects without MGD. The high prevalence of MGD among the subjects with symptoms of ocular discomfort suggests that this diagnosis should be considered when occupational health practitioners encounter ocular complaints among VDT operators. It appears that MGD can contribute to the development of ocular discomfort in VDT operators.

Investigation of antioxidant systems in human meibomian gland and conjunctival tissues.

PubMed

Nezzar, Hachemi; Mbekeani, Joyce N; Noblanc, Anais; Chiambaretta, Frédéric; Drevet, Joël R; Kocer, Ayhan

2017-12-01

Oxidative stress (OS) associated with direct contact with the environment and light exposure is a very potent and continuous stressor of the ocular surface and internal structures of the eye that are required to manage its effects. Constant replenishment of tears together with the superficial lipid layer produced by the meibomian glands (MG) is one protective mechanism. The lipid-rich fraction of the tears coats the deeper aqueous fraction, preventing its evaporation. However, lipids are particularly sensitive to oxidative damage that could alter tear film quality. To counteract oxidative damage, MG along with other structures of the ocular surface use primary antioxidant (AO) systems to limit OS damage such as lipid peroxidation. Limited information concerning the primary enzymatic AO system of the human MG prompted this investigation. Using different approaches (RT-PCR, enzymatic activity assays and immuno-fluorescent microscopy), we determined the presence, distribution and subcellular locations of the major AO enzymes belonging to the classical catalytic triad (superoxide dismutase, catalase and glutathione peroxidases) in adult human MG and conjunctiva (Conj). We showed that both tissues exhibit glutathione peroxidase expression. In addition to the ubiquitous cytosolic GPx1 protein, there was significant expression of GPx2, GPx4 and GPx7. These isoforms are known to preferentially scavenge phospholipid-hydroperoxide compounds. This characterization of the primary AO system of human MG and Conj may help pave the way for the development of diagnostic procedures and have implications for treatment of common MG dysfunction (MGD) and dry eye syndrome (DES). Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of duration of contact lens wear on the structure and function of the meibomian glands.

PubMed

Alghamdi, Waleed M; Markoulli, Maria; Holden, Brien A; Papas, Eric B

2016-03-01

To investigate the effects of the duration of contact lens (CL) wear on the meibomian glands (MGs), eyelid and tear film. This was a cross-sectional study of CL wearers and non-wearers (NWs) aged between 18 and 35 years. The sample comprised of: (i) Three groups of CL wearers of different duration profiles (short, moderate and long experience of CL wear); (ii) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months prior to the present study; (iii) healthy non-wearers as a control group. Study procedures were conducted in the order from least invasive to most invasive as follows: symptom assessment, lipid assessment, non-invasive break-up time, tear meniscus area, tear osmolarity and evaporation, Phenol red thread, MG expressibility, ocular surface and eyelid assessments, meibography, Marx line and lid wiper assessment using lissamine green. For statistical comparison of continuous data, one-way analysis of variance was used with Bonferroni post-hoc correction, where appropriate. Kruskal-Wallis test and Pearson Chi-Square respectively were used for ordinal and categorical variables. A total of 100 participants (49 males and 51 females; mean age ± SD: 25.4 ± 4.1) were enrolled across the five groups, such that each was composed of 20 age/sex matched individuals. Significant differences between the study groups were found for MG expressibility (p < 0.001), number of plugged orifices (p = 0.001), number of expressed orifices (p < 0.001), MG dropout (p = 0.001), Marx line score (p < 0.001), palpebral redness (p = 0.003), and roughness (p = 0.002), non-invasive break-up time (p < 0.001), Phenol red thread (p = 0.005), and tear meniscus area (p = 0.029). For all these variables, the NW group was statistically different from all other groups. Duration of wear was not a significant factor, except for Marx line score which was different in PWs compared to those with longer experience of CL wear (p = 0.03) CONCLUSION: Alterations to MG morphology and

Relationships Between Meibomian Gland Loss and Age, Sex, and Dry Eye.

PubMed

Pult, Heiko

2018-02-12

This study evaluated relationships between meibomian gland loss (MGL) and age, sex, and dry eye. Dry eye and MGL of the lower eyelid was evaluated from 112 randomly selected subjects (66 women; mean age 62.8; SD ±15.7; and age range: 19-89 years) from Horst Riede GmbH, Weinheim, Germany. In addition, subjects were grouped into dry eye and non-dry eye by the Ocular Surface Disease Index (OSDI) score, lid-parallel conjunctival folds and non-invasive break-up time. Symptoms were evaluated by the OSDI. Meibography of the lower eyelid was performed using a Cobra camera (bon Optic, Lübeck, Germany), and images were analyzed by its digital grading tool. Data were analyzed by backward, multiple regression analyses and Pearson correlation. Analyzing all subjects, multiple regression analyses detected that age and dry eye status (dry eye diagnosis or OSDI) but not sex were significantly related to MGL. In both, non-dry eye (n=66) and dry eye subjects (n=46), dry eye status (OSDI) but not age or sex was significantly related to MGL. Ocular Surface Disease Index scores were significantly correlated with MGL, but this correlation was stronger among all subjects (Pearson correlation; r=0.536, P<0.001) and dry eye group subjects (r=0.520, P<0.001) than in non-dry eye group subjects (r=0.275, P=0.014). Dry eye group subjects showed significantly increased MGL of the lower eyelid. Age and dry eye status were related to MGL of the lower eyelid, but sex was not; dry eye status was the dominant factor.

Antimicrobial role of human meibomian lipids at the ocular surface.

PubMed

Mudgil, Poonam

2014-10-14

Human meibomian lipids form the outermost lipid layer of the tear film and serve many important functions to maintain its integrity. Although not investigated earlier, these lipids may have antimicrobial properties that help in strengthening the innate host defense of tears at the ocular surface. The aim of this study was to investigate the antimicrobial role of human meibomian lipids. Ocular pathogenic bacteria, Staphylococcus aureus 31, Pseudomonas aeruginosa 19, Pseudomonas aeruginosa 20, and Serratia marcescens 35, were grown in the presence and absence of human meibomian lipids in an artificial tear solution at the physiological temperature. Viable counts were obtained to note the number of bacteria surviving the treatment with meibomian lipids. Bacterial cells were imaged using scanning electron microscopy to observe the damages caused by meibomian lipids. Viable count results showed that in the presence of meibomian lipids, growth of all bacteria was considerably lower. Scanning electron microscopy showed that meibomian lipids caused extensive cellular damage to bacteria as manifested in smaller size, loss of aggregation, abnormal phenotype, cellular distortion, damaged cell wall, and cell lysis. This is the first-ever report of the antimicrobial role of human meibomian lipids. These lipids possess antimicrobial properties against both Gram-positive and Gram-negative bacteria and are involved in the innate host defense of tears in protecting the ocular surface against microbial pathogens. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Investigations on the conjunctival goblet cells and the characteristics of the glands associated with the eye in chinchillas (Chinchilla Laniger).

PubMed

Voigt, Susanne; Fuchs-Baumgartinger, Andrea; Egerbacher, Monika; Tichy, Alexander; Nell, Barbara

2012-09-01

To investigate the density and distribution of conjunctival goblet cells (GC) and study the anatomy and microscopic characteristics of glands associated with the eye in chinchillas (Chinchilla Laniger). 12 chinchillas were included in the study. Conjunctiva (divided into four regions), eyelids, and glands were embedded in paraffin wax, sectioned, stained, and analyzed. Highest GC densities were found in the palpebral region of the nasal and temporal conjunctiva of both eyelids (GC index: 25.1-18.2%), and lowest densities, in the bulbar and marginal region of the nasal and temporal conjunctiva of both eyelids (GC index: 1.5-0.0%). Meibomian glands extend along the entire length of both eyelids, and the whole glandular complex broadens toward the temporal canthus. This is macroscopically visible through the conjunctiva. The openings of the Meibomian glands are macroscopically not discernible. The light pink, smooth, and crescent-shaped lacrimal gland lies next to the aforementioned broadened part of the Meibomian glands in the temporal canthus. The whitish, 0.9-cm-long, smooth Harderian gland is firmly attached to the posterior part of the globe and extends nasally from the optic nerve to the equator. Furthermore, chinchillas possess two lacrimal puncta, situated on the inner conjunctival surface of both eyelids near the medial canthus. A pigmented lacrimal canaliculus originates from each punctum. The vestigial nictitating membrane is supported by a hyaline cartilage and is pigmented at its free margin. Chinchillas possess a Harderian gland, a lacrimal gland, and Meibomian glands. The GC density in the nasal and temporal palpebral conjunctiva is higher than in guinea pigs. © 2012 American College of Veterinary Ophthalmologists.

Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

PubMed

Seifert, P; Spitznas, M

1999-06-01

This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the Severity of Dry Eye.

PubMed

Vu, Chi Hoang Viet; Kawashima, Motoko; Yamada, Masakazu; Suwaki, Kazuhisa; Uchino, Miki; Shigeyasu, Chika; Hiratsuka, Yoshimune; Yokoi, Norihiko; Tsubota, Kazuo

2018-02-16

To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED). Cross-sectional observational study. This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis. Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated. Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score. We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001). This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Longitudinal Changes in Tear Evaporation Rates After Eyelid Warming Therapies in Meibomian Gland Dysfunction.

PubMed

Yeo, Sharon; Tan, Jen Hong; Acharya, U Rajendra; Sudarshan, Vidya K; Tong, Louis

2016-04-01

Lid warming is the major treatment for meibomian gland dysfunction (MGD). The purpose of the study was to determine the longitudinal changes of tear evaporation after lid warming in patients with MGD. Ninety patients with MGD were enrolled from a dry eye clinic at Singapore National Eye Center in an interventional trial. Participants were treated with hot towel (n = 22), EyeGiene (n = 22), or Blephasteam (n = 22) twice daily or a single 12-minute session of Lipiflow (n = 24). Ocular surface infrared thermography was performed at baseline and 4 and 12 weeks after the treatment, and image features were extracted from the captured images. The baseline of conjunctival tear evaporation (TE) rate (n = 90) was 66.1 ± 21.1 W/min. The rates were not significantly different between sexes, ages, symptom severities, tear breakup times, Schirmer test, corneal fluorescein staining, or treatment groups. Using a general linear model (repeat measures), the conjunctival TE rate was reduced with time after treatment. A higher baseline evaporation rate (≥ 66 W/min) was associated with greater reduction of evaporation rate after treatment. Seven of 10 thermography features at baseline were predictive of reduction in irritative symptoms after treatment. Conjunctival TE rates can be effectively reduced by lid warming treatment in some MGD patients. Individual baseline thermography image features can be predictive of the response to lid warming therapy. For patients that do not have excessive TE, additional therapy, for example, anti-inflammatory therapy, may be required.

In vivo confocal microscopy of meibomian glands in primary blepharospasm

PubMed Central

Lin, Tong; Gong, Lan

2016-01-01

Abstract The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case–control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar

Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?

PubMed

Golebiowski, Blanka; Badarudin, Noor; Eden, John; You, Jingjing; Hampel, Ulrike; Stapleton, Fiona

2017-02-01

To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women. A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs. Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p<0.001, R 2 adj=0.75). Serum hormones were not significant predictors of ocular symptoms in multivariate analysis (p>0.05). Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Surfactant properties of human meibomian lipids.

PubMed

Mudgil, Poonam; Millar, Thomas J

2011-03-25

Human meibomian lipids are the major part of the lipid layer of the tear film. Their surfactant properties enable their spread across the aqueous layer and help maintain a stable tear film. The purpose of this study was to investigate surfactant properties of human meibomian lipids in vitro and to determine effects of different physical conditions such as temperature and increased osmolarity, such as occur in dry eye, on these properties. Human meibomian lipids were spread on an artificial tear solution in a Langmuir trough. The lipid films were compressed and expanded to record the surface pressure-area (Π-A) isocycles. The isocycles were recorded under different physical conditions such as high pressure, increasing concentration and size of divalent cations, increasing osmolarity, and varying temperature. Π-A isocycles of meibomian lipids showed that they form liquid films that are compressible and multilayered. The isocycles were unaffected by increasing concentration or size of divalent cations and increasing osmolarity in the subphase. Temperature had a marked effect on the lipids. Increase in temperature caused lipid films to become fluid, an expected feature, but decrease in temperature unexpectedly caused expansion of lipids and an increase in pressure suggesting enhanced surfactant properties. Human meibomian lipids form highly compressible, non-collapsible, multilayered liquid films. These lipids have surfactants that allow them to spread across an aqueous subphase. Their surfactant properties are unaffected by increasing divalent cations or hyperosmolarity but are sensitive to temperature. Cooling of meibomian lipids enhances their surfactant properties.

Meibomian Gland Dysfunction and Treatment (Posterior Blepharitis)

MedlinePlus

... if left untreated, MGD can cause or exacerbate dry eye symptoms and eyelid inflammation. The oil glands become ... in permanent changes in the tear film and dry eyes. Symptoms include: ... Stickiness/ Crustiness Watering ...

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

PubMed

Lee, Ling; Garrett, Qian; Flanagan, Judith L; Vaddavalli, Pravin K; Papas, Eric B

2016-12-19

To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

Toward an Animal Model of the Human Tear Film: Biochemical Comparison of the Mouse, Canine, Rabbit, and Human Meibomian Lipidomes

PubMed Central

Butovich, Igor A.; Lu, Hua; McMahon, Anne; Eule, J. Corinna

2012-01-01

Purpose. Secretions that are produced by meibomian glands (also known as meibum) are a major source of lipids for the ocular surface of humans and animals alike. Many animal species have been evaluated for their meibomian lipidomes. However, there have been a very small number of studies in which the animals were compared with humans side by side. Therefore, the purpose of this study was to compare meibum collected from humans and three typical laboratory animals, canines, mice, and rabbits, for their meibomian lipid composition in order to determine which animal species most resembles humans. Methods. High pressure liquid chromatography (HPLC) and gas-liquid chromatography (GLC) in combination with mass spectrometry were used to evaluate lipidomes of all tested species. Results. Among three tested animal species, mice were found to be the closest match to humans in terms of their meibomian lipidomes, while canines were the second closest species. The lipids of these three species were close to each other structurally and, for most lipid classes, quantitatively. The rabbit meibomian lipidome, on the other hand, was vastly different from lipidomes of all other tested species. Interestingly, a previously described class of lipids, acylated omega-hydroxy fatty acids (OAHFA), was found to be present in every tested species as the major amphiphilic component of meibum. Conclusions. Our side by side comparison of the rabbit and the human meibum demonstrated their vast differences. Thus, the rabbit seems to be a poor animal model of the human tear film, at least when studying its biochemistry and biophysics. PMID:22918629

Automated Measurement of Tear Film Dynamics and Lipid Layer Thickness for Assessment of Non-Sjögren Dry Eye Syndrome With Meibomian Gland Dysfunction.

PubMed

Ji, Yong Woo; Lee, Jeihoon; Lee, Hun; Seo, Kyoung Yul; Kim, Eung Kweon; Kim, Tae-Im

2017-02-01

To investigate automated values from an advanced corneal topographer with a built-in real keratometer, color camera, and ocular surface interferometer for the evaluation of non-Sjögren dry eye syndrome (NSDES) with meibomian gland dysfunction (MGD). Sixty-four patients (64 eyes) diagnosed with NSDES with MGD were enrolled. All eyes were evaluated using the Ocular Surface Disease Index (OSDI), fluorescence staining score, tear film breakup time (TBUT), Schirmer test, and MGD grade. Noninvasive Keratograph average tear film breakup time (NIKBUTav), tear meniscus height (TMHk), meibomian gland (MG) dropout grade, and lipid layer thickness (LLT) using interferometry were measured. Among automated indexes, NIKBUTav (mean 7.68 ± 4.07 s) and the MG dropout grade (mean 1.0 ± 0.5) significantly correlated with the OSDI (mean 40.6 ± 22.9) (r = -0.337, P = 0.006; and r = 0.201, P = 0.023, respectively), as did all conventional indicators, except the Schirmer score (mean 9.1 ± 5.9 mm). TMHk (mean 0.21 ± 0.18 mm) had significant correlation with the Schirmer score, the staining score (mean 1.2 ± 0.7), TBUT (mean 3.8 ± 1.8 s), and NIKBUTav (r = 0.298, P = 0.007; r = -0.268, P = 0.016; r = 0.459, P < 0.001; and r = 0.439, P < 0.001, respectively), but not any MGD indicator, even the MG dropout grade. NIKBUTav showed significant correlations with all clinical parameters and other automated values, except the Schirmer score and LLT (mean 83.94 ± 20.82 nm) (all (Equation is included in full-text article.)≥ 0.25 and P < 0.01). The MG dropout grade highly correlated with all indexes except TMHk (all (Equation is included in full-text article.)≥ 0.25 and P < 0.05). LLT was significantly associated with TBUT, MGD grade (mean 2.0 ± 0.7), and MG dropout grade (r = 0.219, P = 0.047; r = -0.221, P = 0.039; and r = 0.433, P < 0.001, respectively), although it was not related to patient symptoms. Automated noninvasive measurements using an advanced corneal topographer and LLT

In vitro effects of docosahexaenoic and eicosapentaenoic acid on human meibomian gland epithelial cells.

PubMed

Hampel, Ulrike; Krüger, Magret; Kunnen, Carolina; Garreis, Fabian; Willcox, Mark; Paulsen, Friedrich

2015-11-01

To investigate the effect of ω-3 fatty acids on human meibomian gland epithelial cells (HMGECs, cell line) in vitro. HMGECs were stimulated with docosahexaenoic acid (DHA) or combinations with eicosapentaenoic acid (EPA) and acetyl sialic acid (ASA). Sudan III fat staining, viability and proliferation assays, electric cell-substrate impedance sensing, real-time PCR for gene expression of cyclooxygenase-2 and 15-lipoxygenase and ELISAs for resolvin D1 (RvD1), IFNγ, TNFα and IL-6 were applied. Lipid droplet accumulation and viability was increased by 100 μM DHA in the presence or absence of EPA in serum cultured HMGECs. In contrast, HMGECs cultured with DHA and EPA under serum-free conditions showed minimal lipid accumulation, decreased proliferation and viability. Normalized impedance was significantly reduced in serum-free cultured HMGECs when stimulated with DHA and EPA. HMGECs cultured in serum containing medium showed increased normalized impedance under DHA and EPA stimulation compared to DHA or EPA alone or controls. IL-6 and IFNγ were downregulated in HMGECs treated for 72 h with DHA and EPA. In general, TNFα, IFNγ and IL-6 levels were decreased after 72 h compared to 24 h in serum containing medium with or without DHA or EPA. The concentration of RvD1 was elevated 2-fold after DHA treatment. Cyclooxygenase-2 gene expression decreased compared to controls during DHA stimulation after 72 h. Treatment with DHA and ASA revealed a decreased 15-lipoxygenase gene expression which was reduced after three days of DHA incubation. DHA and EPA supplementation affected HMGECs in vitro and supported anti-inflammatory effects by influencing cytokine levels, decreasing COX-2 expression and increasing the production of RvD1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adsorption of human tear lipocalin to human meibomian lipid films.

PubMed

Millar, Thomas J; Mudgil, Poonam; Butovich, Igor A; Palaniappan, Chendur K

2009-01-01

Tear lipocalin (Tlc) is a major lipid binding protein in tears and is thought to have an important role in stabilizing the Meibomian lipid layer by transferring lipids to it from the aqueous layer or ocular surface, or by adsorbing to it directly. These possible roles have been investigated in vitro using human Tlc. Tlc was purified from human tears by size exclusion chromatography followed by ion exchange chromatography. Three additional samples of the Tlc were prepared by lipidation, delipidation, and relipidation. The lipids extracted from the purified Tlc were analyzed by HPLC-MS followed by fragmentation. Adsorption of these different forms of Tlc to a human Meibomian lipid film spread on the surface of an artificial tear buffer in a Langmuir trough were observed by recording changes in the pressure with time (Pi-T profile) and monitoring the appearance of the film microscopically. These results were compared with similar experiments using a bovine Meibomian lipid film. The results indicated that Tlc binds slowly to a human Meibomian lipid film compared with lysozyme or lactoferrin, even at 37 degrees C. The adsorption of Tlc to a human Meibomian lipid film was very different from its adsorption to a bovine Meibomian lipid film, indicating the nature of the lipids in the film is critical to the adsorption process. Similarly, the different forms of Tlc had quite distinct adsorption patterns, as indicated both by changes in Pi-T profiles and the microscopic appearance of the films. It was concluded that human Tlc was capable of adsorbing to and penetrating into a Meibomian lipid layer, but this process is very complex and depends on both the types of lipids bound to Tlc and the lipid complement comprising the Meibomian lipid film.

Adsorption of Human Tear Lipocalin to Human Meibomian Lipid Films

PubMed Central

Millar, Thomas J.; Mudgil, Poonam; Butovich, Igor A.; Palaniappan, Chendur K.

2009-01-01

Purpose Tear lipocalin (Tlc) is a major lipid binding protein in tears and is thought to have an important role in stabilizing the Meibomian lipid layer by transferring lipids to it from the aqueous layer or ocular surface, or by adsorbing to it directly. These possible roles have been investigated in vitro using human Tlc. Methods Tlc was purified from human tears by size exclusion chromatography followed by ion exchange chromatography. Three additional samples of the Tlc were prepared by lipidation, delipidation, and relipidation. The lipids extracted from the purified Tlc were analyzed by HPLC-MS followed by fragmentation. Adsorption of these different forms of Tlc to a human Meibomian lipid film spread on the surface of an artificial tear buffer in a Langmuir trough were observed by recording changes in the pressure with time (∏-T profile) and monitoring the appearance of the film microscopically. These results were compared with similar experiments using a bovine Meibomian lipid film. Results The results indicated that Tlc binds slowly to a human Meibomian lipid film compared with lysozyme or lactoferrin, even at 37°C. The adsorption of Tlc to a human Meibomian lipid film was very different from its adsorption to a bovine Meibomian lipid film, indicating the nature of the lipids in the film is critical to the adsorption process. Similarly, the different forms of Tlc had quite distinct adsorption patterns, as indicated both by changes in ∏-T profiles and the microscopic appearance of the films. Conclusions It was concluded that human Tlc was capable of adsorbing to and penetrating into a Meibomian lipid layer, but this process is very complex and depends on both the types of lipids bound to Tlc and the lipid complement comprising the Meibomian lipid film. PMID:18757516

Risk factors for severe Meibomian gland atrophy in a young adult population: A cross-sectional study

PubMed Central

2017-01-01

Purpose Assess potential risk factors for severe Meibomian gland atrophy (SMGA) in a young adult population. Methods Cross-sectional study using medical history and ocular surface examination to evaluate relationships with study outcomes: SMGA, tear lipid layer (TLL) thickness, non-invasive (NITBUT) and fluorescein (FTBUT) tear breakup times, and symptoms using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Results One hundred one participants (101; 202 eyes; Age: mean±SD = 22.3±4.0 years) completed the study. Hormonal birth control (HBC) use was the only significant risk factor for SMGA (p = 0.028). Female HBC users had 4.8 times greater odds of having SMGA compared to female HBC non-users (p = 0.028), but the odds of having SMGA was similar between female HBC non-users and males (p = 0.885). Multivariable analysis suggested that the relationship between SMGA and TLL thickness was dependent on HBC use. Compared to female HBC non-users without SMGA, TLL thickness for HBC users was estimated to be 10 nm thinner if SMGA was absent (p = 0.007) and 21 nm thinner if SMGA was present (p<0.001). SMGA status had no significant impact on TLL thickness among female HBC non-users (p = 0.552). The effect of TLL thickness on FTBUT was small but significant (p = 0.026). TLL thickness was not significantly associated with NITBUT (p = 0.349). Neither FTBUT nor NITBUT was significantly associated with the SPEED score. Conclusion HBC use may be associated with SMGA, supporting the hypothesis that SMGA could lead to thinner TLL. However, less evidence was present to support that thin TLL could lead to clinically detectable tear film instability and subsequently to increased ocular dryness symptoms. Further investigation with a larger sample size is warranted to confirm these findings. PMID:28957399

Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America.

PubMed

Abreu-Velez, Ana Maria; Howard, Michael S; Hashimoto, Takashi; Grossniklaus, Hans E

2010-03-01

Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4', 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a substrate with 1 mmol/L of sodium

Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America

PubMed Central

Abreu-Velez, Ana Maria; Howard, Michael S.; Hashimoto, Takashi; Grossniklaus, Hans E.

2010-01-01

Background Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). Objective Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. Methods We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4′, 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). Results We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

PubMed

Stern, M E; Beuerman, R W; Fox, R I; Gao, J; Mircheff, A K; Pflugfelder, S C

1998-11-01

Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

The pineal gland from development to function.

PubMed

Sapède, Dora; Cau, Elise

2013-01-01

The pineal gland is a small neuroendocrine organ whose main and most conserved function is the nighttime secretion of melatonin. In lower vertebrates, the pineal gland is directly photosensitive. In contrast, in higher vertebrates, the direct photosensitivity of the pineal gland had been lost. Rather, the action of this gland as a relay between environmental light conditions and body functions involves reception of light information by the retina. In parallel to this sensory regression, the pineal gland (and its accessory organs) appears to have lost several functions in relation to light and temperature, which are important in lower vertebrate species. In humans, the functions of the pineal gland overlap with the functions of melatonin. They are extremely widespread and include general effects both on cell protection and on more precise functions, such as sleep and immunity. Recently, the role of melatonin has received a considerable amount of attention due to increased cancer risk in shift workers and the discovery that patients suffering from neurodegenerative diseases, autism, or depression exhibit abnormal melatonin rhythms. © 2013 Elsevier Inc. All rights reserved.

The effect of Meibomian lipids and tear proteins on evaporation rate under controlled in vitro conditions.

PubMed

Herok, George Henryk; Mudgil, Poonam; Millar, Thomas James

2009-07-01

The lipid layer of the tear film is associated with preventing evaporative loss. The ability of human Meibomian lipids to reduce evaporation in vitro was tested. Films of human or animal Meibomian lipids or mixtures of cholesterol and phosphatidylcholine were spread on the surface of either artificial buffer or on whole tears and placed on a mass balance that was enclosed in a sealed chamber. The temperature was adjusted to 37 degrees C and gas flow was controlled. Increasing the amounts of Meibomian lipids gave a very small reduction in evaporation. It was concluded from these in vitro experiments that prevention of evaporation from the tear film is not due to the Meibomian lipids alone, but is more likely to be due to a complex interaction between components of the aqueous and the Meibomian lipids.

Evaluation of the adhesive properties of the cornea by means of optical coherence tomography in patients with meibomian gland dysfunction and lacrimal tear deficiency.

PubMed

Napoli, Pietro Emanuele; Coronella, Franco; Satta, Giovanni Maria; Galantuomo, Maria Silvana; Fossarello, Maurizio

2014-01-01

The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders. Prospective, case-control study. Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants. An excellent (≥5 minutes), borderline (within 3-5 minutes), fair (within 1-3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001). ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome.

The role of the lacrimal functional unit in the pathophysiology of dry eye.

PubMed

Stern, Michael E; Gao, Jianping; Siemasko, Karyn F; Beuerman, Roger W; Pflugfelder, Stephen C

2004-03-01

The majority of dry eye symptoms are due to a chronic inflammation of the lacrimal functional unit resulting in a loss of tear film integrity and normal function. This leads to a reduction in the ability of the ocular surface to respond to environmental challenges. The underlying cause of tear film dysfunction is the alteration of tear aqueous, mucin, and lipid components. This may result from a systemic autoimmune disease or a local autoimmune event. A lack of systemic androgen support to the lacrimal gland has been shown to be a facilitative factor in the initiation of this type of pathophysiology. Tear secretion is controlled by the lacrimal functional unit consisting of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland and the interconnecting innervation. If any portion of this functional unit is compromised, lacrimal gland support to the ocular surface is impeded. Factors such as neurogenic inflammation and T cell involvement in the disease pathogenesis as well as newly developed animal models of ocular surface inflammation are discussed.

Real-world assessment of diquafosol in dry eye patients with risk factors such as contact lens, meibomian gland dysfunction, and conjunctivochalasis: subgroup analysis from a prospective observational study

PubMed Central

Yamaguchi, Masahiko; Nishijima, Takeshi; Shimazaki, Jun; Takamura, Etsuko; Yokoi, Norihiko; Watanabe, Hitoshi; Ohashi, Yuichi

2015-01-01

Purpose To evaluate the efficacy and safety of diquafosol (DQS) ophthalmic solution in dry eye (DE) patients wearing contact lenses (CLs) or with concomitant meibomian gland dysfunction (MGD) or conjunctivochalasis in a real-world setting. Patients and methods From a cohort of patients enrolled in a prospective observational study, DE patients who met the Japanese diagnostic criteria and who received DQS as a monotherapy were extracted and stratified according to the presence or absence of CL use, MGD, and conjunctivochalasis. Corneal and conjunctival fluorescein staining score, tear film break-up time, total symptom score (12 DE-related subjective symptoms), patient-reported outcomes, and adverse reactions were investigated. Results DQS treatment resulted in significant improvement in total symptom score, corneal and conjunctival fluorescein staining score, and tear film break-up time without significant differences between patient subgroups with versus without CL use, MGD, or conjunctivochalasis. Comparable proportions of patients perceived symptomatic improvements in all subgroups. There were no adverse reactions specifically associated with the CL use or any comorbidity of MGD or conjunctivochalasis. Conclusion DQS can be used effectively and safely as a monotherapy for the treatment of DE patients wearing CLs or with concomitant MGD or conjunctivochalasis. PMID:26664039

Adsorption of apo- and holo-tear lipocalin to a bovine Meibomian lipid film.

PubMed

Mudgil, Poonam; Millar, Thomas J

2008-04-01

Adsorption of apo- and holo-tear lipocalin (Tlc) to bovine Meibomian lipid film was studied. A Langmuir trough was used for these studies and the adsorption of protein was observed by recording changes in the pressure with time (pi-T profile). The films were photographed at different stages of adsorption by doping Meibomian lipids with a fluorescently tagged lipid. The results indicated that apo-Tlc adsorbed much more quickly than holo-Tlc to the Meibomian lipid film. Contrary to the expectation that holo-Tlc would release lipids to the surface and surface pressure would be higher, it was found that the surface pressure was higher with the adsorption of apo-Tlc to the surface. Photography of the films showed that apo- and holo-Tlc interacted differently with the Meibomian lipid layer. Adsorption of holo-Tlc resulted in big bright patches and adsorption of apo-Tlc resulted in many small patches along with the big patches. Both forms of Tlc produced a more stable film as indicated by decreased movement of the protein adsorbed films, and a higher maximum surface pressure upon compression of these films compared with Meibomian lipid films alone. Isocyles of apo-Tlc adsorbed films gave a higher surface pressure than that of holo-Tlc. From these results, it is concluded that both apo- and holo-Tlc adsorbed to the Meibomian lipid layer and the delivery of the lipids from Tlc to the outer lipid layer could not be detected by our techniques. Its scavenging role to remove lipids from the corneal surface and bind with them might be beneficial for increasing tear viscosity but whether those lipids are delivered to the outermost lipid layer still remains unclear.

The Aging Lacrimal Gland: Changes in Structure and Function

PubMed Central

Rocha, Eduardo M.; Alves, Monica; Rios, J. David; Dartt, Darlene A.

2014-01-01

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed. PMID:18827949

The aging lacrimal gland: changes in structure and function.

PubMed

Rocha, Eduardo M; Alves, Monica; Rios, J David; Dartt, Darlene A

2008-10-01

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

Adsorption of lysozyme to phospholipid and meibomian lipid monolayer films.

PubMed

Mudgil, Poonam; Torres, Margaux; Millar, Thomas J

2006-03-15

It is believed that a lipid layer forms the outer layer of the pre-ocular tear film and this layer helps maintain tear film stability by lowering its surface tension. Proteins of the aqueous layer of the tear film (beneath the lipid layer) may also contribute to reducing surface tension by adsorbing to, or penetrating the lipid layer. The purpose of this study was to compare the penetration of lysozyme, a tear protein, into films of meibomian lipids and phospholipids held at different surface pressures to determine if lysozyme were part of the surface layer of the tear film. Films of meibomian lipids or phospholipids were spread onto the surface of a buffered aqueous subphase. Films were compressed to particular pressures and lysozyme was injected into the subphase. Changes in surface pressure were monitored to determine adsorption or penetration of lysozyme into the surface film. Lysozyme penetrated a meibomian lipid film at all pressures tested (max=20 mN/m). It also penetrated phosphatidylglycerol, phosphatidylserine or phosphatidylethanolamine lipid films up to a pressure of 20 mN/m. It was not able to penetrate a phosphatidylcholine film at pressures >or=10 mN/m irrespective of the temperature being at 20 or 37 degrees C. However, it was able to penetrate it at very low pressures (<10 mN/m). Epifluorescence microscopy showed that the protein either adsorbs to or penetrates the lipid layer and the pattern of mixing depended upon the lipid at the surface. These results indicate that lysozyme is present at the surface of the tear film where it contributes to decreasing the surface tension by adsorbing and penetrating the meibomian lipids. Thus it helps to stabilize the tear film.

EFFECT OF INFLAMMATION ON LACRIMAL GLAND FUNCTION

PubMed Central

Zoukhri, Driss

2005-01-01

The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sjögren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states. PMID:16309672

In vivo confocal microscopy of meibomian glands in primary blepharospasm: A prospective case-control study in a Chinese population.

PubMed

Lin, Tong; Gong, Lan

2016-06-01

The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case-control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

2013-01-01

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland. PMID:24084941

Radiotherapy Dose-Volume Effects on Salivary Gland Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

The surface activity of purified ocular mucin at the air-liquid interface and interactions with meibomian lipids.

PubMed

Millar, Thomas J; Tragoulias, Sophia T; Anderton, Philip J; Ball, Malcolm S; Miano, Fausto; Dennis, Gary R; Mudgil, Poonam

2006-01-01

Ocular mucins are thought to contribute to the stability of the tear film by reducing surface tension. The purpose of this study was to compare the effect of different mucins and hyaluronic acid (HA) alone and mixed with meibomian lipids on the surface pressure at an air-liquid interface. A Langmuir trough and Wilhelmy balance were used to measure and compare the surface activity of bovine submaxillary gland mucin (BSM), purified BSM, purified bovine ocular mucin and HA, and mixtures of these with meibomian lipids, phosphatidylcholine, and phosphatidylglycerol. Their appearance at the surface of an air-buffer interface was examined using epifluorescence microscopy. Purified ocular mucin had no surface activity even at concentrations that were 100 times more than normally occur in tears. By contrast, commercial BSM caused changes to surface pressure that were concentration dependent. The surface pressure-area profiles showed surface activity with maximum surface pressures of 12.3-22.5 mN/m depending on the concentration. Purified BSM showed no surface activity at low concentrations, whereas higher concentrations reached a maximum surface pressure of 25 mN/m. HA showed no surface activity, at low or high concentrations. Epifluorescence showed that the mucins were located at the air-buffer interface and changed the appearance of lipid films. Purified bovine ocular mucin and HA have no surface activity. However, despite having no surface activity in their own right, ocular mucins are likely to be present at the surface of the tear film, where they cause an increase in surface pressure by causing a compression of the lipids (a reorganization of the lipids) and alter the viscoelastic properties at the surface.

[Efficacy of physiotherapy and hygienic procedures in treatment of adults and children with chronic blepharitis and dry eye syndrome].

PubMed

Prozornaia, L P; Brzhevskiĭ, V V

2013-01-01

110 patients aged from 3 to 42 years old were examined to estimate the efficacy of chronic blepharitis treatment: 50 patients with chronic blepharitis and dry eye syndrome (DES), 28 with DES due to computer vision syndrome and 32 with isolated chronic blepharitis. All patients received eyelid massage. If the secretion was too thick and difficult to evacuate from meibomian glands then duct probing was performed. In addition a complex of hygienic procedures was performed using phytoproducts ("Geltec-Medika", Russia): blepharoshampoo, blepharolotion, blepharogel 1 and 2. Moist warm pads (with blepharolotion and calendula extraction) were applied on the eyelids in 25 patients. Massage and probing of meibomian gland ducts and hygienic procedures were showed to be effective in management of clinical signs of chronic blepharitis including coexisting DES. Moist warm pads improve efficacy of background therapy in patients with meibomian gland hypofunction and have no effect in blepharitis with excessive meibomian gland secretion. Eyelid hygiene was showed to be effective in adults and children as well including infants.

The spectrum of STAT functions in mammary gland development

PubMed Central

Hughes, Katherine; Watson, Christine J.

2012-01-01

The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

PubMed

Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2016-04-01

Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Neuronal and hormonal regulatory mechanisms of tears production and secretion].

PubMed

Mrugacz, Małgorzata; Zywalewska, Nella; Bakunowicz-Lazarczyk, Alina

2005-01-01

The ocular surface, tear film, lacrimal glands act as a functional unit to preserve the quality of the refractive surface of the eye, and to resist injury and protect the eye against bodily and environmental conditions. Homeostasis of this functional unit involves neuronal and hormonal regulatory mechanisms. The eye appears to be a target organ for sex hormones particulary the androgen, as they modulate the immune system and trophic functions of the lacrimal and Meibomian glands.

[Abnormal of tear lipid layer and recent advances in clinical study of dry eye].

PubMed

Xiao, Xin-Ye; Liu, Zu-Guo

2012-03-01

Dry eye is a common disease in the ophthalmological clinic, which is related to the dysfunction of tear film. The tear film is composed of lipid layer, aqueous layer and mucin layer (or lipid layer, aqueous/mucin layer). The lipid of the outmost layer derived from Meibomian gland and distributed on the tear film after blinking can decrease the evaporation and stabilize the tear film. The thickness, quality, and distribution of lipid layer are impaired in many dry eye patients, hence restoring the physiological function of lipid layer may be crucial for the treatment of this kind of dry eye. The lipid artificial tears manifest great effects on increasing lipid layer thickness, stabilizing tear film, improving Meibomian gland dysfunction, and promoting tear film distribution.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

PubMed

Nam, Kihoon; Maruyama, Christina L; Wang, Ching-Shuen; Trump, Bryan G; Lei, Pedro; Andreadis, Stelios T; Baker, Olga J

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function

PubMed Central

Nam, Kihoon; Maruyama, Christina L.; Wang, Ching-Shuen; Trump, Bryan G.; Lei, Pedro; Andreadis, Stelios T.

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration. PMID:29095857

Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Limesand, Kirsten H., E-mail: limesank@u.arizona.ed; Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Avila, Jennifer L.

Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVBmore » mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.« less

Salivary Gland NK Cells Are Phenotypically and Functionally Unique

PubMed Central

Brossay, Laurent

2011-01-01

Natural killer (NK) cells and CD8+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or Treg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells. PMID:21249177

Effects of Aging in Dry Eye

PubMed Central

de Paiva, Cintia S.

2017-01-01

Dry eye affects millions of people worldwide and causes eye well recognized risk factors for dry eye. Anatomical and inflammation-induced age-related changes affect all components of the lacrimal gland functional unit, inclusive of lacrimal gland, conjunctiva, meibomian gland and compromise ocular surface health. There is increased evidence that inflammation plays a role in dry eye. This review will summarize the current knowledge about aging and dry eye, inclusive of lessons learned from animal models and promising therapies. PMID:28282314

Establishment of Functional Acinar-like Cultures from Human Salivary Glands

PubMed Central

Jang, S.I.; Ong, H.L.; Gallo, A.; Liu, X.; Illei, G.

2015-01-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers—namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. PMID:25416669

Establishment of functional acinar-like cultures from human salivary glands.

PubMed

Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

2015-02-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. © International & American Associations for Dental Research 2014.

Uterine glands: development, function and experimental model systems

PubMed Central

Cooke, Paul S.; Spencer, Thomas E.; Bartol, Frank F.; Hayashi, Kanako

2013-01-01

Development of uterine glands (adenogenesis) in mammals typically begins during the early post-natal period and involves budding of nascent glands from the luminal epithelium and extensive cell proliferation in these structures as they grow into the surrounding stroma, elongate and mature. Uterine glands are essential for pregnancy, as demonstrated by the infertility that results from inhibiting the development of these glands through gene mutation or epigenetic strategies. Several genes, including forkhead box A2, beta-catenin and members of the Wnt and Hox gene families, are implicated in uterine gland development. Progestins inhibit uterine epithelial proliferation, and this has been employed as a strategy to develop a model in which progestin treatment of ewes for 8 weeks from birth produces infertile adults lacking uterine glands. More recently, mouse models have been developed in which neonatal progestin treatment was used to permanently inhibit adenogenesis and adult fertility. These studies revealed a narrow and well-defined window in which progestin treatments induced permanent infertility by impairing neonatal gland development and establishing endometrial changes that result in implantation defects. These model systems are being utilized to better understand the molecular mechanisms underlying uterine adenogenesis and endometrial function. The ability of neonatal progestin treatment in sheep and mice to produce infertility suggests that an approach of this kind may provide a contraceptive strategy with application in other species. Recent studies have defined the temporal patterns of adenogenesis in uteri of neonatal and juvenile dogs and work is underway to determine whether neonatal progestin or other steroid hormone treatments might be a viable contraceptive approach in this species. PMID:23619340

[Functional morphology of the submandibular salivary glands of white rats during aging involution].

PubMed

Rybakova, M G

1979-12-01

Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

Functional salivary gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Ogawa, Miho; Oshima, Masamitsu; Imamura, Aya; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Nakajima, Kei; Hirayama, Masatoshi; Tachikawa, Tetsuhiko; Tsuji, Takashi

2013-01-01

Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren’s syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia. PMID:24084982

[Structuro-functional units of the salivary and lacrimal glands].

PubMed

Kostilenko, Iu P; Mysliuk, I V; Deviatkin, E A

1986-09-01

By means of the multilayer graphic and plastic reconstruction methods using series of semithin sections, spatial tridimensional organization of the epithelial complexes and blood microcirculatory bed in the rat palatal salivary glands and the lacrimal gland of the human newborn have been studied. Since their ducts serve not only for discharging their secrete into the external medium, but also for accumulation (as collectors), the sublobular unit--adenomere should be referred to as a part of elementary level of organization of the epithelial complexes. The adenomere has in its composition a collecting centrally situating duct. However, while studying structure of the blood microcirculatory bed, it is found out that there is not any strict territorial correspondence between its functional units and structural units of the glandular epithelium. Nevertheless, giving a great importance to a tight syntopic connection of the collecting ducts of the adenomeres with the postcapillary venules (that belong to filtrating microvessels), these are sublobular units--adenomeres that are distinguished as structural-functional units in the glands.

[Evaluation of salivary gland function in women with autoimmune thyroid diseases].

PubMed

Koczor-Rozmus, Aleksandra; Zwirska-Korczala, Krystyna; Sadlak-Nowicka, Jadwiga; Ilewicz, Leşzek; Mayer-Parka, Danuta; Wierucka-Młynarczyk, Beata

2003-01-01

The function of the salivary glands is regulated by nervous system which influences salivary circulation. Moreover the volume of secreted saliva depends on the humoral agents, including thyroid hormones. The aim of the study was to determine the quantity of the secreted mixed resting and stimulated saliva in women with autoimmune thyroid diseases (AITD) depending on the function of the thyroid gland (hyperthyroidism, hypothyroidism and euthyroidism). The association between thyroid antibody concentrations (TPO-Ab, Tg-Ab, TR-Ab) and volume of secreted saliva was also examined. Studies were performed in 106 women suffering from AITD and 15 healthy volunteers. In hyperthyroid women there was a decrease in volumes of resting (57.14%) and stimulated (89.29%) saliva. Similarly, a decrease in secretion of resting (75%) and stimulated (66.67%) saliva was shown in hypothyroid women. In euthyroid patients with AITD there was a partial normalisation of salivary glands function. The negative correlation between concentrations of TPO-Ab, Tg-Ab and the volume of resting and stimulated saliva was found. In conclusion, AITD may be associated with disturbances in salivary secretion which depends on thyroid hormones production. It can be suggested that autoimmunological processes within salivary glands may influence their function.

Bioprinting of a functional vascularized mouse thyroid gland construct.

PubMed

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Diffusion-Weighted Magnetic Resonance Imaging to Evaluate Major Salivary Gland Function Before and After Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dirix, Piet; Keyzer, Frederik de; Vandecaveye, Vincent

2008-08-01

Purpose: To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC). Methods and Materials: DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy. Results: Before RT, the mean ADC value at rest was significantly lower in the parotidmore » than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy. Conclusions: Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.« less

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

PubMed Central

Hill, Grace; Headon, Denis; Harris, Zoey I.; Huttner, Kenneth; Limesand, Kirsten H.

2014-01-01

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170

Identification of factors that function in Drosophila salivary gland cell death during development using proteomics

PubMed Central

McPhee, C K; Balgley, B M; Nelson, C; Hill, J H; Batlevi, Y; Fang, X; Lee, C S; Baehrecke, E H

2013-01-01

Proteasome inhibitors induce cell death and are used in cancer therapy, but little is known about the relationship between proteasome impairment and cell death under normal physiological conditions. Here, we investigate the relationship between proteasome function and larval salivary gland cell death during development in Drosophila. Drosophila larval salivary gland cells undergo synchronized programmed cell death requiring both caspases and autophagy (Atg) genes during development. Here, we show that ubiquitin proteasome system (UPS) function is reduced during normal salivary gland cell death, and that ectopic proteasome impairment in salivary gland cells leads to early DNA fragmentation and salivary gland condensation in vivo. Shotgun proteomic analyses of purified dying salivary glands identified the UPS as the top category of proteins enriched, suggesting a possible compensatory induction of these factors to maintain proteolysis during cell death. We compared the proteome following ectopic proteasome impairment to the proteome during developmental cell death in salivary gland cells. Proteins that were enriched in both populations of cells were screened for their function in salivary gland degradation using RNAi knockdown. We identified several factors, including trol, a novel gene CG11880, and the cop9 signalsome component cop9 signalsome 6, as required for Drosophila larval salivary gland degradation. PMID:22935612

[Comparative ultrastructural study of parotid gland, lacrimal gland and pituitary gland between miniature pig and mouse].

PubMed

Yan, Xing; Hai, Bo; Sun, Yi-lin; Zhang, Chun-mei; Wang, Song-ling

2009-02-01

To study the ultrastructure of parotid glands, lacrimal glands and pituitary glands between miniature pig and mouse. Five adult miniature pigs and 5 mice were studied. Ultrastructure of their parotid glands, lacrimal glands, and pituitary glands was observed. The secretary granules in acinar cell of miniature pig parotid glands showed higher density and more aequalis than those of mice. The cell apparatus in acinar cell of mouse parotid glands were more plentiful than those of miniature pigs. The secretary granules on blood vessel wall were richer in parotid gland of miniature pigs compared with mouse parotid gland. Lacrimal gland had the similar ultrastructure to parotid gland in these two animals. Many blood vessel antrum were found in pituitary glands of these two animals. Compared with mouse parotid glands, there are more secretary granules in acinar cells and vascular endothelial cells in miniature pig parotid glands, which might enter blood stream and have function of endocrine secretion.

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roesink, Judith M.; Schipper, Maria; Busschers, Wim

2005-11-15

Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion ofmore » radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.« less

Hedgehog signaling: endocrine gland development and function.

PubMed

Cohen, M Michael

2010-01-01

The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

PubMed

Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

2010-01-01

Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

PubMed

Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

[Factors influencing the measurement of tear film lipid layer thickness with interferometry].

PubMed

Finis, D; Pischel, N; Borrelli, M; Schrader, S; Geerling, G

2014-06-01

The quantitative measurement of the tear film lipid layer thickness is a relatively new and promising method. However, so far it has not been investigated whether there is a diurnal or a day to day variability and whether certain factors are confounding the measurement of the lipid layer thickness. In three different experimental settings, 10 subjects without known sicca syndrome were examined at three different time points on one day, on three different days and before and after therapeutic expression of the Meibomian glands. As a comparison, the parameters tear film break-up time, tear meniscus height, diagnostic expression of the Meibomian glands and subjective symptoms, determined using the OSDI (ocular surface disease index) questionnaire, were measured. The results of the study showed a smaller variation of the lipid layer thickness measurements during the day and from day to day compared to the tear film break-up time. The expression of the Meibomian glands significantly increased the lipid layer thickness. There was a correlation between the baseline values of tear film break-up time and the lipid layer thickness. Our data showed that the lipid layer thickness as measured with the Lipiview® interferometer appears to be a relatively constant parameter over time. In addition, the expression of the Meibomian glands could be identified as a potential confounding factor. In this study we included only healthy subjects without known sicca syndrome. For the future our findings need to be validated in dry eye patients. Georg Thieme Verlag KG Stuttgart · New York.

Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis

PubMed Central

Charchaflie, R. J.; Fernandez, L. Bustos; Perec, C. J.; Gonzalez, E.; Marzi, A.

1974-01-01

Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested. PMID:4852110

Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

PubMed

Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2013-11-01

Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

PubMed Central

Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B), β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands. PMID:29464184

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Immunohistochemical sweat gland profiles.

PubMed

Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

2013-09-01

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

LASIK and dry eye.

PubMed

Toda, Ikuko

2007-01-01

Dry eye is one of the most common complications after laser-assisted in situ keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer test, reduced corneal sensitivity, and decreased functional visual acuity. The symptoms and signs last at least 1 month after LASIK. Although the mechanisms for developing post-LASIK dry eye are not completely understood, loss of corneal innervation by flap-making may affect the reflex loops of the corneal-lacrimal gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian gland, resulting in decreased aqueous and lipid tear secretion and mucin expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms and signs than first surgery, it is suggested that other factors rather than loss of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye. The treatments of dry eye include artificial tears, topical cyclosporine, hot compress, punctal plugs, and autologous serum eye drops. For patients with severe preoperative dry eye, a combination of punctal plugs and serum eye drops is required to be used before surgery.

Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-01-01

parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

Impact of selective pituitary gland incision or resection on hormonal function after adenoma or cyst resection.

PubMed

Barkhoudarian, Garni; Cutler, Aaron R; Yost, Sam; Lobo, Bjorn; Eisenberg, Amalia; Kelly, Daniel F

2015-12-01

With the resection of pituitary lesions, the anterior pituitary gland often obstructs transsphenoidal access to the lesion. In such cases, a gland incision and/or partial gland resection may be required to obtain adequate exposure. We investigate this technique and determine the associated risk of post-operative hypopituitarism. All patients who underwent surgical resection of a pituitary adenoma or Rathke cleft cyst (RCC) between July 2007 and January 2013 were analyzed for pre- and post-operative hormone function. The cohort of patients with gland incision/resection were compared to a case-matched control cohort of pituitary surgery patients. Total hypophysectomy patients were excluded from outcome analysis. Of 372 operations over this period, an anterior pituitary gland incision or partial gland resection was performed in 79 cases (21.2 %). These include 53 gland incisions, 12 partial hemi-hypophysectomies and 14 resections of thinned/attenuated anterior gland. Diagnoses included 64 adenomas and 15 RCCs. New permanent hypopituitarism occurred in three patients (3.8 %), including permanent DI (3) and growth hormone deficiency (1). There was no significant difference in the rate of worsening gland dysfunction nor gain of function. Compared to a control cohort, there was a significantly lower incidence of transient DI (1.25 vs. 11.1 %, p = 0.009) but no significant difference in permanent DI (3.8 vs. 4.0 %) in the gland incision group. Selective gland incisions and gland resections were performed in over 20 % of our cases. This technique appears to minimize traction on compressed normal pituitary gland during removal of large lesions and facilitates better visualization and removal of cysts, microadenomas and macroadenomas.

The Rapalogue, CCI-779, improves salivary gland function following radiation.

PubMed

Morgan-Bathke, Maria; Harris, Zoey I; Arnett, Deborah G; Klein, Rob R; Burd, Randy; Ann, David K; Limesand, Kirsten H

2014-01-01

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side

Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PubMed Central

Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

2012-01-01

Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

The epigenetic landscape of mammary gland development and functional differentiation

USDA-ARS?s Scientific Manuscript database

Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600

Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dijkema, Tim, E-mail: T.Dijkema@umcutrecht.n; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.

2010-10-01

Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: Amore » total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.« less

Function of the parotid gland in juvenile recurrent parotitis: a case series.

PubMed

Xie, Li-song; Pu, Yi-ping; Zheng, Ling-yan; Yu, Chuang-qi; Wang, Zhi-jun; Shi, Huan

2016-04-01

Our aim was to find out how the parotid gland functions in 44 patients with juvenile recurrent parotitis, and to assess the value of measuring the serum amylase activity. Clinical and personal details were recorded, and all patients had their serum amylase activity measured together with sialography during the chronic phase. The function of the gland was classified by sialographic images. The chi square test and Spearman's rank correlation coefficient were used in the statistical analyses. There was a significant association between the degree of glandular function and serum amylase activity (p=0.014). The patients with unilateral and bilateral disease differed significantly in their degree of glandular function (p=0.020), those with bilateral disease having poorer function. There were no significant correlations between other clinical variables and glandular function. Serum amylase activity is an important diagnostic variable in juvenile recurrent parotitis, and poor parotid function reflects the severity of the disease. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Functional differences in the acinar cells of the murine major salivary glands.

PubMed

Kondo, Y; Nakamoto, T; Jaramillo, Y; Choi, S; Catalan, M A; Melvin, J E

2015-05-01

In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl(-)-dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca(2+)] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl(-) efflux and the protein levels of the Ca(2+)-activated Cl(-) channel TMEM16A, the major apical Cl(-) efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na(+)-K(+)-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl(-) uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl(-) movement, including the transporter activities of the Cl(-) uptake and efflux pathways, and intracellular Ca(2+) mobilization. © International & American Associations for Dental Research 2015.

HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

EPA Science Inventory

Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

Abstract
The studies review...

The clypeal gland: a new exocrine gland in termite imagoes (Isoptera: Serritermitidae, Rhinotermitidae, Termitidae).

PubMed

Křížková, Barbora; Bourguignon, Thomas; Vytisková, Blahoslava; Sobotník, Jan

2014-11-01

Social insects possess a rich set of exocrine organs producing diverse pheromones and defensive compounds. This is especially true for termite imagoes, which are equipped with several glands producing, among others, sex pheromones and defensive compounds protecting imagoes during the dispersal flight and colony foundation. Here, we describe the clypeal gland, a new termite exocrine organ occurring in the labro-clypeal region of imagoes of most Rhinotermitidae, Serritermitidae and Termitidae species. The clypeal gland of Coptotermes testaceus consists of class 1 (modified epidermal cell) and class 3 (bicellular gland unit) secretory cells. Ultrastructural features suggest that the gland secretes volatile compounds and proteins, probably after starting the reproduction. One peculiar feature of the gland is the presence of multiple secretory canals in a single canal cell, a feature never observed before in other insect glands. Although the function of the gland remains unknown, we hypothesize that it could produce secretion signalling the presence of functional reproductives or their need to be fed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wax-tear and meibum protein, wax–β-carotene interactions in vitro using infrared spectroscopy

PubMed Central

Faheem, Samad; Kim, Sung-Hye; Nguyen, Jonathan; Neravetla, Shantanu; Ball, Matthew; Foulks, Gary N; Yappert, Marta C; Borchman, Douglas

2012-01-01

Protein–meibum and terpenoids–meibum lipid interactions could be important in the etiology of meibomian gland dysfunction (MGD) and dry eye symptoms. In the current model studies, attenuated total reflectance (ATR) infrared (IR) spectroscopy was used to determine if the terpenoid β-carotene and the major proteins in tears and meibum affect the hydrocarbon chain conformation and carbonyl environment of wax, an abundant component of meibum. The main finding of these studies is that mucin binding to wax disordered slightly the conformation of the hydrocarbon chains of wax and caused the wax carbonyls to become hydrogen bonded or experience a more hydrophilic environment. Lysozyme and lactoglobulin, two proteins shown to bind to monolayers of meibum, did not have such an effect. Keratin and β-carotene did not affect the fluidity (viscosity) or environment of the carbonyl moieties of wax. Based on these results, tetraterpenoids are not likely to influence the structure of meibum in the meibomian glands. In addition, these findings suggest that it is unlikely that keratin blocks meibomian glands by causing the meibum to become more viscous. Among the tear fluid proteins studied, mucin is the most likely to influence the conformation and carbonyl environment of meibum at the tear film surface. PMID:22564968

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

PubMed

Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

2016-11-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development.

PubMed

Redman, R S

2008-06-01

Radiation therapy for cancer of the head and neck can devastate the salivary glands and partially devitalize the mandible and maxilla. As a result, saliva production is drastically reduced and its quality adversely altered. Without diligent home and professional care, the teeth are subject to rapid destruction by caries, necessitating extractions with attendant high risk of necrosis of the supporting bone. Innovative techniques in delivery of radiation therapy and administration of drugs that selectively protect normal tissues can reduce significantly the radiation effects on salivary glands. Nonetheless, many patients still suffer severe oral dryness. I review here the functional morphology and development of salivary glands as these relate to approaches to preventing and restoring radiation-induced loss of salivary function. The acinar cells are responsible for most of the fluid and organic material in saliva, while the larger ducts influence the inorganic content. A central theme of this review is the extent to which the several types of epithelial cells in salivary glands may be pluripotential and the circumstances that may influence their ability to replace cells that have been lost or functionally inactivated due to the effects of radiation. The evidence suggests that the highly differentiated cells of the acini and large ducts of mature glands can replace themselves except when the respective pools of available cells are greatly diminished via apoptosis or necrosis owing to severely stressful events. Under the latter circumstances, relatively undifferentiated cells in the intercalated ducts proliferate and redifferentiate as may be required to replenish the depleted pools. It is likely that some, if not many, acinar cells may de-differentiate into intercalated duct-like cells and thus add to the pool of progenitor cells in such situations. If the stress is heavy doses of radiation, however, the result is not only the death of acinar cells, but also a marked

Leg tendon glands in male bumblebees ( Bombus terrestris): structure, secretion chemistry, and possible functions

NASA Astrophysics Data System (ADS)

Jarau, Stefan; Žáček, Petr; Šobotník, Jan; Vrkoslav, Vladimír; Hadravová, Romana; Coppée, Audrey; Vašíčková, Soňa; Jiroš, Pavel; Valterová, Irena

2012-12-01

Among the large number of exocrine glands described in bees, the tarsal glands were thought to be the source of footprint scent marks. However, recent studies showed that the compounds used for marking by stingless bees are secreted by leg tendon instead of tarsal glands. Here, we report on the structure of leg tendon glands in males of Bombus terrestris, together with a description of the chemical composition of their secretions and respective changes of both during the males' lives. The ultrastructure of leg tendon glands shows that the secretory cells are located in three independent regions, separated from each other by unmodified epidermal cells: in the femur, tibia, and basitarsus. Due to the common site of secretion release, the organ is considered a single secretory gland. The secretion of the leg tendon glands of B. terrestris males differs in its composition from those of workers and queens, in particular by (1) having larger proportions of compounds with longer chain lengths, which we identified as wax esters; and (2) by the lack of certain hydrocarbons (especially long chain dienes). Other differences consist in the distribution of double bond positions in the unsaturated hydrocarbons that are predominantly located at position 9 in males but distributed at seven to nine different positions in the female castes. Double bond positions may change chemical and physical properties of a molecule, which can be recognized by the insects and, thus, may serve to convey specific information. The function of male-specific compounds identified from their tendon glands remains elusive, but several possibilities are discussed.

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function

PubMed Central

Concepcion, Axel R.; Vaeth, Martin; Wagner, Larry E.; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P.; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E.; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S.; Cuk, Mario; Yule, David I.

2016-01-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release–activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel–deficient patients and mice with ectodermal tissue–specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice. PMID:27721237

Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

PubMed

Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

2015-10-01

Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radioprotective Effect of Lidocaine on Function and Ultrastructure of Salivary Glands Receiving Fractionated Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hakim, Samer George, E-mail: samer.hakim@mkg-chir.mu-luebeck.de; Benedek, Geza Attila; Su Yuxiong

2012-03-15

Purpose: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. Methods and Materials: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary glandmore » function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. Results: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. Conclusions: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands.« less

One man's poison is another man's meat: using azithromycin-induced phospholipidosis to promote ocular surface health.

PubMed

Liu, Yang; Kam, Wendy R; Ding, Juan; Sullivan, David A

2014-06-05

Drug-induced phospholipidosis (PLD) is a common adverse effect which has led to the termination of clinical trials for many candidate pharmaceuticals. However, this lipid-inducing effect may be beneficial in the treatment of meibomian gland dysfunction (MGD). MGD is the major cause of dry eye disease (DED), which affects 40 million people in the USA and has no cure. Azithromycin (AZM) is a PLD-inducing antibiotic that is used off-label to treat MGD, and is presumably effective because it suppresses the MGD-associated conjunctival inflammation (i.e. posterior blepharitis) and growth of lid bacteria. We hypothesize that AZM can act directly to promote the function of human meibomian gland epithelial cells by inducing PLD in these cells, characterized by the accumulation of lipids and lysosomes. Immortalized human meibomian gland epithelial cells (HMGEC) were cultured with or without azithromycin for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy, TEM). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes. Many of these vesicles appeared to be lamellar bodies by TEM, which is the characteristic of PLD. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGECimmortalized. Our results support our hypothesis and confirm the beneficial effect of PLD induced by AZM on HMGEC. Our discovery reveals a new potential use of PLD-inducing drugs, and makes this adverse effect a beneficial effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

NASA Astrophysics Data System (ADS)

Pradhan, Swati

Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

Functional morphology of femoral glands in the Tegu lizard, Tupinambis merianae.

PubMed

Chamut, Silvia; Valdez, Valeria García; Manes, Mario E

2009-04-01

Several lizards have femoral glands, which have an influence in various reproductive behaviors. In this paper we describe the morphological organization of the femoral glands in the Tegu, Tupinambis merianae, by means of light and electron microscopy. Even though these glands are present in both genders, secretions during the reproductive period can only be found in males. The glandular parenchyma, which is organized in numerous secretory units, consists of keratinocyte-like cells and granular cells. The holocrine secretion is constituted from both cells, which lose their integrity and become a semi-amorphous material, reinforced by keratin sheets. The discharges of each unit merge together into a solid cylinder of secretion, surrounded by epithelial cells, that is extruded to the exterior. The keratin sheets and epithelial layers that surround both the complete and partial secretions form a sort of structural support suitable for the type of territorial demarcation characteristic of the species. The granular cells, supposedly the producers of pheromones, are characterized by the presence of electron-dense granules and multilaminar membranous bodies that show ultrastructural changes of unknown function. The free granules in the secretion cylinder may act as pheromone deposits.

[Morphofunctional and molecular bases of pineal gland aging].

PubMed

Khavinson, V Kh; Lin'kova, N S

2012-01-01

The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

Is the eccrine gland an integral, functionally important component of the human scalp pilosebaceous unit?

PubMed

Poblet, Enrique; Jiménez-Acosta, Francisco; Hardman, Jonathan A; Escario, Eduardo; Paus, Ralf

2016-02-01

The pilosebaceous unit (PSU) and the eccrine sweat gland (ESG) are classically described as completely independent skin appendages. However, careful inspection of scalp follicular units reveals that the secretory segment of the ESG spatially approximates the hair follicle in a position below the sebaceous gland and the insertion of the arrector pili muscle. Therefore, we propose here that, contrary to conventional wisdom, the PSU and the ESG should not be viewed in isolation, and may form instead, along with the arrector pili muscle and the apocrine gland (where present),one functional unit. For this, we suggest the more inclusive term of 'Hair Cluster' (HC). If confirmed, e.g. by 3D imaging techniques, the novel concept of a functional HC, whose individual components may communicate via secreted molecules and may share selected progenitor cell populations for HC repair/regeneration, has major physiological and pathological implications, which are briefly discussed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland

PubMed Central

Caricato, Roberto; Giordano, M. Elena; Schettino, Trifone; Lionetto, M. Giulia

2018-01-01

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation. PMID:29670538

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation.

PubMed

Marmary, Yitzhak; Adar, Revital; Gaska, Svetlana; Wygoda, Annette; Maly, Alexander; Cohen, Jonathan; Eliashar, Ron; Mizrachi, Lina; Orfaig-Geva, Carmit; Baum, Bruce J; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H

2016-03-01

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. ©2016 American Association for Cancer Research.

A novel organotypic 3D sweat gland model with physiological functionality

PubMed Central

Grüdl, Sabine; Banowski, Bernhard; Giesen, Melanie; Sättler, Andrea; Proksch, Peter; Welss, Thomas; Förster, Thomas

2017-01-01

Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers. To resemble the in vivo situation as close as possible, we applied the hanging drop cultivation technology regaining most of the markers when cultured in its natural spherical environment. To compare the organotypic 3D sweat gland model versus human sweat glands in vivo, we compared markers relevant for the eccrine sweat gland using transcriptomic and proteomic analysis. Comparing the marker profile, a high in vitro-in vivo correlation was shown. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), muscarinic acetylcholine receptor M3 (CHRM3), Na+-K+-Cl- cotransporter 1 (NKCC1), calcium-activated chloride channel anoctamin-1 (ANO1/TMEM16A), and aquaporin-5 (AQP5) are found at significant expression levels in the 3D model. Moreover, cholinergic stimulation with acetylcholine or pilocarpine leads to calcium influx monitored in a calcium flux assay. Cholinergic stimulation cannot be achieved with the sweat gland cell line NCL-SG3 used as a sweat gland model system. Our results show clear benefits of the organotypic 3D sweat gland model versus 2D cultures in terms of the expression of essential eccrine sweat gland key regulators and in the physiological response to stimulation. Taken together, this novel organotypic 3D sweat gland model shows a good in vitro-in vivo correlation and is an appropriate alternative for screening of potential bioactives

76 FR 51876 - Medical Devices; Ophthalmic Devices; Classification of the Eyelid Thermal Pulsation System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... meibomian gland dysfunction (MGD), also known as evaporative dry eye or lipid deficiency dry eye. The system... evaporative dry eye or lipid deficiency dry eye. The system consists of a component that is inserted around...

A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

PubMed

Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

2015-01-01

The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

PubMed Central

Zhu, Xiaoyan; Tollkuhn, Jessica; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary Although SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion. PMID:26651607

Mammary Gland Development

PubMed Central

Macias, Hector

2012-01-01

The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial/mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development – pubertal growth, pregnancy, lactation and involution – occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone and estrogen, as well as IGF1, to create a ductal tree that fills the fat pad. Upon pregnancy the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its pre-pregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. PMID:22844349

Bioengineered Lacrimal Gland Organ Regeneration in Vivo

PubMed Central

Hirayama, Masatoshi; Tsubota, Kazuo; Tsuji, Takashi

2015-01-01

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID:26264034

Gene Expression in Human Accessory Lacrimal Glands of Wolfring

PubMed Central

Ubels, John L.; Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Van Dyken, Rachel E.; Hatton, Mark P.

2012-01-01

Purpose. The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Methods. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Results. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. Conclusions. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs. PMID:22956620

Infantile bilateral glaucoma in a child with ectodermal dysplasia.

PubMed

Callea, Michele; Vinciguerra, Agatino; Willoughby, Colin E; Deroma, Laura; Clarich, Gabriella

2013-01-01

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

PubMed Central

Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations. PMID:24069265

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

PubMed

Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations.

Characterization of human pineal gland proteome.

PubMed

Yelamanchi, Soujanya D; Kumar, Manish; Madugundu, Anil K; Gopalakrishnan, Lathika; Dey, Gourav; Chavan, Sandip; Sathe, Gajanan; Mathur, Premendu P; Gowda, Harsha; Mahadevan, Anita; Shankar, Susarla K; Prasad, T S Keshava

2016-11-15

The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time. Interestingly, 1136 proteins from the human pineal gland were found to contain a signal peptide domain, which indicates the secretory nature of these proteins. An unbiased global proteomic profile of this biomedically important organ should benefit molecular research to unravel the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luijk, Peter van; Faber, Hette; Schippers, Jacobus M.

2009-07-15

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) ofmore » both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.« less

Salivation induced better lacrimal gland function in dry eyes.

PubMed

Pramanik, T; Ghising, R

2009-12-01

The dry eye syndrome is a common eye symptom causing blurry vision. To meet the demand of the modem world students and professionals are compelled to expose themselves to the computer screen for long stretch of time, which is one of the causes of dry eye. It is not always feasible to instil eyes with artificial tears time to time to protect them from dryness. Rather to adopt any simple physiological process associated with optimum lacrimation is a better option to keep eyes moist during computer works. Volunteers (n = 22) having mild dry eyes participated in this study. Tear production was assessed by Schirmer test by keeping Schirmer strip on ocular surface for 5 minutes and recording the length of the moistened area. Then the subject was allowed to keep a piece of lopsy candy (a sour fruit pulp mixed with sugar that is sweet and sour in taste) in mouth for 5 minutes that caused salivation. During salivation, again tear production was assessed. [It was standardized in such a way that, the length of the moistened strip will be 25 - 30 mm for normal eyes, 15 - 10 mm for dry eye, 06 - 10 mm for mild dry eye, 02 - 05 mm for moderate dryness and 00 - 01 mm for severe dry eye.] Tear production was found to be increased significantly (supported by increased length of moistened area of Schirmer strip) during salivation especially in dry eye in all volunteers. The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins; secretion of which are under tight neural control. Anticholinergic agents play an important role in ocular dryness because of hypo-secretion. The sensory root of facial nucleus contains efferent preganglionic parasympathetic fibers for submandibular and sublingual salivary gland and lacrimal gland. The sensory root conveys gustatory fibers from the presulcul area (anterior two-third) of the tongue via the chorda tympani and via the palatine and greater petrosal nerve, taste fibers from

Pheromones and exocrine glands in Isoptera.

PubMed

Costa-Leonardo, Ana Maria; Haifig, Ives

2010-01-01

Termites are eusocial insects that have a peculiar and intriguing system of communication using pheromones. The termite pheromones are composed of a blend of chemical substances and they coordinate different social interactions or activities, including foraging, building, mating, defense, and nestmate recognition. Some of these sociochemicals are volatile, spreading in the air, and others are contact pheromones, which are transmitted by trophallaxis and grooming. Among the termite semiochemicals, the most known are alarm, trail, sex pheromones, and hydrocarbons responsible for the recognition of nestmates. The sources of the pheromones are exocrine glands located all over the termite body. The principal exocrine structures considered pheromone-producing glands in Isoptera are the frontal, mandibular, salivary or labial, sternal, and tergal glands. The frontal gland is the source of alarm pheromone and defensive chemicals, but the mandibular secretions have been little studied and their function is not well established in Isoptera. The secretion of salivary glands involves numerous chemical compounds, some of them without pheromonal function. The worker saliva contains a phagostimulating pheromone and probably a building pheromone, while the salivary reservoir of some soldiers contains defensive chemicals. The sternal gland is the only source of trail-following pheromone, whereas sex pheromones are secreted by two glandular sources, the sternal and tergal glands. To date, the termite semiochemicals have indicated that few molecules are involved in their chemical communication, that is, the same compound may be secreted by different glands, different castes and species, and for different functions, depending on the concentration. In addition to the pheromonal parsimony, recent studies also indicate the occurrence of a synergic effect among the compounds involved in the chemical communication of Isoptera. Copyright © 2010 Elsevier Inc. All rights reserved.

Molecular characterization and functional significance of the Vti family of SNARE proteins in tick salivary glands

PubMed Central

Villarreal, Ashley M.; Adamson, Steven W.; Browning, Rebecca E.; Khem Raj, B.C.; Sajid, Muhammad Sohail; Karim, Shahid

2013-01-01

Exocytosis involves membrane fusion between secretory vesicles and the plasma membrane. The Soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs) and their receptor proteins (SNAREs) interact to fuse vesicles with the membrane and trigger the release of their sialosecretome out of the tick salivary gland cells. In this study, we examined the functional significance of the Vti family of SNARE proteins of blood-feeding Amblyomma maculatum and A. americanum. Vti1A and Vti1B have been implicated in multiple functional roles in vesicle transport. QRT-PCR studies demonstrated that the highest transcriptional expression of vti1a and vti1b genes occurs in unfed salivary glands, suggesting that elevated secretory vesicle formation occurs prior to feeding but continues at low rates after blood feeding commences. Vti1A and Vti1B localize to the secretory vesicles in unfed tick salivary glands in immunofluorescence microscopy studies. Knockdown of vti1a and vti1b by RNA interference resulted in a significant decrease in the engorged tick weight compared to the control during prolonged blood-feeding on the host. RNA interference of vti1a or vti1b impaired oviposition and none of the ticks produced eggs masses. Surprisingly, the double knockdown did not produce a strong phenotype and ticks fed normally on the host and produced egg masses, suggesting a compensatory mechanism exists within the secretory system which may have been activated in the double knockdown. These results suggest an important functional role of the Vti family of SNARE proteins in tick blood feeding and ultimately oviposition. Understanding the basic functions of the Vti family of SNARE proteins in salivary glands may lead to better ways to prevent tick attachment and transmission of tick-borne diseases. PMID:23499931

Repressor of Estrogen Receptor Activity (REA) Is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice

PubMed Central

Park, Sunghee; Zhao, Yuechao; Yoon, Sangyeon; Xu, Jianming; Liao, Lan; Lydon, John; DeMayo, Franco; O'Malley, Bert W.

2011-01-01

Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland. PMID:21862609

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

Morphology and function of lacrimal gland acinar cells in primary culture.

PubMed

Hann, L E; Tatro, J B; Sullivan, D A

1989-01-01

The objectives of the current investigation were fourfold: (1) to establish an effective procedure for the isolation of acinar cells from the rat lacrimal gland; (2) to evaluate the functional capacity of freshly isolated cells; (3) to determine defined culture conditions which permit maintenance of viable, differentiated cells, as well as secretory component (SC) production, during long-term culture; and (4) to characterize the morphological features of cultured cells. Acinar cells were isolated by serial incubation of gland fragments in chelating and enzymatic solutions, followed by centrifugation through a Ficoll gradient. The yield of viable cells/gland appeared to be age-dependent: cell recovery was inversely proportional to the age of the animals. Immunofluorescence analysis of freshly isolated cells showed the presence of SC, the IgA antibody receptor, within isolated cells. In addition, experiments with a labeled analog (Nle4-D-Phe7-alpha MSH) of alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrated specific binding sites on freshly isolated cells; alpha-MSH is a known modulator of acinar protein secretion. Maximum binding of the alpha-MSH analog occurred within 30 min, was dependent upon cell density and was reduced by coincubation with unlabeled alpha-MSH. To determine the culture requirements of acinar cells, cells were cultured on a variety of substrates (plastic or modified plastic [Primaria], coated with or without extracellular matrix [Matrigel]) in the presence or absence of various supplements and/or fetal calf serum (FCS) for 0.7 to 3.5 weeks. Cell attachment, function and long-term viability required an extracellular matrix. Moreover, in long term cultures (25 days), acinar cell attachment was enhanced by the inclusion of supplements to media containing 10% FCS. Replacement of serum with fibroblast growth factor, high-density lipoprotein and an increased concentration of epidermal growth factor resulted in a distinct "cobblestone

Dry Eye

MedlinePlus

... the Meibomian glands. Autoimmune disorders such as Sjögren’s syndrome, lupus, scleroderma, and rheumatoid arthritis and other disorders such as diabetes, thyroid disorders, and Vitamin A deficiency are associated with dry eye. Women are more likely to develop dry eye. ...

Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function.

PubMed

Stewart, Cassandra R; Obi, Nneka; Epane, Elodie C; Akbari, Alexander A; Halpern, Leslie; Southerland, Janet H; Gangula, Pandu R

2016-06-01

Xerostomia is defined as dry mouth resulting from a change in the amount or composition of saliva and is often a major oral health complication associated with diabetes mellitus (DM). Studies have shown that xerostomia is more common in females at the onset of DM. Evidence suggests that nitric oxide (NO) plays a critical role in healthy salivary gland function. However, the specific mechanisms by which NO regulates salivary gland function at the onset of DM have yet to be determined. This study has two aims: 1) to determine whether protein expression or dimerization of NO synthase enzymes (neuronal [nNOS] and endothelial [eNOS]) are altered in the onset of diabetic xerostomia; and 2) to determine whether the changes in nNOS/eNOS protein expression or dimerization are correlated with changes in NO cofactor tetrahydrobiopterin (BH4) biosynthetic enzymes (guanosine triphosphate cyclohydrolase-1 and dihydrofolate reductase). Functional and Western blot studies were performed in streptozotocin-induced and control Sprague-Dawley female rats with DM (type 1 [t1DM]) using standardized protocols. Confirmation of xerostomia was determined by increased water intake and decreased salivary flow rate. The results showed that in female rats with DM, salivary hypofunction is correlated with decreased submandibular and parotid gland sizes. The results also show a decrease in NOS and BH4 biosynthetic enzyme in submandibular glands. These results indicate that a decrease in submandibular NO-BH4 protein expression may provide insight pertaining to mechanisms for the development of hyposalivation in DM-induced xerostomia. Furthermore, understanding the role of the NO-BH4 pathway may give insight into possible treatment options for the patient with DM experiencing xerostomia.

[Aging of the pineal gland].

PubMed

Khavinson, V Kh; Golubev, A G

2002-01-01

The age-related changes in the pineal gland are functional rather than organic, which makes their correction or prevention more tenable. The amelioration or inhibition of some age-related impairments of the pineal gland were observed with dietary restriction and the use of S-adenosylmethionine or MAO-A inhibitors. A threefold increase in nocturnal melatonin peaks occurs in old rhesus monkeys treated with a synthetic peptide Ala-Glu-Asp-Gly (Epithalon) designed basing on the amino acid content of a pineal peptide extract Epithalamin. Other effects of Epithalon markedly overlap with melatonin effects. Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland.

[Effect of emotional-algesic stress on the hormonal function of thyroid and parathyroid glands].

PubMed

Kuripka, V I; Belokon', L E; Iakushev, V S

1989-01-01

Experiments on 215 Wistar rats have revealed that the state of the endured stress is an essential factor inducing disturbance in functioning of the hypothalamus-adenohypophysis-thyroid gland system accompanied by disturbance in regulation of the thyrotropin and triiodothyronine formation under conditions of myocardium necrosis development.

Analysis of Factors Associated With the Tear Film Lipid Layer Thickness in Normal Eyes and Patients With Dry Eye Syndrome.

PubMed

Jung, Ji Won; Park, Si Yoon; Kim, Jin Sun; Kim, Eung Kweon; Seo, Kyoung Yul; Kim, Tae-Im

2016-08-01

To determine the effects of clinical variables, including age, sex, history of refractive or cataract surgery, contact lens use, and ocular surface and meibomian gland parameters on the lipid layer thickness (LLT) in normal subjects and patients with dry eye syndrome (DES). A total of 64 normal subjects and 326 patients with DES were enrolled, and they underwent measurements of LLT with a LipiView interferometer and tear meniscus height using optical coherence tomography, tear film break-up time (TBUT) determination, ocular surface staining, Schirmer's test, examination of the lid margins and meibomian glands, and assessment using the Ocular Surface Disease Index (OSDI). In normal subjects, the median (range) LLT was 67 (33-100) nm, and age was the only factor that was significantly associated with LLT (β = 0.678, P = 0.028). In patients with DES, the median (range) LLT was 84 (20-100) nm, and 79.0% of the participants fulfilled the diagnostic criteria for meibomian gland dysfunction (MGD). In a multivariate analysis, increased age and female sex were significantly related to increased LLT (β = 0.282, P = 0.005 and β = 11.493, P < 0.001), and hypersecretory MGD and lid margin inflammation were independently associated with increased LLT (β = 11.299, P = 0.001 and β = 12.747, P = 0.001). Lipid layer thickness measurements using a new interferometer are significantly affected by demographic factors such as age, sex, ocular surgical history, and MGD type. Therefore, all of these factors must be considered in the diagnosis of ocular surface diseases.

[The effect of emotional stressors on thyroid gland function].

PubMed

Pastukhov, N A

1975-01-01

Response of the normal and goiterous thyroid gland to the information on the forthcoming operation was studied in 12 patients with varicose veins of the lower limbs and in 67 patients with thyrotoxicosis; this was done by determination of protein-bound iodine (PBI). PBI proved to increase before the operation in both groups of the patients. Due to undesirable hyperfunction of the thyroid gland prior to the operation in thyrotoxicosis, the psychodepressive premedication component should be increased.

How to promote and preserve eyelid health.

PubMed

Benitez-Del-Castillo, Jose M

2012-01-01

Disorders of the lacrimal functional unit are common in ophthalmological practice, with meibomian gland dysfunction, blepharitis, and dry eye forming a significant part of the general ophthalmologist's practice. The eyelid and its associated structures form a complex organ designed to protect the fragile corneal surface and improve visual acuity. This organ is subject to a number of disorders, including meibomian gland dysfunction, dry eye syndrome, anterior blepharitis, allergic and dermatological conditions, and disorders associated with contact lens use. Although commonly described separately, disorders of the lacrimal function unit are better considered as a group of interacting pathologies that have inflammatory mediators as a central feature. Eyelid hygiene, in the sense of routine cleansing and massage of the eyelids, is well accepted in the management of many disorders of the eyelid. However, a broader concept of eyelid health may be appropriate, in which eyelid cleansing is but a part of a more complete program of care that includes screening and risk assessment, patient education, and coaching. The ophthalmologist has an important role to play in helping patients persist with routine eyelid care that may be long-term or lifelong. A number of preparations exist to make routine eyelid care both more effective and more pleasant, and might also improve compliance. Several such preparations have been devised, and are being assessed in clinical studies, and appear to be effective and preferred by patients over traditional soap and water or baby shampoo.

Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

PubMed

Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-10-31

MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

A Prospective Study of Salivary Gland Function in Lymphoma Patients Receiving Head and Neck Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodrigues, Neesha A.; Killion, Leah; Hickey, Gail

2009-11-15

Purpose: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients with lymphoma receiving radiation therapy (RT) to the head and neck (H and N). Methods and Materials: We conducted a prospective study on salivary-gland function in lymphoma patients receiving RT to the H and N. Fifteen patients were enrolled on the study. Dose-volume histograms and mean doses to the salivary glands were generated. Radiation-related toxicities and H and N-specific QOL were assessed before treatment and at prespecified time points posttreatment. Factors predicting a decrement in QOL were explored using Fisher's exactmore » test. Results: During RT, 47% of patients experienced Grade >= 2 acute toxicity of the salivary gland, mucous membrane, or both. QOL scores improved over time, but up to one third of patients continued to have persistent oral symptoms at 2 years. At 6 months, a mean dose to at least one of the parotids of > 31 Gy was significantly associated with persistent dry mouth (100% vs. 17%, p = 0.02) and sticky saliva (100% vs. 25%, p = 0.04); a mean dose of > 11 Gy to the minor salivary glands was significantly associated with persistent sticky saliva (100% vs. 25%, p = 0.04), although the difference was no longer significant at 1 year. Conclusions: Limiting the mean parotid dose to <= 31 Gy and mean minor salivary gland dose to <= 11 Gy in lymphoma patients treated to the H and N may help reduce the risk of subacute xerostomia.« less

Making Plants Break a Sweat: the Structure, Function, and Evolution of Plant Salt Glands

PubMed Central

Dassanayake, Maheshi; Larkin, John C.

2017-01-01

Salt stress is a complex trait that poses a grand challenge in developing new crops better adapted to saline environments. Some plants, called recretohalophytes, that have naturally evolved to secrete excess salts through salt glands, offer an underexplored genetic resource for examining how plant development, anatomy, and physiology integrate to prevent excess salt from building up to toxic levels in plant tissue. In this review we examine the structure and evolution of salt glands, salt gland-specific gene expression, and the possibility that all salt glands have originated via evolutionary modifications of trichomes. Salt secretion via salt glands is found in more than 50 species in 14 angiosperm families distributed in caryophyllales, asterids, rosids, and grasses. The salt glands of these distantly related clades can be grouped into four structural classes. Although salt glands appear to have originated independently at least 12 times, they share convergently evolved features that facilitate salt compartmentalization and excretion. We review the structural diversity and evolution of salt glands, major transporters and proteins associated with salt transport and secretion in halophytes, salt gland relevant gene expression regulation, and the prospect for using new genomic and transcriptomic tools in combination with information from model organisms to better understand how salt glands contribute to salt tolerance. Finally, we consider the prospects for using this knowledge to engineer salt glands to increase salt tolerance in model species, and ultimately in crops. PMID:28400779

Lacritin and Other New Proteins of the Lacrimal Functional Unit

PubMed Central

McKown, Robert L.; Wang, Ningning; Raab, Ronald W.; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B.; Laurie, Gordon W.

2009-01-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction. PMID:18840430

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

McKown, Robert L; Wang, Ningning; Raab, Ronald W; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B; Laurie, Gordon W

2009-05-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

Update in Current Diagnostics and Therapeutics of Dry Eye Disease.

PubMed

Thulasi, Praneetha; Djalilian, Ali Reza

2017-11-01

Dry eye disease (DED) represents a heterogeneous group of conditions with tear film insufficiency and signs and/or symptoms of ocular surface irritation. The clinical manifestations of DED can be highly variable; hence the diagnosis is often based on a combination of symptoms, signs, and clinical tests, given that any one of these alone would miss a significant number of patients. Similarly, the treatment must often be tailored to each patient by targeting the specific mechanisms involved in his or her disease. The purpose of this review is to summarize recent advances that have allowed us to better recognize, categorize, and treat patients with DED. The most notable new diagnostic tests in DED are tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging. Therapeutically, anti-inflammatory therapy, meibomian gland heating and expression, and scleral contact lenses are some of the latest options available for treating DED. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Microvascular transplantation and replantation of the dog submandibular gland.

PubMed

Su, Wan Fu; Jen, Yee Min; Chen, Shyi Gen; Nieh, Shin; Wang, Chih-Hung

2006-05-01

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

[Serum thyroxine-binding protein for determining the functional state of the thyroid gland in pregnant women with endemic goiter].

PubMed

Korol'kova, O A; Cheremukhin, V I

1975-01-01

A determination was made of the hormone-forming capacity of the thyroid gland in pregnent women under conditions of goiter endemic at various periods of pregnancy by trimesters (123-in healthy pregnant women, 206-with euthyroid goiter of the I degree, 271-or II degree, 90-of the II degree, and 4-of the IV degree). A method of zonal electrophoresis in the medinal-veronal buffer was applied. Thyrofixin with I131 isotope (made in the USSR) was used. With increase of the periods of pregnancy and the degree of euthyroid hyperplasia of the thyroid gland and goiter the thyroid gland function became elevated irrespective of age.

Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.

PubMed

Tran, Simon D; Sugito, Takayuki; Dipasquale, Giovanni; Cotrim, Ana P; Bandyopadhyay, Bidhan C; Riddle, Kathryn; Mooney, David; Kok, Marc R; Chiorini, John A; Baum, Bruce J

2006-10-01

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

In Vivo Readout of CFTR Function: Ratiometric Measurement of CFTR-Dependent Secretion by Individual, Identifiable Human Sweat Glands

PubMed Central

Wine, Jeffrey J.; Char, Jessica E.; Chen, Jonathan; Cho, Hyung-ju; Dunn, Colleen; Frisbee, Eric; Joo, Nam Soo; Milla, Carlos; Modlin, Sara E.; Park, Il-Ho; Thomas, Ewart A. C.; Tran, Kim V.; Verma, Rohan; Wolfe, Marlene H.

2013-01-01

To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (∼50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a β-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ∼0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with ‘CFTR-related’ conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics. PMID:24204751

aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1.

PubMed

Chibly, Alejandro M; Wong, Wen Yu; Pier, Maricela; Cheng, Hongqiang; Mu, Yongxin; Chen, Ju; Ghosh, Sourav; Limesand, Kirsten H

2018-04-20

Xerostomia and salivary hypofunction often result as a consequence of radiation therapy for head and neck cancers, which are diagnosed in roughly 60,000 individuals every year in the U.S. Due to the lack of effective treatments for radiation-induced salivary hypofunction, stem cell-based therapies have been suggested to regenerate the irradiated salivary glands. Pharmacologically, restoration of salivary gland function has been accomplished in mice by administering IGF-1 shortly after radiation treatment, but it is not known if salivary stem and progenitor cells play a role. We show that radiation inactivates aPKCζ and promotes nuclear redistribution of Yap in a population of label-retaining cells in the acinar compartment of the parotid gland (PG)- which comprises a heterogeneous pool of salivary progenitors. Administration of IGF-1 post-radiation maintains activation of aPKCζ and partially rescues Yap's cellular localization in label retaining cells, while restoring salivary function. Finally, IGF-1 fails to restore saliva production in mice lacking aPKCζ, demonstrating the importance of the kinase as a potential therapeutic target.

Influence of interfacial rheology on stabilization of the tear film

NASA Astrophysics Data System (ADS)

Bhamla, M. Saad; Fuller, Gerald G.

2014-11-01

The tear film that protecting the ocular surface is a complex, thin film comprised of a collection of proteins and lipids that come together to provide a number of important functions. Of particular interest in this presentation is meibum, an insoluble layer that is spread from glands lining our eyelids. Past work has focussed on the role of this layer in reducing evaporation, although conflicting evidence on its ability to reduce evaporative loss has been published. We present here the beneficial effects that are derived through the interfacial viscoelasticity of the meibomian lipid film. This is a duplex film is comprised of a rich mixture of phospholipids, long chain fatty esters, and cholesterol esters. Using interfacial rheology measurements, meibum has been shown to be highly viscoelastic. By measuring the drainage and dewetting dynamics of thin aqueous films from hemispherical surfaces where those films are laden with insoluble layers of lipids at controlled surface pressure, we offer evidence that these layers strongly stabilize the films because of their ability to support surface shearing stresses. This alternative view of the role of meibum can help explain the origin of meibomian gland dysfunction, or dry eye disease, where improper compositions of this lipid mixture do not offer the proper mechanical resistance to breakage and dewetting of the tear film.

Models of cognitive functions with respect to selected parameters of functional state of the thyroid gland in post-menopausal women.

PubMed

Gujski, Mariusz; Pinkas, Jarosław; Witczak, Mariusz; Owoc, Alfred; Bojar, Iwona

2017-01-01

The objective of the study was the development of models of cognitive functions in a group of post-menopausal women, according to the concentration of the selected laboratory parameters evaluating the functional state of the thyroid gland. The study was conducted during 2012-2014, and covered women aged 50-65 years, minimum two years after the last menstruation, without chronic diseases, cancerous diseases, mental disorders, addiction to drugs or alcohol, and who did not use hormone replacement therapy. At the stage of qualification, a brief MoCA test was performed; 383 women were qualified for the study. Blood was collected for the determination of such parameters as: TSH, TT4, fT4, anti-TPO, anti-Tg, and AB-TSHR. Assessment of cognitive functions was performed using the diagnostic instrument Central Nervous System - Vital Signs (CNS-VS) (Polish version). The results were statistically analysed. The mean age of the women in the study was 56.4 ± 3.4; the mean TSH was 1.91 ± 1.35 mU/L, fT4 14.76 ± 2.34 pmol/L, and TT4 99.12 ± 16.98 nmol/L. Mean values were: 64.74 IU/L for anti-TPO, 100.69 IU/L for anti-Tg, and 1.40 IU/L for AB-TSHR. The examined women obtained the neurocognitive index (NCI) on the level of 84.4 scores, on average. The lowest results were obtained in tests assessing cognitive flexibility (mean 78.64 scores), processing speed (mean 79.25 scores), and executive functions (mean 79.75 scores). In the tests evaluating complex attention, the mean values were 82.24 scores, psychomotor speed - mean 83.42 scores, and reaction time - mean 86.87 scores. The women examined obtained the best results in tests assessing memory (mean 90.15 scores), including verbal (mean 91.22 scores), and visual (mean 93.37 scores). The NCI and cognitive function models were assessed from the aspect of thyroid gland examinations in post-menopausal women. Based on the analyses performed, the following conclusions were drawn: The developed models of cognitive functions indicate a

Biomacromolecule conjugated nanofiber scaffold for salivary gland tissue engineering

NASA Astrophysics Data System (ADS)

Jayarathanam, Kavitha

Xerostomia or dry mouth, resulting from loss of salivary gland secretion can be alleviated by tissue engineering approaches to restore glandular cell function. Engineering an artificial salivary gland structure requires closely mimicking the natural environment, both physically and functionally, to promote epithelial cell proliferation, monolayer formation and apico-basal polarization. While the physical structure of the salivary gland extracellular matrix (ECM) can be reconstructed using biocompatible nanofiber scaffolds, the chemical signals from ECM macromolecules are equally involved in the gland morphogenesis. In these glands, Hyaluronic acid (HA), a biomacromolecule that is a major component of the ECM, plays a crucial role in recruiting growth factors to improve cell viability and growth in these glands. Another molecule of interest that improved salivary epithelial cell viability and apico-basal differentiation is laminin, a major protein found in the basement membrane. We hypothesize that these biomacromolecules, when conjugated nanofiber scaffolds, will provide the essential chemical signals that promote cell viability, proliferation, polarity in the salivary cell line of interest. These morphological changes will in turn promote the secretory function (salivary production). The nanofiber scaffold consisting of poly(lactic-co-glycolic)acid is conjugated with HA using a polyethylene glycol (PEG) diamine crosslinker. This conjugation was confirmed using fluorescence spectrometry, water contact angle test and immunocytochemistry analysis using confocal microscopy. The effect of HA in promoting cell survival in-vitro was established with MTT assay using SIMS (mouse submandibular immortalized ductal SIMS cells) cells. The effect of HA in improving the apico - basal polarity of SIMS cells will be assessed. Chemical modification of synthetic nanopolymeric scaffolds with ECM molecules e.g., HA, laminin are the next step towards developing "smart scaffolds", that

Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms.

PubMed

Jeong, Shin Young; Kim, Hae Won; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2013-05-01

Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine (RAI) therapy for thyroid cancer. To evaluate the long-term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI ablation. SGS was performed just before RAI ablation (pre-SGS) and ∼5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (U score) was graded, and the ejection fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs. Xerostomia was assessed and compared with the SGS findings. Worsening of the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%, moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score for at least one of four salivary glands. A decrease in EF was observed in 173 of 852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and 43.7% of the patients experienced a decrease in the EF of at least one of the four salivary glands. Bilateral parotid gland dysfunction was the most commonly observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5 years after RAI ablation. Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7 GBq. Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number of dysfunctional salivary glands was correlated with xerostomia (p<0.01). About 20% of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who

Parotitis and Sialendoscopy of the Parotid Gland.

PubMed

Hernandez, Stephen; Busso, Carlos; Walvekar, Rohan R

2016-04-01

Nonneoplastic disorders of the salivary glands involve inflammatory processes. These disorders have been managed conservatively with antibiotics, warm compresses, massage, sialogogues, and adequate hydration. Up to 40% of patients may have an inadequate response or persistent symptoms. When conservative techniques fail, the next step is operative intervention. Sialendoscopy offers a minimally invasive option for the diagnosis and management of chronic inflammatory disorders of the salivary glands and offers the option of gland and function preservation. In this article, we review some of the more common nonneoplastic disorders of the parotid gland, indications for diagnostic and interventional sialendoscopy, and operative techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytokeratin expression in mouse lacrimal gland germ epithelium.

PubMed

Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

2016-05-01

The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relationship between physiological measurements (SFG -scope for growth-) and the functionality of the digestive gland in Mytilus galloprovincialis.

PubMed

Albentosa, Marina; Sánchez-Hernández, Miriam; Campillo, Juan Antonio; Moyano, Francisco Javier

2012-11-01

The present study was aimed to establish the relationship between the functionality of the digestive gland and physiological rates including SFG (scope for growth) in wild mussels, Mytilus galloprovincilis. The experimental set-up consisted in the evaluation of changes in the morphology of the gland, as well as in the activity of some key digestive enzymes (amylase, laminarinase, cellulase and protease) within a broad range of SFG obtained through manipulation of food ration. The higher SFG values were correlated to an increase in both the size of the digestive gland and the activities of enzymes when expressed in relation to individual. In contrast, no clear relations were observed when the activity of enzymes was expressed in relation to soluble protein, with the exception to amylase. The higher protease activities measured in mussels showing lower SFG may reflect an initial stage of catabolic processes intended to compensate the energy deficit produced by food restriction. The potential use of parameters measured in digestive glands in studies of marine pollution was discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Human lacrimal gland regeneration: Perspectives and review of literature

PubMed Central

Tiwari, Shubha; Ali, Mohammad Javed; Vemuganti, Geeta K.

2013-01-01

The human lacrimal gland is an essential component of the lacrimal functional unit (LFU). Any perturbation of this unit can lead to the debilitating morbid condition called the dry eye syndrome (DES). The current line of therapy available for dry eye remains supportive and palliative with the patient being dependent on life long and frequent administration of lubricating eye drops. Even advanced therapies like punctual plugs, cyclosporine B administration, and salivary gland auto-transplantation have led to a limited success. Under these scenarios, the option of cell based therapy needs to be explored to provide better and long term relief to these patients. This review gives an overview of the efforts in lacrimal gland regeneration and examines the past and ongoing research in cell based therapies in animals as well as human lacrimal gland cultures. The authors discuss their first of its kind functionally viable human lacrimal gland in vitro culture system from fresh exenteration specimens. A brief overview of research in near future and the potential implications of lacrimal gland regenerative therapies have been discussed. PMID:24526853

Human lacrimal gland regeneration: Perspectives and review of literature.

PubMed

Tiwari, Shubha; Ali, Mohammad Javed; Vemuganti, Geeta K

2014-01-01

The human lacrimal gland is an essential component of the lacrimal functional unit (LFU). Any perturbation of this unit can lead to the debilitating morbid condition called the dry eye syndrome (DES). The current line of therapy available for dry eye remains supportive and palliative with the patient being dependent on life long and frequent administration of lubricating eye drops. Even advanced therapies like punctual plugs, cyclosporine B administration, and salivary gland auto-transplantation have led to a limited success. Under these scenarios, the option of cell based therapy needs to be explored to provide better and long term relief to these patients. This review gives an overview of the efforts in lacrimal gland regeneration and examines the past and ongoing research in cell based therapies in animals as well as human lacrimal gland cultures. The authors discuss their first of its kind functionally viable human lacrimal gland in vitro culture system from fresh exenteration specimens. A brief overview of research in near future and the potential implications of lacrimal gland regenerative therapies have been discussed.

Eccrine sweat gland development and sweat secretion

PubMed Central

Cui, Chang-Yi; Schlessinger, David

2017-01-01

Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca2+-dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca2+ – and downstream ion channels/transporters in the framework of a Na+-K+-Cl− cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. PMID:26014472

Salivary Glands

MedlinePlus

... salivary gland tumors usually show up as painless enlargements of these glands. Tumors rarely involve more than ... otolaryngologist-head and neck surgeon should check these enlargements. Malignant tumors of the major salivary glands can ...

Hyaluronic Acid Decreases Lipid Synthesis in Sebaceous Glands.

PubMed

Jung, Yu Ra; Hwang, Chul; Ha, Jeong-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Lee, Young-Ho; Kim, Chang-Deok; Lee, Jeung-Hoon; Im, Myung

2017-06-01

Hyaluronic acid (HA) is the major glycosaminoglycan in the extracellular matrix and has been implicated in several functions in skin cells. However, evidence is lacking regarding the HA signaling in sebaceous glands, and its potential role needs to be clarified. We investigated the role of HA in lipid production in sebaceous glands in an experimental study of human sebocytes followed by a clinical study. We first examined the effects of HA on sebaceous glands in hamsters and intradermal injection of HA into hamster auricles decreased both the size of sebaceous glands and the level of lipid production. We demonstrated that human skin sebaceous glands in vivo and sebocytes in vitro express CD44 (HA binding receptor) and that HA downregulates lipid synthesis in a dose-dependent manner. To evaluate the clinical relevance of HA in human skin, 20 oily participants were included in a double-blind, placebo-controlled, split-face study, and the HA-treated side showed a significant decrease in sebum production. The results of this study indicate that HA plays a functional role in human sebaceous gland biology and HA signaling is an effective candidate in the management of disorders in which sebum production is increased. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Salivary gland disease.

PubMed

Thomas, Bethan L; Brown, Jackie E; McGurk, Mark

2010-01-01

Salivary gland disease covers a wide range of pathological entities, including salivary gland-specific disease, as well as manifestations of systemic diseases. This chapter discusses the recent advances in managing obstructive salivary gland disease, the move from gland excision to gland preservation, the dilemmas in diagnosing and managing tumours of the salivary glands, and the international data collection to understand the aetiology and progression of Sjögren's disease. Copyright 2010 S. Karger AG, Basel.

Combined Proteomic and Transcriptomic Interrogation of the Venom Gland of Conus geographus Uncovers Novel Components and Functional Compartmentalization*

PubMed Central

Safavi-Hemami, Helena; Hu, Hao; Gorasia, Dhana G.; Bandyopadhyay, Pradip K.; Veith, Paul D.; Young, Neil D.; Reynolds, Eric C.; Yandell, Mark; Olivera, Baldomero M.; Purcell, Anthony W.

2014-01-01

Cone snails are highly successful marine predators that use complex venoms to capture prey. At any given time, hundreds of toxins (conotoxins) are synthesized in the secretory epithelial cells of the venom gland, a long and convoluted organ that can measure 4 times the length of the snail's body. In recent years a number of studies have begun to unveil the transcriptomic, proteomic and peptidomic complexity of the venom and venom glands of a number of cone snail species. By using a combination of DIGE, bottom-up proteomics and next-generation transcriptome sequencing the present study identifies proteins involved in envenomation and conotoxin maturation, significantly extending the repertoire of known (poly)peptides expressed in the venom gland of these remarkable animals. We interrogate the molecular and proteomic composition of different sections of the venom glands of 3 specimens of the fish hunter Conus geographus and demonstrate regional variations in gene expression and protein abundance. DIGE analysis identified 1204 gel spots of which 157 showed significant regional differences in abundance as determined by biological variation analysis. Proteomic interrogation identified 342 unique proteins including those that exhibited greatest fold change. The majority of these proteins also exhibited significant changes in their mRNA expression levels validating the reliability of the experimental approach. Transcriptome sequencing further revealed a yet unknown genetic diversity of several venom gland components. Interestingly, abundant proteins that potentially form part of the injected venom mixture, such as echotoxins, phospholipase A2 and con-ikots-ikots, classified into distinct expression clusters with expression peaking in different parts of the gland. Our findings significantly enhance the known repertoire of venom gland polypeptides and provide molecular and biochemical evidence for the compartmentalization of this organ into distinct functional entities

Effect of Cisplatin on Parotid Gland Function in Concomitant Radiochemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hey, Jeremias; Setz, Juergen; Gerlach, Reinhard

2009-12-01

Purpose: To determine the influence of concomitant radiochemotherapy with cisplatin on parotid gland tissue complication probability. Methods and Materials: Patients treated with either radiotherapy (n = 61) or concomitant radiochemotherapy with cisplatin (n = 36) for head-and-neck cancer were prospectively evaluated. The dose and volume distributions of the parotid glands were noted in dose-volume histograms. Stimulated salivary flow rates were measured before, during the 2nd and 6th weeks and at 4 weeks and 6 months after the treatment. The data were fit using the normal tissue complication probability model of Lyman. Complication was defined as a reduction of the salivarymore » flow rate to less than 25% of the pretreatment flow rate. Results: The normal tissue complication probability model parameter TD{sub 50} (the dose leading to a complication probability of 50%) was found to be 32.2 Gy at 4 weeks and 32.1 Gy at 6 months for concomitant radiochemotherapy and 41.1 Gy at 4 weeks and 39.6 Gy at 6 months for radiotherapy. The tolerated dose for concomitant radiochemotherapy was at least 7 to 8 Gy lower than for radiotherapy alone at TD{sub 50}. Conclusions: In this study, the concomitant radiochemotherapy tended to cause a higher probability of parotid gland tissue damage. Advanced radiotherapy planning approaches such as intensity-modulated radiotherapy may be partiticularly important for parotid sparing in radiochemotherapy because of cisplatin-related increased radiosensitivity of glands.« less

A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse.

PubMed

Rohde, Kristian; Bering, Tenna; Furukawa, Takahisa; Rath, Martin Fredensborg

2017-10-01

The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis. © 2017 International Society for Neurochemistry.

[The pathology of salivary glands. Tumors of the salivary glands].

PubMed

Mahy, P; Reychler, H

2006-01-01

The management of benign and malignant neoplasms of the salivary glands requires precise knowledge of tumor histogenesis and classification as well as surgical skills. Pleomorphic adenoma and Whartin's tumor are the most frequent tumors in parotid glands while the probability for malignant tumors is higher in other glands, especially in sublingual and minor salivary glands. Those malignant salivary glands tumors are rare and necessitate multidisciplinar staging and management in close collaboration with the pathologist and the radiation oncologist.

The harderian gland: a tercentennial review.

PubMed Central

Payne, A P

1994-01-01

The harderian gland was first described in 1694 by Johann Jacob Harder (1656-1711). It occurs in most terrestrial vertebrates and is located within the orbit where, in some species, it is the largest structure. It may be compound tubular or compound tubuloalveolar, and its secretory duct is usually morphologically distinct only after leaving the substance of the gland to open on the surface of the nictitating membrane. The tubules of the gland are formed of a single layer of columnar epithelial cells surrounded by myoepithelial cells. The chief product(s) of the gland varies between different groups of vertebrates, and epithelial cells possess granules or vacuoles whose contents may be mucous, serous or lipid. In rodents, the gland synthesises lipids, porphyrins and indoles. In the case of lipid vacuoles, the gland is unusual in releasing these by an exocytotic mechanism. It is unclear whether the gland can act both as an exocrine and endocrine organ. There is control of gland structure and synthesis through a variety of humoral agents, including gonadal, thyroid and pituitary hormones; in addition there is a rich autonomic innervation and many neuropeptides have been identified. The proposed functions of the gland are remarkably diverse and include the gland being (1) a source of 'saliva', (2) a site of immune response, (3) a photoprotective organ, (4) part of a retinal-pineal axis, (5) a source of pheromones, (6) a source of thermoregulatory lipids, (7) a site of osmoregulation, and (8) a source of growth factors. The gland is discussed in terms of its embryology and phylogeny, and in relation to ecological variables. Several goals of future research are identified. Images Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 Fig. 25 Fig. 26 Fig. 27 Fig. 28 Fig. 29 Fig. 30 Fig. 31 Fig. 32 Fig. 36 Fig. 37 Fig. 38 Fig. 40 PMID:7559104

Eccrine sweat gland development and sweat secretion.

PubMed

Cui, Chang-Yi; Schlessinger, David

2015-09-01

Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca(2+) -dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers - for example InsP3 and Ca(2+) - and downstream ion channels/transporters in the framework of a Na(+) -K(+) -Cl(-) cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid-base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Ultrastructure of the Intramandibular Gland of Workers and Queens of the Stingless Bee, Melipona quadrifasciata

PubMed Central

Da Cruz-Landim, Carminda; Gracioli-Vitti, Luciana F.; Abdalla, Fábio C.

2011-01-01

The intramandibular glands of workers and queens of Melipona quadrifasciata Lepeletier (Hymenoptera: Apidae), at different ages and from different functional groups, were studied using light and transmission electron microscopy. The results demonstrated that these glands are composed of two types of secretory structures: 1.A hypertrophied epidermis on the dorsal side of the mandible that is an epithelial gland. 2. Free secretory cells filling the inner spaces of the appendices that constitute a unicellular gland. The epithelial gland is larger in the young (1-2-day-old workers), and the gland becomes involuted during the nurse worker stage. The unicellular glands of the workers posses some secretion during all of the studied phases, but secretory activity is more intensive in the foraging workers. Vesicles of secretion are absent in the unicellular glands of queens. These results demonstrate that these glands show functional adaptations in different castes corresponding to the functions of each caste. PMID:22220493

Ultrastructure of the intramandibular gland of workers and queens of the stingless bee, Melipona quadrifasciata.

PubMed

Da Cruz-Landim, Carminda; Gracioli-Vitti, Luciana F; Abdalla, Fábio C

2011-01-01

The intramandibular glands of workers and queens of Melipona quadrifasciata Lepeletier (Hymenoptera: Apidae), at different ages and from different functional groups, were studied using light and transmission electron microscopy. The results demonstrated that these glands are composed of two types of secretory structures: 1.A hypertrophied epidermis on the dorsal side of the mandible that is an epithelial gland. 2. Free secretory cells filling the inner spaces of the appendices that constitute a unicellular gland. The epithelial gland is larger in the young (1-2-day-old workers), and the gland becomes involuted during the nurse worker stage. The unicellular glands of the workers posses some secretion during all of the studied phases, but secretory activity is more intensive in the foraging workers. Vesicles of secretion are absent in the unicellular glands of queens. These results demonstrate that these glands show functional adaptations in different castes corresponding to the functions of each caste.

[The thyroid gland in emotional and pain stress].

PubMed

Akhmetov, I Z

1987-01-01

The reaction of wild rodent thyroid gland on emotional and painful stress appearing as a result of animal's catching has been studied. The thyroid activity has been shown to raise considerably during the primary stage of stress reaction. Later on the function of the gland normalizes in animals without trauma and in traumatized animals it becomes weaker. The complete normalization of the thyroid function in traumatized animals coincides with osteal regeneration according to time.

Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: Comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muenter, Marc W.; Hoffner, Simone; Department of Nuclear Medicine, University of Heidelberg, Heidelberg

2007-03-01

Purpose: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). Methods and Materials: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake ({delta}U) and relative excretion rate ({delta}F) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. Results: In allmore » groups, maximum uptake and relative excretion rate were reduced after RT ({delta}U {<=}0 and {delta}F {<=}0). The reduction was significantly lower for IMRT than for conventional RT. For the parotid glands, the reduction was smaller for the IMRT-low than for the IMRT-high group. For the Amifostine-high and the conventional group the difference was significant only for one parameter ({delta}U, parotid and submandibular glands, p < 0.05). In contrast to this, the difference between the Amifostine-low and the conventional group was always significant or at least showed a clear trend for both changes in U and F. In regard to the endpoint 'reduction of the salivary gland excretion rate of more than 50%,' the dose-response curves yielded D{sub 50}-values of 34.2 {+-} 12.2 Gy for the conventionally treated group and 36.8 {+-} 2.9 Gy for the IMRT group. For the Amifostine group, an increased D{sub 50}-values of 46.3 {+-} 2.3 Gy was obtained. Conclusion: Intensity-modulated RT can significantly reduce the loss of parotid gland function when respecting a certain dose threshold. Conventional RT plus Amifostine prevents reduced salivary gland function only in the patient group treated with <40.6 Gy.« less

Mechanisms and management of dry eye in cataract surgery patients.

PubMed

Sutu, Christine; Fukuoka, Hideki; Afshari, Natalie A

2016-01-01

To provide a summary of the mechanisms that may cause dry eye after cataract surgery and discuss available and upcoming treatment modalities. Development or worsening of dry eye symptoms after cataract surgery is multifactorial with corneal nerve transection, inflammation, goblet cell loss, and meibomian gland dysfunction commonly cited as underlying disorders. With increasing awareness of the prevalence of dry eye disease, current surgical techniques are being analyzed for their contribution to the issue. Although many classic interventions, such as artificial tears and anti-inflammatory drops, remain first-line treatment options, they may not adequately address abnormalities of the tear film. The trend has been to create new drugs and technologies that target meibomian gland deficiencies and restore goblet cell numbers. Therapy for postoperative dry eye symptoms should be determined based on symptom severity and which underlying cause is most prominent at a given time. Patients with high-level risk factors for dry eye should be evaluated preoperatively to determine whether they have preexisting dry eye disease or if they are susceptible to developing disease after surgery.

Design of a Subtarsal Ultrasonic Transducer for Mild Hyperthermia Treatment of Dry Eye Disease.

PubMed

Hynes, Michael B; Bujak, Matthew C; Chérin, Emmanuel; Sade, Shachar; Foster, F Stuart

2016-01-01

Dry eye disease is a disorder of the ocular surface that causes pain and low vision in a significant portion of the adult population. A common cause is obstructive Meibomian gland dysfunction, whereby the Meibomian glands secrete abnormal meibum with a melting point elevated by 3°C-4°C; hence, hyperthermia is the typical treatment. A design is proposed for an ultrasound hyperthermia device made of a transducer contained inside a contact lens with an internal air gap. The transducer heats the posterior of the tarsus, and the air gap provides an air backing to the transducer, preventing direct heating of the cornea. A prototype device was built, and hyperthermia experiments were performed on a porcine subject in vivo. A therapeutic temperature rise of 5°C-7°C was achievable in 10-15 min. The temperature of the cornea did not rise more than 2°C during any of the experiments. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

The frontal gland in workers of Neotropical soldierless termites

NASA Astrophysics Data System (ADS)

Šobotník, Jan; Sillam-Dussès, David; Weyda, František; Dejean, Alain; Roisin, Yves; Hanus, Robert; Bourguignon, Thomas

2010-05-01

The presence of the frontal gland is well established in termite soldiers of Rhinotermitidae, Serritermitidae, and Termitidae. It is one of their main defensive adaptations or even an exclusive weapon. The gland was also occasionally reported in alate imagoes, but never in the worker caste. Here, we report the first observation of a frontal gland in workers of several Neotropical and one African species of Apicotermitinae. The ultrastructure of Aparatermes cingulatus and Anoplotermes nr. subterraneus is described in detail. In these two species, the gland is well-developed, functional and consists of class 1 secretory cells. The presence of envelope cells, wrapping the gland, is an unusual feature, as well as the presence of several zonulae adherens, connecting neighbouring glandular cells. The frontal gland of workers is homologous to this organ in soldiers and imagoes, as evidenced by the same position in the head and its connection to the same muscle. However, the defensive role of the frontal gland in workers remains to be confirmed.

Structure, chemical composition and putative function of the postpharyngeal gland of the emerald cockroach wasp, Ampulex compressa (Hymenoptera, Ampulicidae).

PubMed

Herzner, Gudrun; Ruther, Joachim; Goller, Stephan; Schulz, Stefan; Goettler, Wolfgang; Strohm, Erhard

2011-02-01

The postpharyngeal gland (PPG) plays a major role in the social integration of ant colonies. It had been thought to be restricted to ants but was recently also described for a solitary wasp, the European beewolf (Philanthus triangulum). This finding posed the question whether the gland has evolved independently in the two taxa or has been inherited from a common ancestor and is hence homologous. The latter alternative would be supported if a PPG was found in more basal taxa. Therefore, we examined a species at the base of the Apoidea, the solitary ampulicid wasp Ampulex compressa, for the existence of a PPG. Both sexes of this species possess a cephalic gland that branches off the posterior part of the pharynx, is lined by a cuticular intima and surrounded by a monolayered epithelium with the epithelial cells bearing long hairs. Most of these morphological characteristics conform to those of the PPG of ants and beewolves. Chemical analysis of the gland content revealed that it contains mainly hydrocarbons and that there is a congruence of the pattern of hydrocarbons in the gland, on the cuticle, and in the hemolymph, as has also been reported for both ants and beewolves. Based on these morphological and chemical results we propose that the newly described cephalic gland is a PPG and discuss its possible function in A. compressa. The present study supports the view of a homologous origin of the PPG in the aculeate Hymenoptera. Copyright © 2010 Elsevier GmbH. All rights reserved.

Anatomy and Histology of Rodent and Human Major Salivary Glands

PubMed Central

Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-01-01

Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands. PMID:23209333

Functional adaptations of the transcriptome to mastitis-causing pathogens: the mammary gland and beyond.

PubMed

Loor, Juan J; Moyes, Kasey M; Bionaz, Massimo

2011-12-01

Application of microarrays to the study of intramammary infections in recent years has provided a wealth of fundamental information on the transcriptomics adaptation of tissue/cells to the disease. Due to its heavy toll on productivity and health of the animal, in vivo and in vitro transcriptomics works involving different mastitis-causing pathogens have been conducted on the mammary gland, primarily on livestock species such as cow and sheep, with few studies in non-ruminants. However, the response to an infectious challenge originating in the mammary gland elicits systemic responses in the animal and encompasses tissues such as liver and immune cells in the circulation, with also potential effects on other tissues such as adipose. The susceptibility of the animal to develop mastitis likely is affected by factors beyond the mammary gland, e.g. negative energy balance as it occurs around parturition. Objectives of this review are to discuss the use of systems biology concepts for the holistic study of animal responses to intramammary infection; providing an update of recent work using transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as neutrophils and macrophage responses to mastitis-causing pathogens; discuss the effect of negative energy balance on mastitis predisposition; and analyze the bovine and murine mammary innate-immune responses during lactation and involution using a novel functional analysis approach to uncover potential predisposing factors to mastitis throughout an animal's productive life.

Cellular and molecular specificity of pituitary gland physiology.

PubMed

Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

2012-01-01

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

Submandibular ectopic thyroid with normally located thyroid gland.

PubMed

Yılmaz, Mahmut Sinan; Aytürk, Semra; Güven, Mehmet; Dilek, Fatma Hüsniye

2014-01-01

Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

Histological characterization of peppermint shrimp ( Lysmata wurdemanni) androgenic gland

NASA Astrophysics Data System (ADS)

Liu, Xin; Zhang, Dong; Lin, Tingting

2017-12-01

The androgenic gland (AG) is an important endocrine gland for male reproductive function in crustaceans. In the present study, we investigated the histological characteristics of the androgenic gland of peppermint shrimp, Lysmata wurdemanni. The peppermint shrimp matures as male first, then some individuals may become euhermaphrodite after several moltings (transitional phase). Euhermaphrodite-phase shrimp acts as male at intermolts. However, it can be fertilized as a female immediately after molting. Considering the male reproductive function acts in its lifespan except for at larval stages, and female reproductive system starts to develop at transitional phase, we hypothesized that AG activity might be reduced to allow and promote vitellogenesis onset in early transitional phase and the following euhermaphrodite phase. So AG cell structure might be different in three phases in L. wurdemanni. The results showed that AG exists in the male in transitional and euhermaphrodite phases. The gland cell clusters surrounding the ejaculatory ducts locate at the roots of the fifth pereopods. The nucleus diameters are similar in the three phases while the nucleus- to-cell ratio is the lowest in euhermaphrodite phase. Our results indicated that for the individuals that will become euhermaphrodite, the cellular structure of AG changes since transitional phase. Male reproductive function which is still available in euhermaphrodite-phase shrimp should be due to the existence of the gland.

Evolution of immune functions of the mammary gland and protection of the infant.

PubMed

Goldman, Armond S

2012-06-01

Abstract The evolution of immunological agents in milk is intertwined with the general aspects of the evolution of the mammary gland. In that respect, mammalian precursors emerged from basal amniotes some 300 million years ago. In contrast to the predominant dinosaurs, proto-mammals possessed a glandular skin. A secondary palate in the roof of the mouth that directed airflow from the nostrils to the oropharynx and thus allowed mammals to ingest and breathe simultaneously first appeared in cynodonts 230 million years ago. This set the stage for mammalian newborns to nurse from the future mammary gland. Interplays between environmental and genetic changes shaped mammalian evolution including the mammary gland from dermal glands some 160 millions of years ago. It is likely that secretions from early mammary glands provided nutrients and immunological agents for the infant. Natural selection culminated in milks uniquely suited to nourish and protect infants of each species. In human milk, antimicrobial, anti-inflammatory, and immunoregulatory agents and living leukocytes are qualitatively or quantitatively different from those in other mammalian milks. Those in human milk compensate for developmental delays in the immunological system of the recipient infant. Consequently, the immune system in human milk provided by evolution is much of the basis for encouraging breastfeeding for human infants.

Proteomic analysis in the Dufour's gland of Africanized Apis mellifera workers (Hymenoptera: Apidae).

PubMed

Teixeira, Aparecida das Dores; Games, Patricia D; Katz, Benjamin B; Tomich, John M; Zanuncio, José C; Serrão, José Eduardo

2017-01-01

The colony of eusocial bee Apis mellifera has a reproductive queen and sterile workers performing tasks such as brood care and foraging. Chemical communication plays a crucial role in the maintenance of sociability in bees with many compounds released by the exocrine glands. The Dufour's gland is a non-paired gland associated with the sting apparatus with important functions in the communication between members of the colony, releasing volatile chemicals that influence workers roles and tasks. However, the protein content in this gland is not well studied. This study identified differentially expressed proteins in the Dufour's glands of nurse and forager workers of A. mellifera through 2D-gel electrophoresis and mass spectrometry. A total of 131 spots showed different expression between nurse and forager bees, and 28 proteins were identified. The identified proteins were categorized into different functions groups including protein, carbohydrate, energy and lipid metabolisms, cytoskeleton-associated proteins, detoxification, homeostasis, cell communication, constitutive and allergen. This study provides new insights of the protein content in the Dufour's gland contributing to a more complete understanding of the biological functions of this gland in honeybees.

Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway

PubMed Central

Liu, Xibao; Gong, Baijuan; de Souza, Lorena Brito; Ong, Hwei Ling; Subedi, Krishna P.; Cheng, Kwong Tai; Swaim, William; Zheng, Changyu; Mori, Yasuo; Ambudkar, Indu S.

2017-01-01

Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3–mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2+/+, but not those from TRPM2−/− mice, displayed an increase in the concentrations of mitochondrial Ca2+ and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE. In a salivary gland cell line, silencing the mitochondrial Ca2+ uniporter or caspase-3 or treatment with inhibitors of TRPM2 or caspase-3 prevented irradiation-induced loss of STIM1 and SOCE. Expression of exogenous STIM1 in the salivary glands of irradiated mice increased SOCE and fluid secretion. We suggest that targeting the mechanisms underlying the loss of STIM1 would be a potentially useful approach for preserving salivary gland function after radiation therapy. PMID:28588080

Comparative study of the labial gland secretion in termites (Isoptera).

PubMed

Sillam-Dussès, David; Krasulová, Jana; Vrkoslav, Vladimír; Pytelková, Jana; Cvačka, Josef; Kutalová, Kateřina; Bourguignon, Thomas; Miura, Toru; Šobotník, Jan

2012-01-01

Labial glands are present in all castes and developmental stages of all termite species. In workers, their secretion contains a food-marking pheromone and digestive enzymes, while soldier secretion plays a defensive role. However, these functions were studied only in a limited set of species, and do not allow drawing general conclusions. Hence, we have investigated the chemical composition of the labial gland extracts from soldiers and workers in 15 termite species belonging to 6 families using an integrative approach based on proteomic and small-molecule profiling. We confirmed the presence of hydroquinone and cellulase in the labial glands of workers, and we identified new toxic compounds in soldiers and workers of several species. Our results highlight the dual role of labial gland secretion, i.e. the defensive role in soldiers and workers of several termite species, and the digestive function in workers.

GABAergic signaling in the rat pineal gland

PubMed Central

Yu, Haijie; Benitez, Sergio G.; Jung, Seung-Ryoung; Farias Altamirano, Luz E.; Kruse, Martin; Seo, Jong-Bae; Koh, Duk-Su; Muñoz, Estela M.; Hille, Bertil

2017-01-01

Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic enzyme GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca2+ channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48–72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found. PMID:27019076

Matrigel basement membrane matrix induces eccrine sweat gland cells to reconstitute sweat gland-like structures in nude mice.

PubMed

Li, Haihong; Chen, Lu; Zeng, Shaopeng; Li, Xuexue; Zhang, Xiang; Lin, Changmin; Zhang, Mingjun; Xie, Sitian; He, Yunpu; Shu, Shenyou; Yang, Lvjun; Tang, Shijie; Fu, Xiaobing

2015-03-01

Severe burn results in irreversible damage to eccrine sweat glands, for which no effective treatment is available. Interaction between the extracellular matrix and epithelial cells is critical for proper three-dimensional organization and function of the epithelium. Matrigel-embedded eccrine sweat gland cells were subcutaneously implanted into the inguinal regions of nude mice. Two weeks later, the Matrigel plugs were removed and evaluated for series of detection items. Sweat gland cells developed into sweat gland-like structures in the Matrigel plugs based on: (1) de novo formation of tubular-like structures with one or more hollow lumens, (2) expression of epithelial and sweat gland markers (pancytokeratin, CK5/7/14/19, α-SMA and CEA), (3) basement membrane formation, (4) myoepithelial cells presenting in and encompassing the tubular-like structures, (5) cellular polarization, evident by the expression of tight junction proteins (claudin-1 and ZO-2), anchoring junctions (desmoglein-1 and -2 and E-cadherin) and CEA in the luminal membrane, (6) expression of proteins related to sweat secretion and absorption (Na(+)-K(+)-ATPase α/β, Na(+)-K(+)-2Cl-cotranspoter 1, Na(+)/H(+) exchanger 1, aquaporin-5, epithelial sodium channel, cystic fibrosis transmembrane conductance regulator, potassium channel and vacuolar-type H+-ATPase), and (7) about 20% of the tubular-like structures are de novo coils and 80% are de novo ducts. This study provides not only an excellent model to study eccrine sweat gland development, cytodifferentiation and reconstitution, but also an in vivo model for regeneration of eccrine sweat glands. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative Study of the Labial Gland Secretion in Termites (Isoptera)

PubMed Central

Sillam-Dussès, David; Krasulová, Jana; Vrkoslav, Vladimír; Pytelková, Jana; Cvačka, Josef; Kutalová, Kateřina; Bourguignon, Thomas; Miura, Toru; Šobotník, Jan

2012-01-01

Labial glands are present in all castes and developmental stages of all termite species. In workers, their secretion contains a food-marking pheromone and digestive enzymes, while soldier secretion plays a defensive role. However, these functions were studied only in a limited set of species, and do not allow drawing general conclusions. Hence, we have investigated the chemical composition of the labial gland extracts from soldiers and workers in 15 termite species belonging to 6 families using an integrative approach based on proteomic and small-molecule profiling. We confirmed the presence of hydroquinone and cellulase in the labial glands of workers, and we identified new toxic compounds in soldiers and workers of several species. Our results highlight the dual role of labial gland secretion, i.e. the defensive role in soldiers and workers of several termite species, and the digestive function in workers. PMID:23071569

Proteomic analysis in the Dufour’s gland of Africanized Apis mellifera workers (Hymenoptera: Apidae)

PubMed Central

2017-01-01

The colony of eusocial bee Apis mellifera has a reproductive queen and sterile workers performing tasks such as brood care and foraging. Chemical communication plays a crucial role in the maintenance of sociability in bees with many compounds released by the exocrine glands. The Dufour’s gland is a non-paired gland associated with the sting apparatus with important functions in the communication between members of the colony, releasing volatile chemicals that influence workers roles and tasks. However, the protein content in this gland is not well studied. This study identified differentially expressed proteins in the Dufour’s glands of nurse and forager workers of A. mellifera through 2D-gel electrophoresis and mass spectrometry. A total of 131 spots showed different expression between nurse and forager bees, and 28 proteins were identified. The identified proteins were categorized into different functions groups including protein, carbohydrate, energy and lipid metabolisms, cytoskeleton-associated proteins, detoxification, homeostasis, cell communication, constitutive and allergen. This study provides new insights of the protein content in the Dufour’s gland contributing to a more complete understanding of the biological functions of this gland in honeybees. PMID:28542566

Rectal Glands of Marine and Fresh-Water Sharks: Comparative Histology.

PubMed

Oguri, M

1964-05-29

The rectal glands of elasmobranchs perform the function of salt-excreting organs. These glands are smaller and show regressive changes in specimens of the bull shark, Carcharhinus leucas found in fresh-water environment, compared with specimens of this and other species from a marine habitat.

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori.

PubMed

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-04-22

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography-tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study.

Reproductive biology in Anophelinae mosquitoes (Diptera, Culicidae): Fine structure of the female accessory gland.

PubMed

Laghezza Masci, Valentina; Di Luca, Marco; Gambellini, Gabriella; Taddei, Anna Rita; Belardinelli, Maria Cristina; Guerra, Laura; Mazzini, Massimo; Fausto, Anna Maria

2015-07-01

The morphology and ultrastructure of female accessory reproductive glands of Anopheles maculipennis s.s., Anopheles labranchiae and Anopheles stephensi were investigated by light and electron microscopy. The reproductive system in these species is characterized by two ovaries, two lateral oviducts, a single spermatheca and a single accessory gland. The gland is globular and has a thin duct which empties into the vagina, near the opening of the spermathecal duct. Significant growth of the accessory reproductive gland is observed immediately after blood meal, but not at subsequent digestion steps. At ultrastructural level, the gland consists of functional glandular units belonging to type 3 ectodermal glands. The secretory cells are elongated and goblet shaped, with most of their cytoplasm and large nucleus in the basal part, close to the basement lamella. Finely fibrous electron-transparent material occupies the secretory cavity that is in contact with the end of a short efferent duct (ductule) emerging from the gland duct. The present study is the first detailed description of female accessory gland ultrastructure in Anophelinae and provides insights into the gland's functional role in the reproductive biology of these insects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential for daily supplementation of n-3 fatty acids to reverse symptoms of dry eye in mice.

PubMed

Harauma, Akiko; Saito, Junpei; Watanabe, Yoshitake; Moriguchi, Toru

2014-06-01

The purpose of this study was to determine the change in tear volume, as a predominant symptom of dry eye syndrome, in dietary n-3 fatty acid deficient mice compared with n-3 fatty acid adequate mice. The tear volume in n-3 fatty acid deficient mice was significantly lower than that in n-3 fatty acid adequate mice. In addition, the concentration of n-3 fatty acid in the lacrimal and meibomian glands, which affects the production of tears, was markedly decreased compared with n-3 fatty acid adequate mice. However, the tear volume recovered almost completely after one week of continuous administration of fish oil containing EPA and DHA in n-3 fatty acid deficient mice. Also, the concentration of DHA in the meibomian gland of n-3 fatty acid deficient group recovered to approximately 80% more than that of n-3 fatty acid adequate group. These results suggested that dietary n-3 fatty acids deficiency showed reversible dry eye syndrome, and that n-3 fatty acids have an important role in the production of tears. Copyright © 2014 Elsevier Ltd. All rights reserved.

GABAergic signaling in the rat pineal gland.

PubMed

Yu, Haijie; Benitez, Sergio G; Jung, Seung-Ryoung; Farias Altamirano, Luz E; Kruse, Martin; Seo, Jong Bae; Koh, Duk-Su; Muñoz, Estela M; Hille, Bertil

2016-08-01

Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here, we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB 1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca(2+) channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48-72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus, strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autocrine-paracrine regulation of the mammary gland.

PubMed

Weaver, S R; Hernandez, L L

2016-01-01

The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

PubMed

Taniguchi, Kiichiro; Kokuryo, Akihiko; Imano, Takao; Minami, Ryunosuke; Nakagoshi, Hideki; Adachi-Yamada, Takashi

2014-12-20

In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate

Post-metamorphic development of skin glands in a true toad: Parotoids versus dorsal skin.

PubMed

Regueira, Eleonora; Dávila, Camila; Sassone, Alina G; O'Donohoe, María E Ailín; Hermida, Gladys N

2017-05-01

Chemical defenses in amphibians are a common antipredatory and antimicrobial strategy related to the presence of dermal glands that synthesize and store toxic or unpalatable substances. Glands are either distributed throughout the skin or aggregated in multiglandular structures, being the parotoids the most ubiquitous macrogland in toads of Bufonidae. Even though dermal glands begin to develop during late-larval stages, many species, including Rhinella arenarum, have immature glands by the end of metamorphosis, and their post-metamorphic growth is unknown. Herein, we compared the post-metamorphic development of parotoids and dorsal glands by histological and allometric studies in a size series of R. arenarum. Histological and histochemical studies to detect proteins, acidic glycoconjugates, and catecholamines, showed that both, parotoids and dorsal glands, acquire characteristics of adults in individuals larger than 50 mm; that is, a moment in which the cryptic coloration disappears. Parotoid height increased allometrically as a function of body size, whereas the size of small dorsal glands decreased with body size. The number of glands in the dorsum was not linearly related to body size, appearing to be an individual characteristic. Only adult specimens had intraepithelial granular glands in the duct of the largest glands of the parotoids. Since toxic secretions accumulate in the central glands of parotoids, allometric growth of parotoids may translate into greater protection from predators in the largest animals. Conversely, large glands in the dorsum, which produce a proteinaceous secretion of unknown function, grow isometrically to body size. Some characteristics, like intraepithelial glands in the ducts and basophilic glands in the dorsum, are limited to adults. © 2017 Wiley Periodicals, Inc.

Hypertensive crisis caused by electrocauterization of the adrenal gland during hepatectomy.

PubMed

Doo, A Ram; Son, Ji-Seon; Han, Young-Jin; Yu, Hee Chul; Ko, Seonghoon

2015-02-14

Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is very rare during operation except pheochromocytoma, but it can be a fatal and embarrassing to surgeons and anesthesiologists. The right adrenal gland can be electrocauterized during a right hemi-hepatectomy. We report a case of hypertensive crisis during right hemi-hepatectomy in which the right adrenal gland was stimulated by monopolar electrocautery in a patient with normal neuroendocrine function. A 73-year-old man with hepatocellular carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the surgery, the patient's blood pressure increased abruptly from 100/40 to over 350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The surgeon had cauterized the right adrenal gland using monopolar electrocautery to separate the liver from the adrenal gland immediately prior to the event. Approximately 3 minutes after suspending the operation, blood pressure returned to baseline levels. After the event, the operation was successfully completed without any complication. Hormonal studies and iodine-123 meta-iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a pheochromocytoma. Operations such as hepatectomy that stimulate the adrenal gland may lead to an unexpected catecholamine surge and result in hypertensive crisis, even if neuroendocrine function of the adrenal gland is normal.

Diagnosis and management of endocrine gland neoplasmas. Revision 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weller, R.E.

1994-03-01

Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. This discussion will focus on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal, and parathyroid glands, and pancreas in companion animals and will concentrate on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis.

[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].

PubMed

Korkushko, O V; Lapin, B A; Goncharova, N D; Khavinson, V Kh; Shatilo, V B; Vengerin, A A; Antoniuk-Shcheglova, I A; Magdich, L V

2007-01-01

In the course of aging both monkeys and people reveal decreased night and average daily level of melatonin in the blood plasma and reduced hormone circadian rhythm amplitude, which evidence the disorder of the pineal gland melatonin releasing function. Peptide preparations of the pineal gland (Epithalamin--a complex of peptides isolated from the pineal gland and Epitalon--synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori

PubMed Central

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-01-01

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography–tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study. PMID:27102218

[The history of discovery of bulbourethral glands].

PubMed

Kutia, S A; Sataeva, T P; Nikolaeva, N G; Printseva, N Yu; Moroz, G A

2016-08-01

The article outlines the chronology of the discovery of the bulbourethral glands. Their first image appeared in 1600 in a collection of anatomical tables by Italian anatomist Hieronymus Fabricius of Acquapendente. In the scientific literature, they were first mentioned in one of the editions of "Journal des scavans" in 1684 as discovered by the French surgeon Jean Mry. The first detailed description of the structure, topography and function of these glands was presented in the work of English physician and anatomist William Cowper in 1699.

Adrenal Gland Tumors: Statistics

MedlinePlus

... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

Ophthalmological outcome after resection of tumors based on the pineal gland.

PubMed

Hart, Michael G; Sarkies, Nicholas J; Santarius, Thomas; Kirollos, Ramez W

2013-08-01

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland. Review of a retrospective case series was performed and included consecutive patients who underwent surgery performed by a consultant neurosurgeon between 2002 and 2011. Only tumors specifically based on the pineal gland were included; tumors encroaching on the pineal gland from other regions were excluded. All patients with visual signs and/or symptoms were reviewed by a specialist consultant neuroophthalmologist to accurately characterize the nature of their deficits. Visual disturbance was defined as visual symptoms caused by a disturbance of ocular motility. A total of 20 patients underwent resection of pineal gland tumors. Complete resection was obtained in 85%, and there were no perioperative deaths. Visual disturbance was present in 35% at presentation; of those who had normal ocular motility preoperatively 82% had normal motility postoperatively. In total, 55% of patients had residual visual disturbance postoperatively. Although upward gaze tended to improve, significant functional deficits remained, particularly with regard to complex convergence and accommodation dysfunction. Prisms were used in 25% but were only ever partially effective. Visual outcome was only related to preoperative visual status and tumor volume (multivariate analysis). Long-term visual morbidity after pineal gland tumor resection is common and leads to significant functional impairment. Improvement in deficits rarely occurs spontaneously, and prisms only have limited effectiveness, probably due to the dynamic nature of supranuclear ocular movement coordination.

Minor Salivary Gland Transplantation for Severe Dry Eyes.

PubMed

Wakamatsu, Tais Hitomi; SantʼAnna, Ana Estela Besteti Pires Ponce; Cristovam, Priscila Cardoso; Alves, Venâncio Avancini Ferreira; Wakamatsu, Alda; Gomes, José Alvaro Pereira

2017-11-01

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.

Microdissection of Black Widow Spider Silk-producing Glands

PubMed Central

Hsia, Yang; Gnesa, Eric; Zhao, Liang; Franz, Andreas; Vierra, Craig

2011-01-01

Modern spiders spin high-performance silk fibers with a broad range of biological functions, including locomotion, prey capture and protection of developing offspring 1,2. Spiders accomplish these tasks by spinning several distinct fiber types that have diverse mechanical properties. Such specialization of fiber types has occurred through the evolution of different silk-producing glands, which function as small biofactories. These biofactories manufacture and store large quantities of silk proteins for fiber production. Through a complex series of biochemical events, these silk proteins are converted from a liquid into a solid material upon extrusion. Mechanical studies have demonstrated that spider silks are stronger than high-tensile steel 3. Analyses to understand the relationship between the structure and function of spider silk threads have revealed that spider silk consists largely of proteins, or fibroins, that have block repeats within their protein sequences 4. Common molecular signatures that contribute to the incredible tensile strength and extensibility of spider silks are being unraveled through the analyses of translated silk cDNAs. Given the extraordinary material properties of spider silks, research labs across the globe are racing to understand and mimic the spinning process to produce synthetic silk fibers for commercial, military and industrial applications. One of the main challenges to spinning artificial spider silk in the research lab involves a complete understanding of the biochemical processes that occur during extrusion of the fibers from the silk-producing glands. Here we present a method for the isolation of the seven different silk-producing glands from the cobweaving black widow spider, which includes the major and minor ampullate glands [manufactures dragline and scaffolding silk] 5,6, tubuliform [synthesizes egg case silk] 7,8, flagelliform [unknown function in cob-weavers], aggregate [makes glue silk], aciniform [synthesizes prey

Microdissection of black widow spider silk-producing glands.

PubMed

Jeffery, Felicia; La Mattina, Coby; Tuton-Blasingame, Tiffany; Hsia, Yang; Gnesa, Eric; Zhao, Liang; Franz, Andreas; Vierra, Craig

2011-01-11

Modern spiders spin high-performance silk fibers with a broad range of biological functions, including locomotion, prey capture and protection of developing offspring. Spiders accomplish these tasks by spinning several distinct fiber types that have diverse mechanical properties. Such specialization of fiber types has occurred through the evolution of different silk-producing glands, which function as small biofactories. These biofactories manufacture and store large quantities of silk proteins for fiber production. Through a complex series of biochemical events, these silk proteins are converted from a liquid into a solid material upon extrusion. Mechanical studies have demonstrated that spider silks are stronger than high-tensile steel. Analyses to understand the relationship between the structure and function of spider silk threads have revealed that spider silk consists largely of proteins, or fibroins, that have block repeats within their protein sequences. Common molecular signatures that contribute to the incredible tensile strength and extensibility of spider silks are being unraveled through the analyses of translated silk cDNAs. Given the extraordinary material properties of spider silks, research labs across the globe are racing to understand and mimic the spinning process to produce synthetic silk fibers for commercial, military and industrial applications. One of the main challenges to spinning artificial spider silk in the research lab involves a complete understanding of the biochemical processes that occur during extrusion of the fibers from the silk-producing glands. Here we present a method for the isolation of the seven different silk-producing glands from the cobweaving black widow spider, which includes the major and minor ampullate glands [manufactures dragline and scaffolding silk], tubuliform [synthesizes egg case silk], flagelliform [unknown function in cob-weavers], aggregate [makes glue silk], aciniform [synthesizes prey wrapping and egg

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

PubMed

Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

2014-07-31

MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

[Effect of pineal gland peptides on morphofunctional structure of the pancreas in ageing].

PubMed

Ryzhak, A P; Kostiuchek, I N; Kvetnoĭ, I M

2007-01-01

A study of pineal gland peptides effect on morphology and functions of the pancreas in the model of premature ageing in rats was performed with respect to the need in methods for premature ageing prevention. Structural, morphological and functional alterations in pancreas tissue, suggesting premature ageing of the gland, were identified by methods of immunohistochemistry and electronic microscopy. There was registered a geroprotective effect of the pineal gland peptides on pancreas tissue, manifested in the resistance of the latter to the impact of stress factors entailing premature ageing.

Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avila, Jennifer L.; Grundmann, Oliver; Burd, Randy

2009-02-01

Purpose: Radiotherapy for head-and-neck cancer causes adverse secondary side effects in the salivary glands and results in diminished quality of life for the patient. A previous in vivo study in parotid salivary glands demonstrated that targeted head-and-neck irradiation resulted in marked increases in phosphorylated p53 (serine{sup 18}) and apoptosis, which was suppressed in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Methods and Materials: Transgenic and knockout mouse models were exposed to irradiation, and p53-mediated transcription, apoptosis, and salivary gland dysfunction were analyzed. Results: The proapoptotic p53 target genes PUMA and Bax were induced in parotid salivary glandsmore » of mice at early time points after therapeutic radiation. This dose-dependent induction requires expression of p53 because no radiation-induced expression of PUMA and Bax was observed in p53-/- mice. Radiation also induced apoptosis in the parotid gland in a dose-dependent manner, which was p53 dependent. Furthermore, expression of p53 was required for the acute and chronic loss of salivary function after irradiation. In contrast, apoptosis was not induced in p53-/- mice, and their salivary function was preserved after radiation exposure. Conclusions: Apoptosis in the salivary glands after therapeutic head-and-neck irradiation is mediated by p53 and corresponds to salivary gland dysfunction in vivo.« less

Pituitary gland volumes in bipolar disorder.

PubMed

Clark, Ian A; Mackay, Clare E; Goodwin, Guy M

2014-12-01

Bipolar disorder has been associated with increased Hypothalamic-Pituitary-Adrenal axis function. The mechanism is not well understood, but there may be associated increases in pituitary gland volume (PGV) and these small increases may be functionally significant. However, research investigating PGV in bipolar disorder reports mixed results. The aim of the current study was twofold. First, to assess PGV in two novel samples of patients with bipolar disorder and matched healthy controls. Second, to perform a meta-analysis comparing PGV across a larger sample of patients and matched controls. Sample 1 consisted of 23 established patients and 32 matched controls. Sample 2 consisted of 39 medication-naïve patients and 42 matched controls. PGV was measured on structural MRI scans. Seven further studies were identified comparing PGV between patients and matched controls (total n; 244 patients, 308 controls). Both novel samples showed a small (approximately 20mm(3) or 4%), but non-significant, increase in PGV in patients. Combining the two novel samples showed a significant association of age and PGV. Meta-analysis showed a trend towards a larger pituitary gland in patients (effect size: .23, CI: -.14, .59). While results suggest a possible small difference in pituitary gland volume between patients and matched controls, larger mega-analyses with sample sizes greater even than those used in the current meta-analysis are still required. There is a small but potentially functionally significant increase in PGV in patients with bipolar disorder compared to controls. Results demonstrate the difficulty of finding potentially important but small effects in functional brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

"Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

PubMed

Tóth, Balázs I; Oláh, Attila; Szöllosi, Attila G; Czifra, Gabriella; Bíró, Tamás

2011-06-01

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

Impaired mitochondria and intracellular calcium transients in the salivary glands of obese rats.

PubMed

Ittichaicharoen, Jitjiroj; Apaijai, Nattayaporn; Tanajak, Pongpan; Sa-Nguanmoo, Piangkwan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-04-01

Long-term consumption of a high-fat diet (HFD) causes not only obese-insulin resistance, but is also associated with mitochondrial dysfunction in several organs. However, the effect of obese-insulin resistance on salivary glands has not been investigated. We hypothesized that obese-insulin resistance induced by HFD impaired salivary gland function by reducing salivation, increasing inflammation, and fibrosis, as well as impairing mitochondrial function and calcium transient signaling. Male Wistar rats (200-220 g) were fed either a ND or an HFD (n = 8/group) for 16 weeks. At the end of week 16, salivary flow rates, metabolic parameters, and plasma oxidative stress were determined. Rats were then sacrificed and submandibular glands were removed to determine inflammation, fibrosis, apoptosis, mitochondrial function and dynamics, and intracellular calcium transient signaling. Long-term consumption of an HFD caused obese-insulin resistance and increased oxidative stress, fibrosis, inflammation, and apoptosis in the salivary glands. In addition, impaired mitochondrial function, as indicated by increased mitochondrial reactive oxygen species, mitochondrial membrane depolarization, and mitochondrial swelling in salivary glands and impaired intracellular calcium regulation, as indicated by a reduced intracellular calcium transient rising rate, decay rates, and amplitude of salivary acinar cells, were observed in HFD-fed rats. However, salivary flow rate and level of aquaporin 5 protein were not different between both groups. Although HFD consumption did not affect salivation, it caused obese-insulin resistance, leading to pathophysiological alteration of salivary glands, including impaired intracellular calcium transients, increased oxidative stress and inflammation, and salivary mitochondrial dysfunction.

Benign Pediatric Salivary Gland Lesions.

PubMed

Carlson, Eric R; Ord, Robert A

2016-02-01

Salivary gland lesions are rare in pediatric patients. In addition, the types of salivary gland tumors are different in their distribution in specific sites in the major and minor salivary glands in children compared with adults. This article reviews benign neoplastic and nonneoplastic salivary gland disorders in pediatric patients to help clinicians to develop an orderly differential diagnosis that will lead to expedient treatment of pediatric patients with salivary gland lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion.

PubMed

Sasaki, S; Watanabe, J; Ohtaki, H; Matsumoto, M; Murai, N; Nakamachi, T; Hannibal, J; Fahrenkrug, J; Hashimoto, H; Watanabe, H; Sueki, H; Honda, K; Miyazaki, A; Shioda, S

2017-02-01

Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is required. Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits pleiotropic functions that are mediated via its receptors [PACAP-specific receptor (PAC1R), vasoactive intestinal peptide (VIP) receptor type 1 (VPAC1R) and VPAC2R]. Although some studies have suggested a role for PACAP in the skin and several exocrine glands, the effects of PACAP on the process of eccrine sweat secretion have not been examined. To investigate the effect of PACAP on eccrine sweat secretion. Reverse transcriptase-polymerase chain reaction and immunostaining were used to determine the expression and localization of PACAP and its receptors in mouse and human eccrine sweat glands. We injected PACAP subcutaneously into the footpads of mice and used the starch-iodine test to visualize sweat-secreting glands. Immunostaining showed PACAP and PAC1R expression by secretory cells from mouse and human sweat glands. PACAP immunoreactivity was also localized in nerve fibres around eccrine sweat glands. PACAP significantly promoted sweat secretion at the injection site, and this could be blocked by the PAC1R-antagonist PACAP6-38. VIP, an agonist of VPAC1R and VPAC2R, failed to induce sweat secretion. This is the first report demonstrating that PACAP may play a crucial role in sweat secretion via its action on PAC1R located in eccrine sweat glands. The mechanisms underlying the role of PACAP in sweat secretion may provide new therapeutic options to combat sweating disorders. © 2016 British Association of Dermatologists.

Transcriptomic Analysis of the Salivary Glands of an Invasive Whitefly

PubMed Central

Su, Yun-Lin; Li, Jun-Min; Li, Meng; Luan, Jun-Bo; Ye, Xiao-Dong; Wang, Xiao-Wei; Liu, Shu-Sheng

2012-01-01

Background Some species of the whitefly Bemisia tabaci complex cause tremendous losses to crops worldwide through feeding directly and virus transmission indirectly. The primary salivary glands of whiteflies are critical for their feeding and virus transmission. However, partly due to their tiny size, research on whitefly salivary glands is limited and our knowledge on these glands is scarce. Methodology/Principal Findings We sequenced the transcriptome of the primary salivary glands of the Mediterranean species of B. tabaci complex using an effective cDNA amplification method in combination with short read sequencing (Illumina). In a single run, we obtained 13,615 unigenes. The quantity of the unigenes obtained from the salivary glands of the whitefly is at least four folds of the salivary gland genes from other plant-sucking insects. To reveal the functions of the primary glands, sequence similarity search and comparisons with the whole transcriptome of the whitefly were performed. The results demonstrated that the genes related to metabolism and transport were significantly enriched in the primary salivary glands. Furthermore, we found that a number of highly expressed genes in the salivary glands might be involved in secretory protein processing, secretion and virus transmission. To identify potential proteins of whitefly saliva, the translated unigenes were put into secretory protein prediction. Finally, 295 genes were predicted to encode secretory proteins and some of them might play important roles in whitefly feeding. Conclusions/Significance: The combined method of cDNA amplification, Illumina sequencing and de novo assembly is suitable for transcriptomic analysis of tiny organs in insects. Through analysis of the transcriptome, genomic features of the primary salivary glands were dissected and biologically important proteins, especially secreted proteins, were predicted. Our findings provide substantial sequence information for the primary salivary glands

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles.

PubMed

Andreasen, Simon; Tan, Qihua; Agander, Tina Klitmøller; Steiner, Petr; Bjørndal, Kristine; Høgdall, Estrid; Larsen, Stine Rosenkilde; Erentaite, Daiva; Olsen, Caroline Holkmann; Ulhøi, Benedicte Parm; von Holstein, Sarah Linéa; Wessel, Irene; Heegaard, Steffen; Homøe, Preben

2018-02-21

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid

Analysis of the Salivary Gland Transcriptome of Frankliniella occidentalis

PubMed Central

Stafford-Banks, Candice A.; Rotenberg, Dorith; Johnson, Brian R.; Whitfield, Anna E.; Ullman, Diane E.

2014-01-01

Saliva is known to play a crucial role in insect feeding behavior and virus transmission. Currently, little is known about the salivary glands and saliva of thrips, despite the fact that Frankliniella occidentalis (Pergande) (the western flower thrips) is a serious pest due to its destructive feeding, wide host range, and transmission of tospoviruses. As a first step towards characterizing thrips salivary gland functions, we sequenced the transcriptome of the primary salivary glands of F. occidentalis using short read sequencing (Illumina) technology. A de novo-assembled transcriptome revealed 31,392 high quality contigs with an average size of 605 bp. A total of 12,166 contigs had significant BLASTx or tBLASTx hits (E≤1.0E−6) to known proteins, whereas a high percentage (61.24%) of contigs had no apparent protein or nucleotide hits. Comparison of the F. occidentalis salivary gland transcriptome (sialotranscriptome) against a published F. occidentalis full body transcriptome assembled from Roche-454 reads revealed several contigs with putative annotations associated with salivary gland functions. KEGG pathway analysis of the sialotranscriptome revealed that the majority (18 out of the top 20 predicted KEGG pathways) of the salivary gland contig sequences match proteins involved in metabolism. We identified several genes likely to be involved in detoxification and inhibition of plant defense responses including aldehyde dehydrogenase, metalloprotease, glucose oxidase, glucose dehydrogenase, and regucalcin. We also identified several genes that may play a role in the extra-oral digestion of plant structural tissues including β-glucosidase and pectin lyase; and the extra-oral digestion of sugars, including α-amylase, maltase, sucrase, and α-glucosidase. This is the first analysis of a sialotranscriptome for any Thysanopteran species and it provides a foundational tool to further our understanding of how thrips interact with their plant hosts and the viruses

Analysis of the salivary gland transcriptome of Frankliniella occidentalis.

PubMed

Stafford-Banks, Candice A; Rotenberg, Dorith; Johnson, Brian R; Whitfield, Anna E; Ullman, Diane E

2014-01-01

Saliva is known to play a crucial role in insect feeding behavior and virus transmission. Currently, little is known about the salivary glands and saliva of thrips, despite the fact that Frankliniella occidentalis (Pergande) (the western flower thrips) is a serious pest due to its destructive feeding, wide host range, and transmission of tospoviruses. As a first step towards characterizing thrips salivary gland functions, we sequenced the transcriptome of the primary salivary glands of F. occidentalis using short read sequencing (Illumina) technology. A de novo-assembled transcriptome revealed 31,392 high quality contigs with an average size of 605 bp. A total of 12,166 contigs had significant BLASTx or tBLASTx hits (E≤1.0E-6) to known proteins, whereas a high percentage (61.24%) of contigs had no apparent protein or nucleotide hits. Comparison of the F. occidentalis salivary gland transcriptome (sialotranscriptome) against a published F. occidentalis full body transcriptome assembled from Roche-454 reads revealed several contigs with putative annotations associated with salivary gland functions. KEGG pathway analysis of the sialotranscriptome revealed that the majority (18 out of the top 20 predicted KEGG pathways) of the salivary gland contig sequences match proteins involved in metabolism. We identified several genes likely to be involved in detoxification and inhibition of plant defense responses including aldehyde dehydrogenase, metalloprotease, glucose oxidase, glucose dehydrogenase, and regucalcin. We also identified several genes that may play a role in the extra-oral digestion of plant structural tissues including β-glucosidase and pectin lyase; and the extra-oral digestion of sugars, including α-amylase, maltase, sucrase, and α-glucosidase. This is the first analysis of a sialotranscriptome for any Thysanopteran species and it provides a foundational tool to further our understanding of how thrips interact with their plant hosts and the viruses they

Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy.

PubMed

Lang, Brian Hung-Hin; Wong, Carlos K H; Hung, Hing Tsun; Wong, Kai Pun; Mak, Ka Lun; Au, Kin Bun

2017-01-01

Because the fluorescent light intensity on an indocyanine green fluorescence angiography reflects the blood perfusion within a focused area, the fluorescent light intensity in the remaining in situ parathyroid glands may predict postoperative hypocalcemia risk after total thyroidectomy. Seventy patients underwent intraoperative indocyanine green fluorescence angiography after total thyroidectomy. Any parathyroid glands with a vascular pedicle was left in situ while any parathyroid glands without pedicle or inadvertently removed was autotransplanted. After total thyroidectomy, an intravenous 2.5 mg indocyanine green fluorescence angiography was given and real-time fluorescent images of the thyroid bed were recorded using the SPY imaging system (Novadaq, Ontario, Canada). The fluorescent light intensity of each indocyanine green fluorescence angiography as well as the average and greatest fluorescent light intensity in each patient were calculated. Postoperative hypocalcemia was defined as adjusted calcium <2.00 mmol/L within 24 hours. The fluorescent light intensity between discolored and normal-looking indocyanine green fluorescence angiographies was similar (P = .479). No patients with a greatest fluorescent light intensity >150% developed postoperative hypocalcemia while 9 (81.8%) patients with a greatest fluorescent light intensity ≤150% did. Similarly, no patients with an average fluorescent light intensity >109% developed PH while 9 (30%) with an average fluorescent light intensity ≤109% did. The greatest fluorescent light intensity was more predictive than day-0 postoperative hypocalcemia (P = .027) and % PTH drop day-0 to 1 (P < .001). Indocyanine green fluorescence angiography is a promising operative adjunct in determining residual parathyroid glands function and predicting postoperative hypocalcemia risk after total thyroidectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Adrenal Gland Cancer

MedlinePlus

... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

Development of the thyroid gland.

PubMed

Nilsson, Mikael; Fagman, Henrik

2017-06-15

Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland - the only source of thyroid hormones in the body - develops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed. © 2017. Published by The Company of Biologists Ltd.

C/EBPα and C/EBPβ Are Required for Sebocyte Differentiation and Stratified Squamous Differentiation in Adult Mouse Skin

PubMed Central

House, John S.; Zhu, Songyun; Ranjan, Rakesh; Linder, Keith; Smart, Robert C.

2010-01-01

C/EBPα and C/EBPβ are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPα and C/EBPβ in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPα or C/EBPβ alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPα and C/EBPβ in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPα and C/EBPβ in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPα and C/EBPβ are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal. PMID:20352127

C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin.

PubMed

House, John S; Zhu, Songyun; Ranjan, Rakesh; Linder, Keith; Smart, Robert C

2010-03-23

C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.

Odorous secretions in anurans: morphological and functional assessment of serous glands as a source of volatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae).

PubMed

Brunetti, Andrés E; Hermida, Gladys N; Iurman, Mariana G; Faivovich, Julián

2016-03-01

Serous (granular or venom) glands occur in the skin of almost all species of adult amphibians, and are thought to be the source of a great diversity of chemical compounds. Despite recent advances in their chemistry, odorous volatile substances are compounds that have received less attention, and until now no study has attempted to associate histological data with the presence of these molecules in amphibians, or in any other vertebrate. Given the recent identification of 40 different volatile compounds from the skin secretions of H. pulchellus (a treefrog species that releases a strong odour when handled), we examined the structure, ultrastructure, histochemistry, and distribution of skin glands of this species. Histological analysis from six body regions reveals the presence of two types of glands that differ in their distribution. Mucous glands are homogeneously distributed, whereas serous glands are more numerous in the scapular region. Ultrastructural results indicate that electron-translucent vesicles observed within granules of serous glands are similar to those found in volatile-producing glands from insects and also with lipid vesicles from different organisms. Association among lipids and volatiles is also evidenced from chemical results, which indicate that at least some of the volatile components in H. pulchellus probably originate within the metabolism of fatty acids or the mevalonate pathway. As odorous secretions are often considered to be secreted under stress situations, the release of glandular content was assessed after pharmacological treatments, epinephrine administrated in vivo and on skin explants, and through surface electrical stimulation. Serous glands responded to all treatments, generally through an obvious contraction of myoepithelial cells that surround their secretory portion. No response was observed in mucous glands. Considering these morpho-functional results, along with previous identification of volatiles from H. pulchellus and H

Dysregulation of the Bmi-1/p16Ink4a pathway provokes an aging-associated decline of submandibular gland function

PubMed Central

Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto-Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo

2015-01-01

Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16Ink4a. Therefore, dysregulation of the Bmi-1/p16Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16Ink4a pathway occurs during aging in vivo. Using real-time in vivo imaging of p16Ink4a expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly. PMID:25832744

Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance.

PubMed

Rath, Martin F; Rohde, Kristian; Klein, David C; Møller, Morten

2013-06-01

The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell.

Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance

PubMed Central

Rath, Martin F.; Rohde, Kristian; Klein, David C.; Møller, Morten

2012-01-01

The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell. PMID:23076630

Novel function of lipids as a pheromone from the Harderian gland of golden hamster

PubMed Central

Seyama, Yousuke; Uchijima, Yasunobu

2007-01-01

Sexual diversity of ADG in Harderian gland of golden hamster was demonstrated on TLC. Female ADG contained iso- and anteiso-branched acyl and alkyl components, but male ADG contained only straight chain ones, which suggested the hormonal control of the expression of acyl-CoA dehydrogenases in the catabolism of BCAA. Acyl-CoA dehydrogenases were not expressed in the absence of testosterone, and then isovaleryl-CoA, 2-methylbutyryl-CoA, and isobutyryl-CoA accumulated, and acted as primers for the synthesis of iso- and anteiso-branched fatty acids. The incorporation of [U-14C] leucine into lipids was monitored by TLC. The cholesterol fraction was labeled in males but not in female, which means that cholesterol was not produced from BCAA in female gland due to the lack of expression of acyl-CoA dehydrogenases. We monitored the behavior of male hamsters toward female gland lipids, and found slightly greater attractiveness in female ones than that in male ones although the difference was not significant. Considering the lifestyle of golden hamster in nature, we propose a hypothesis that the lipids from the Harderian gland of golden hamster serve as a pheromone to declare their territory and to seek the mate with good congeniality. PMID:24019586

Melatonin, The Pineal Gland and Circadian Rhythms

DTIC Science & Technology

1992-04-30

physiological rhythms including locomotion, sleep/wake, thermoregulation , car- diovascular function and many endocrine processes. Among the rhythms under SCN...control of a wide array of behavioral and physiological rhythms including locomotion, sleep/wake, thermoregulation , cardiovascular function and many... reptiles and birds, overt rhythmicity results from the integration of multiple circadian oscillators within the pineal gland, eyes and the presumed

Silks produced by insect labial glands

PubMed Central

Sutherland, Tara

2008-01-01

Insect silks are secreted from diverse gland types; this chapter deals with the silks produced by labial glands of Holometabola (insects with pupa in their life cycle). Labial silk glands are composed of a few tens or hundreds of large polyploid cells that secrete polymerizing proteins which are stored in the gland lumen as a semi-liquid gel. Polymerization is based on weak molecular interactions between repetitive amino acid motifs present in one or more silk proteins; cross-linking by disulfide bonds may be important in the silks spun under water. The mechanism of long-term storage of the silk dope inside the glands and its conversion into the silk fiber during spinning is not fully understood. The conversion occurs within seconds at ambient temperature and pressure, under minimal drawing force and in some cases under water. The silk filament is largely built of proteins called fibroins and in Lepidoptera and Trichoptera coated by glue-type proteins known as sericins. Silks often contain small amounts of additional proteins of poorly known function. The silk components controlling dope storage and filament formation seem to be conserved at the level of orders, while the nature of polymerizing motifs in the fibroins, which determine the physical properties of silk, differ at the level of family and even genus. Most silks are based on fibroin β-sheets interrupted with other structures such as α-helices but the silk proteins of certain sawflies have predominantly a collagen-like or polyglycine II arrangement and the silks of social Hymenoptera are formed from proteins in a coiled coil arrangement. PMID:19221523

mRNAs for PRPs, statherin, and histatins in von Ebner's gland tissues.

PubMed

Azen, E A; Hellekant, G; Sabatini, L M; Warner, T F

1990-11-01

A search was made for expression of genes for proline-rich proteins (PRPs) and other salivary-type proteins, including statherin and histatins, in taste-bud tissues of mice and primates because of previous genetic findings in mice (Azen et al., 1986) that Prp and taste genes for certain bitter substances are either the same or closely linked. Taste-bud tissues and other tissues were tested for specific mRNAs with labeled DNA probes by Northern blotting and in situ hybridization. It was found that PRP mRNAs were present in von Ebner's glands of mice and macaques, and that there was a much greater degree of PRP mRNA induction in mouse parotid (16-fold) than in von Ebner's gland (two-fold) after in vivo isoproterenol stimulation. This difference may be due, in part, to differences in autonomic nerve innervation. Statherin and histatin mRNAs were found in macaque taste-bud tissues containing von Ebner's gland, and statherin protein was found in human von Ebner's gland by immunohistochemistry. The finding of PRP gene expression in von Ebner's gland, whose secretions have been suggested to play a role in taste stimulation, adds further support to a possible function of PRPs in bitter tasting. The possible functions of statherin and histatins in von Ebner's gland secretions may be related to statherin's regulation of salivary calcium and histatins' antibacterial and antifungal properties.

Morphological Changes in Skin Glands During Development in Rhinella Arenarum (Anura: Bufonidae).

PubMed

Regueira, Eleonora; Dávila, Camila; Hermida, Gladys N

2016-01-01

Avoiding predation is critical to survival of animals; chemical defenses represent a common strategy among amphibians. In this study, we examined histologically the morphology of skin glands and types of secretions related to chemical skin defense during ontogeny of Rhinella arenarum. Prior to metamorphic climax the epidermis contains typical bufonid giant cells producing a mucous substance supposedly involved in triggering a flight reaction of the tadpole school. An apical layer of alcianophilic mucus covers the epidermis, which could produce the unpleasant taste of bufonid tadpoles. Giant cells disappear by onset of metamorphic climax, when multicellular glands start developing, but the apical mucous layer remains. By the end of climax, neither the granular glands of the dorsum nor the parotoid regions are completely developed. Conversely, by the end of metamorphosis the mucous glands are partially developed and secrete mucus. Adults have at least three types of granular glands, which we designate type A (acidophilic), type B (basophilic) and ventral (mucous). Polymorphic granular glands distribute differently in the body: dorsal granular glands between warts and in the periphery of parotoids contain protein; granular glands of big warts and in the central region of parotoids contain catecholamines, lipids, and glycoconjugates, whereas ventral granular glands produce acidic glycoconjugates. Mucous glands produce both mucus and proteins. Results suggest that in early juveniles the chemical skin defense mechanisms are not functional. Topographical differences in adult skin secretions suggest that granular glands from the big warts in the skin produce similar toxins to the parotoid glands. © 2015 Wiley Periodicals, Inc.

[MORPHO-FUNCTIONAL CHARACTERISTIC OF THE THYROID GLAND AFTER ADMINISTRATION OF COPPER NANOPARTICLES].

PubMed

Polyakova, V S; Sizova, Ye A; Miroshnikov, S A; Notova, S V; Zavaleyeva, S M

2015-01-01

The study was conducted on 15 male Wistar rats, which were injected intramuscularly with copper nanoparticle lyosols at a dose of 2.0 mg/kg body weight once a week for 3 months. Thyroid gland was removed 7 days after the last injection and was studied using histological, morphometric and immunohistochemical methods (demonstration of Ki-67 and caspase-3). Animals of the control group (n = 15) were administered distilled water at the same time intervals. It was found that after 1, 2, 3 and 4 injections of copper nanoparticles, the thyroid gland contained an increased number of large cyst-like follicles, while the average thyrocyte height of and the volume of their nuclei were reduced, which indicate a decline in hormone production. After 12 injections of copper nanoparticles, the hyperplastic thyroid gland demonstrated small follicles lined with columnar epithelium, which contained no or small amount of the colloid. The number of mitotically dividing thyrocytes was increased. Parafollicular cells demonstrated an apoptotic dominant. Morphological data suggest goitrogenic effect of multiple doses of copper nanopartides. The data received indicating the readiness of the thyroid cells to the programmed death and its possible depression (absence of signs of thyrocyte apoptosis) at different stages of the experiment confirm the modulating effect of copper on apoptosis.

Exploring the Predisposition of the Asian Eye to Development of Dry Eye.

PubMed

Craig, Jennifer P; Wang, Michael T M; Kim, Dabin; Lee, Jung Min

2016-07-01

To investigate the influence of eyelid shape on tear film quality, ocular surface characteristics and dry eye symptomatology by comparing Asian and Caucasian populations. Seventy-four age-matched participants were recruited in a cross-sectional study. Participants were classified into Asian single lid (ASL), Asian double lid (ADL), and Caucasian double lid (CDL) groups. Dry eye symptomatology, ocular surface characteristics, and tear film quality were evaluated in a single clinical session. Meibomian gland dropout was significantly greater in both the ASL and ADL groups than in the CDL group (all P<.05). A greater proportion of ASL and ADL participants exhibited incomplete blinking than CDL patients (all P<.05). There were no significant differences in tear film quality and dry eye symptomatology between the three groups (all P>.05). Exposed ocular surface area, lissamine green staining, and lid wiper epitheliopathy were significantly greater in the ADL group compared to the CDL group (all P<.05). The CDL group displayed significantly greater anterior blepharitis and lid telangiectasia grades compared to both ASL and ADL groups (all P<.05). A higher degree of meibomian gland dropout and incomplete blinking was observed in both Asian groups compared to the Caucasian group, potentially predisposing these groups to dry eye. Copyright © 2016 Elsevier Inc. All rights reserved.

The accessory parotid gland and facial process of the parotid gland on computed tomography

PubMed Central

Ahn, Dongbin; Yeo, Chang Ki; Han, Soon Yong

2017-01-01

The purpose of this study was to determine the incidence of an anterior extension of the parotid gland, such as an accessory parotid gland (APG) or facial process (FP) and to evaluate its characteristics on computed tomography (CT) scans. We reviewed CT scans of 1,600 parotid glands from 800 patients. An APG on CT was defined as a soft-tissue mass of the same density as the main parotid gland, located at the anterior part of the main parotid gland, and completely separate from the main parotid gland. An FP was defined as a lobe of the parotid gland protruding anteriorly over the anterior edge of the ramus of the mandible on CT and showing continuity with the main gland. The overall incidence rates and characteristics of APGs and FPs were evaluated according to age, sex, and side. The incidence rates of APGs and FPs were 10.2% (163/1,600) and 28.3% (452/1,600), respectively. The mean size of an APG was 15.8 mm × 5.0 mm and the mean distance from the main parotid gland was 10.5 mm. The FP reached anteriorly between the anterior edge of the mandibular ramus and the anterior border of the masseter muscle in 405 (89.6%) cases, while it extended over the anterior border of the masseter muscle in 47 (10.4%) cases. The incidence rates of APGs and FPs decreased and increased, respectively, with increasing age, showing significant linear correlations. However, the incidence of an anterior extension of the parotid gland (either an APG or an FP) was similar across all age groups. The present study showed that CT might be helpful in identifying anterior extensions of the parotid gland including APGs and FPs. The anatomical information gained from this study contributes to a better understanding of APGs and FPs and how their incidence changes with age. PMID:28915265

Relationship between histology, development and tumorigenesis of mammary gland in female rat

PubMed Central

LÍŠKA, Ján; BRTKO, Július; DUBOVICKÝ, Michal; MACEJOVÁ, Dana; KISSOVÁ, Viktória; POLÁK, Štefan; UJHÁZY, Eduard

2015-01-01

The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

Descartes and the pineal gland in animals: a frequent misinterpretation.

PubMed

Finger, S

1995-01-01

René Descartes presented a number of reasons for his choice of the pineal gland as a logical place for the soul to interact with the physical machinery of the body. It is often stated that one of his reasons was that he believed animals do not have pineal glands, whereas humans alone possess a soul and this small structure. This is a misinterpretation of Descartes. The philosopher knew that barnyard and other animals possess pineal glands, having seen this with his own eyes. His point was that the pineal is unique in humans only because of a special function - acting as the seat for the rational soul.

Salivary Gland Cancer

MedlinePlus

... contains antibodies that can kill germs. Salivary gland cancer is a type of head and neck cancer. It is rare. It may not cause any ... pain in your face Doctors diagnose salivary gland cancer using a physical exam, imaging tests, and a ...

Msx-1 and Msx-2 in mammary gland development.

PubMed

Satoh, Kennichi; Ginsburg, Erika; Vonderhaar, Barbara K

2004-04-01

Homeobox genes do not generally function alone to determine cell fate and morphogenesis. Rather it is the distinct combination of various members of the homeobox family of genes and their spatiotemporal patterns of expression that determine cell identity and function. Functional redundancy often makes it difficult to clearly discern the role of any one given homeobox gene. The roles that Msx1 and Msx2 play in branching morphogenesis of the mammary gland are only now becoming more evident. Many signaling pathways and transcription factors are implicated in how these homeobox genes correctly determine the morphological development of the gland. Overexpression of Msx1 and Msx2 may also be involved in tumorigenesis. Additional studies are needed to elucidate the roles of these genes in both breast development and cancer.

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

PubMed

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

Molecular Mechanism of Pancreatic and Salivary Glands Fluid and HCO3− Secretion

PubMed Central

Lee, Min Goo; Ohana, Ehud; Park, Hyun Woo; Yang, Dongki; Muallem, Shmuel

2013-01-01

Fluid and HCO3− secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3− secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren’s syndrome and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3− secretion, in particular by secretory glands. Fluid and HCO3− secretion by secretory glands is a two step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl− and secrete HCO3−. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete small amount of NaCl-rich fluid, while the duct absorbs the Cl− and secretes HCO3− and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO3− secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that contains high concentrations of Na+ and Cl− and fluid secretion is mediated by active Cl− secretion. The salivary glands duct absorbs both the Na+ and Cl− and secretes K+ and HCO3−. In this review, we focus on the molecular mechanism of fluid and HCO3− secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and point the differences to meet glands specific secretions. PMID:22298651

Chemical and behavioral studies of femoral gland secretions in iguanid lizards.

PubMed

Alberts, A C

1993-01-01

Comparative studies on the chemistry and behavioral significance of femoral gland secretions in desert iguanas (Dipsosaurus dorsalis) and green iguanas (Iguana iguana) are reviewed. Field and laboratory studies suggest that femoral gland secretions function in conspecific recognition and range marking. In desert iguanas, secretions are of low volatility and may be detected initially using long-range ultraviolet visual cues. In contrast, green iguana secretions contain a diversity of volatile lipids and appear to be localized by chemoreception. Interspecific differences in femoral gland chemistry may reflect adaptations to the diverse climatic conditions of arid desert and tropical forest environments.

Gross morphology and ultrastructure of salivary glands of the mute cicada Karenia caelatata Distant (Hemiptera: Cicadoidea).

PubMed

Zhong, Hai-ying; Wei, Cong; Zhang, Ya-lin

2013-02-01

Salivary glands of the cicada Karenia caelatata Distant were investigated using light microscopy and transmission electron microscopy. The salivary glands are paired structures and consist of principal glands and accessory glands. The principal gland is subdivided into anterior lobe and posterior lobe; the former contains about 34-39 long digitate lobules, while the latter contains approximately 30-33 long digitate lobules and 13-22 short digitate lobules. These short digitate lobules, about one fifth or sixth as long as the long digitate lobules, locate at the base of the long digitate lobules of posterior lobe. All of these digitate lobules vary in size, disposition, length and shape. The anterior lobe and the posterior lobe are connected by an anterior-posterior duct. Two efferent salivary ducts, which connect with the posterior lobe, fuse to form a common duct. The accessory gland is composed of three parts: a greatly tortuous and folded accessory salivary tube, a circlet of gular gland constituting of several acini of the same size, and a non-collapsible accessory salivary duct. The digitate lobules and gular glands possess secretory cells containing abundant secretory granules vary in size, shape, and electron density, as might indicate different materials are synthesized in different secretory regions. The anterior-posterior duct lines with a player of cuticular lining, and cells beneath the cuticular lining lack of basal infoldings, as suggests the duct serves just to transport secretions. The accessory salivary duct is lined with cuticular lining; cells of the duct have well developed basal infoldings associated with abundant mitochondria, as probably suggests the duct is a reabsorptive region of ions. The cells of the accessory salivary tube possess deep basal infoldings and well developed apical dense microvilli, indicating the cells of the tube are secretory in function. Concentric lamellar structures and a peculiar structure with abundant membrane

Pituitary gland in psychiatric disorders: a review of neuroimaging findings.

PubMed

Atmaca, Murad

2014-08-01

In this paper, it was reviewed neuroimaging results of the pituitary gland in psychiatric disorders, particularly schizophrenia, mood disorders, anxiety disorders, and somatoform disorders. The author made internet search in detail by using PubMed database including the period between 1980 and 2012 October. It was included in the articles in English, Turkish and French languages on pituitary gland in psychiatric disorders through structural or functional neuroimaging results. After searching mentioned in the Methods section in detail, investigations were obtained on pituitary gland neuroimaging in a variety of psychiatric disorders. There have been so limited investigations on pituitary neuroimaging in psychiatric disorders including major psychiatric illnesses like schizophrenia and mood disorders. Current findings are so far from the generalizability of the results. For this reason, it is required to perform much more neuroimaging studies of pituitary gland in all psychiatric disorders to reach the diagnostic importance of measuring it.

The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

PubMed Central

Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.

2015-01-01

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318

In Vivo Evidence for Epidermal Growth Factor Receptor (EGFR)-mediated Release of Prolactin from the Pituitary Gland

PubMed Central

Dahlhoff, Maik; Blutke, Andreas; Wanke, Rüdiger; Wolf, Eckhard; Schneider, Marlon R.

2011-01-01

Members of the epidermal growth factor receptor (EGFR/ERBB) system are essential local regulators of mammary gland development and function. Emerging evidence suggests that EGFR signaling may also influence mammary gland activity indirectly by promoting the release of prolactin from the pituitary gland in a MAPK and estrogen receptor-α (ERα)-dependent manner. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) causes a lactating-like phenotype in the mammary gland of virgin female mice including the major hallmarks of lactogenesis. BTC transgenic (BTC-tg) females showed reduced levels of prolactin in the pituitary gland and increased levels of the hormone in the circulation. Furthermore, treatment of BTC-tg females with bromocriptine, an inhibitor of prolactin secretion, blocked the development of the lactation-like phenotype, suggesting that it is caused by central release of prolactin rather than by local actions of BTC in the mammary gland. Introduction of the antimorphic Egfr allele Wa5 also blocked the appearance of the mammary gland alterations, revealing that the phenotype is EGFR-dependent. We detected an increase in MAPK activity, but unchanged phosphorylation of ERα in the pituitary gland of BTC-tg females as compared with control mice. These results provide the first functional evidence in vivo for a role of the EGFR system in regulating mammary gland activity by modulating prolactin release from the pituitary gland. PMID:21914800

PAR-2 receptor-induced effects on human eccrine sweat gland cells.

PubMed

L Bovell, Douglas; Kofler, Barbara; Lang, Roland

2009-01-01

Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

Differences in the ribosomes prepared from lactating and non-lactating bovine mammary gland

PubMed Central

Herrington, M. D.; Hawtrey, A. O.

1971-01-01

1. Ribosomes prepared from bovine lactating mammary gland are able to synthesize protein, whereas similar preparations from non-lactating glands are not. Washing the ribosome suspensions through a medium containing 0.5m-ammonium chloride enhanced their ability to incorporate phenylalanine into polyphenylalanine. 2. Ribosomes isolated from non-lactating bovine mammary gland, in contrast with those from rat liver and lactating mammary gland, contained significant amounts of extraneous nucleases. These enzymes could be removed by washing with a medium A buffer containing 0.5m-ammonium chloride. 3. Only those ribosomes from functionally active tissues were able to bind polyuridylic acid and phenylalanyl-tRNA. PMID:5165653

Oxytocin in corticosterone-induced chronic stress model: Focus on adrenal gland function.

PubMed

Stanić, Dušanka; Plećaš-Solarović, Bosiljka; Mirković, Duško; Jovanović, Predrag; Dronjak, Slađana; Marković, Bojan; Đorđević, Tea; Ignjatović, Svetlana; Pešić, Vesna

2017-06-01

Chronic stress conditions can lead to considerable and extensible changes in physiological and psychological performances, and in emergence of risk for various somatic diseases. On the other hand, the neuropeptide oxytocin is reported to increase the resistance of the organism to stress and modulate activity of autonomic nervous system. Chronic corticosterone administration is used as a rat model for a state observed in terms of chronic stress exposure, when negative feedback mechanism of hypothalamus-pituitary-adrenal axis activity is disrupted. In our study, we aimed to investigate whether chronic administration of oxytocin (10 IU/400μL/day for 14days, s.c.) influenced adrenal gland morphology and activity in adult male Wistar rats during long-term corticosterone administration via drinking water (100mg/L for 21days). We examined the influence of treatments on the levels of adrenal gland hormones, corticosterone, adrenaline and noradrenaline, as well as their response to an acute stress challenge evoked by 15-min forced swimming. In addition, the expression of two main monoamine transporters, the noradrenaline transporter (NAT) and vesicular monoamine transporter 2 (VMAT2) in adrenal medulla was measured in the rats exposed to acute stress. Our results showed that oxytocin treatment prevented corticosterone-induced decrease in body weight gain, attenuated adrenal gland atrophy by increasing glandular weight, and the area of the zona fasciculate and reticularis. Chronic corticosterone intake blunted the response of all measured hormones to acute stress, whereas concomitant oxytocin treatment reversed adrenaline and noradrenaline response to acute stress. Furthermore, in adrenal medulla, oxytocin produced significant vasodilatation and stimulated expression of both catecholamine transporters detected both on mRNA and protein level. Our data suggest that oxytocin, by reducing atrophy of adrenal gland, and by increasing catecholamine storage capacity, may be

Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

PubMed

Hoang, Don; Broer, Niclas; Sosa, Julie A; Abitbol, Nathalie; Yao, Xiaopan; Li, Fangyong; Rivera-Molina, Felix; Toomre, Derek K; Roman, Sanziana A; Sue, Gloria; Kim, Samuel; Li, Alexander Y; Callender, Glenda G; Simpson, Christine; Narayan, Deepak

2017-12-01

We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

Salivary Gland Secretion.

ERIC Educational Resources Information Center

Dorman, H. L.; And Others

1981-01-01

Describes materials and procedures for an experiment utilizing a live dog to demonstrate: (1) physiology of the salivary gland; (2) parasympathetic control of the salivary gland; (3) influence of varying salivary flow rates on sodium and potassium ions, osmolarity and pH; and (4) salivary secretion as an active process. (DS)

Epigenetic Modifications Unlock the Milk Protein Gene Loci during Mouse Mammary Gland Development and Differentiation

PubMed Central

Rijnkels, Monique; Freeman-Zadrowski, Courtneay; Hernandez, Joseph; Potluri, Vani; Wang, Liguo; Li, Wei; Lemay, Danielle G.

2013-01-01

Background Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation. Methodology/Principal Findings Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization. Conclusions/Significance A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the

Parotid Gland Sparing With Helical Tomotherapy in Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voordeckers, Mia, E-mail: mia.voordeckers@uzbrussel.be; Farrag, Ashraf; Assiut University

Purpose: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment. Methods and Materials: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: {>=}95% of the dose must be delivered to {>=}95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologicmore » lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H and N35). Results: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H and N35. Most items improved in time, and some reached baseline values 18 months after treatment. Conclusion: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the

The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio).

PubMed

Laurà, Rosaria; Magnoli, Domenico; Zichichi, Rosalia; Guerrera, Maria Cristina; De Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

2012-03-01

The zebrafish pineal gland plays a fundamental role in the regulation of the circadian rhythm through the melatonin secretion. The pinealocytes, also called photoreceptive cells, are considered the morphofunctional unit of pineal gland. In literature, the anatomical features, the cellular characteristics, and the pinealocytes morphology of zebrafish pineal gland have not been previously described in detail. Therefore, this study was undertaken to analyze the structure and ultrastructure, as well as the immunohistochemical profile of the zebrafish pineal gland with particular reference to the pinealocytes. Here, we demonstrated, using RT-PCR, immunohistochemistry and transmission electron microscopy, the expression of the mRNA for rhodopsin in the pineal gland of zebrafish, as well as its cellular localization exclusively in the pinealocytes of adult zebrafish. Moreover, the ultrastructural observations demonstrated that the pinealocytes were constituted by an outer segment with numerous lamellar membranes, an inner segment with many mitochondria, and a basal pole with the synapses. Our results taken together demonstrated a central role of zebrafish pinealocytes in the control of pineal gland functions. Copyright © 2011 Wiley Periodicals, Inc.

Rhodopsin Kinase Activity in the Mammalian Pineal Gland and Other Tissues

NASA Astrophysics Data System (ADS)

Somers, Robert L.; Klein, David C.

1984-10-01

Rhodopsin kinase, an enzyme involved in photochemical transduction in the retina, has been found in the mammalian pineal gland in amounts equal to those in the retina; other tissues had 7 percent of this amount, or less. This finding suggests that, in mammals, rhodopsin kinase functions in the pineal gland and other tissues to phosphorylate rhodopsin-like integral membrane receptors and is thereby involved in signal transduction.

Lectin histochemistry of the interdigital gland in the Japanese serow (Capricornis crispus) in winter.

PubMed Central

Atoji, Y; Suzuki, Y; Sugimura, M

1988-01-01

The interdigital gland of the Japanese serow was examined by histological and lectin histochemical techniques. The gland is composed of a thin-walled pouch and a duct. Both regions contain sebaceous and apocrine glands, but the development of each component was significantly less marked than those of the skin in the region. In particular, only a small amount of sebaceous and apocrine glandular elements was found in the pouch, although they were more abundant in the duct. Histochemical staining of the sebaceous and apocrine glands showed similar reactions to six lectins except for UEA in the interdigital gland and digital surface skin. UEA reacted with the apocrine part of the interdigital gland, but not with the gland in the digital surface skin. In addition, tubules in the apocrine gland revealed eight different staining patterns with UEA. These stainings possibly represent a cyclic activity of glandular tubules and suggest that the apocrine portion of the interdigital gland has a different function from that of the body skin. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:3254889

Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes.

PubMed

Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Pontiggia, Luca; Braziulis, Erik; Schiestl, Clemens; Hendriks, Bart; Eichhoff, Ossia M; Widmer, Daniel S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2013-02-01

Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added human melanocytes to eccrine sweat gland cells to let them develop into an epidermal analog in vivo. The interaction between melanocytes and sweat gland-derived keratinocytes was investigated. The following results were gained: (1) macroscopically, a pigmentation of the substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the development of a multilayered, stratified epidermis with melanocytes distributed evenly throughout the basal layer; (3) melanocytic dendrites projected to suprabasal layers; and (4) melanin was observed to be integrated into former eccrine sweat gland cells. These skin substitutes were similar or equal to skin substitutes cultured from human epidermal keratinocytes. The only differences observed were a delay in pigmentation and less melanin uptake. These data suggest that eccrine sweat gland cells can form a functional epidermal melanin unit, thereby providing striking evidence that they can assume one of the most characteristic keratinocyte properties.

Salivary gland diseases in children

PubMed Central

Iro, Heinrich; Zenk, Johannes

2014-01-01

Salivary gland diseases in children are rare, apart from viral-induced diseases. Nevertheless, it is essential for the otolaryngologist to recognize these uncommon findings in children and adolescents and to diagnose and initiate the proper treatment. The present work provides an overview of the entire spectrum of congenital and acquired diseases of the salivary glands in childhood and adolescence. The current literature was reviewed and the results discussed and summarized. Besides congenital diseases of the salivary glands in children, the main etiologies of viral and bacterial infections, autoimmune diseases and tumors of the salivary glands were considered. In addition to the known facts, new developments in diagnostics, imaging and therapy, including sialendoscopy in obstructive diseases and chronic recurrent juvenile sialadenitis were taken into account. In addition, systemic causes of salivary gland swelling and the treatment of sialorrhoea were discussed. Although salivary gland diseases in children are usually included in the pathology of the adult, they differ in their incidence and some­times in their symptoms. Clinical diagnostics and especially the surgical treatment are influenced by a stringent indications and a less invasive strategy. Due to the rarity of tumors of the salivary glands in children, it is recommended to treat them in a specialized center with greater surgical experience. Altogether the knowledge of the differential diagnoses in salivary gland diseases in children is important for otolaryngologists, to indicate the proper therapeutic approach. PMID:25587366

Standards of ultrasound imaging of the adrenal glands

PubMed Central

Jakubowski, Wiesław S.; Dobruch-Sobczak, Katarzyna; Kasperlik-Załuska, Anna A.

2015-01-01

Adrenal glands are paired endocrine glands located over the upper renal poles. Adrenal pathologies have various clinical presentations. They can coexist with the hyperfunction of individual cortical zones or the medulla, insufficiency of the adrenal cortex or retained normal hormonal function. The most common adrenal masses are tumors incidentally detected in imaging examinations (ultrasound, tomography, magnetic resonance imaging), referred to as incidentalomas. They include a range of histopathological entities but cortical adenomas without hormonal hyperfunction are the most common. Each abdominal ultrasound scan of a child or adult should include the assessment of the suprarenal areas. If a previously non-reported, incidental solid focal lesion exceeding 1 cm (incidentaloma) is detected in the suprarenal area, computed tomography or magnetic resonance imaging should be conducted to confirm its presence and for differentiation and the tumor functional status should be determined. Ultrasound imaging is also used to monitor adrenal incidentaloma that is not eligible for a surgery. The paper presents recommendations concerning the performance and assessment of ultrasound examinations of the adrenal glands and their pathological lesions. The article includes new ultrasound techniques, such as tissue harmonic imaging, spatial compound imaging, three-dimensional ultrasound, elastography, contrast-enhanced ultrasound and parametric imaging. The guidelines presented above are consistent with the recommendations of the Polish Ultrasound Society. PMID:26807295

A Single Injection of Interleukin-1 Induces Reversible Aqueous-tear Deficiency, Lacrimal Gland Inflammation, and Acinar and Ductal Cell Proliferation

PubMed Central

Zoukhri, Driss; Macari, Elizabeth; Kublin, Claire L.

2011-01-01

Emerging studies from our laboratory demonstrate that interleukin-1 (IL-1) family members play a major role in impairing lacrimal gland functions. Here we have extended our investigations to observe the effects of IL-1 on aqueous tear production, lacrimal gland secretion, lacrimal gland histology, and acinar and ductal cell proliferation. We demonstrate that a single injection of IL-1 into the lacrimal glands inhibited neurally- as well as agonist-induced protein secretion resulting in decreased tear output. Meanwhile, IL-1 injection induced a severe, but reversible (7–13 days), inflammatory response that led to destruction of lacrimal gland acinar epithelial cells. Finally, we demonstrate that as the inflammatory response subsided and lacrimal gland secretion and tear production returned to normal levels, there was increased proliferation of acinar and ductal epithelial cells. Our work uncovers novel effects of IL-1 on lacrimal gland functions and the potential regenerative capacity of the mouse lacrimal gland. PMID:17362931

Promising Gene Therapeutics for Salivary Gland Radiotoxicity

PubMed Central

Nair, Renjith Parameswaran; Sunavala-Dossabhoy, Gulshan

2017-01-01

More than 0.5 million new cases of head and neck cancer are diagnosed worldwide each year, and approximately 75% of them are treated with radiation alone or in combination with other cancer treatments. A majority of patients treated with radiotherapy develop significant oral off-target effects because of the unavoidable irradiation of normal tissues. Salivary glands that lie within treatment fields are often irreparably damaged and a decline in function manifests as dry mouth or xerostomia. Limited ability of the salivary glands to regenerate lost acinar cells makes radiation-induced loss of function a chronic problem that affects the quality of life of the patients well beyond the completion of radiotherapy. The restoration of saliva production after irradiation has been a daunting challenge, and this review provides an overview of promising gene therapeutics that either improve the gland’s ability to survive radiation insult, or alternately, restore fluid flow after radiation. The salient features and shortcomings of each approach are discussed. PMID:28286865

Function of the Membrane Water Channel Aquaporin-5 in the Salivary Gland

PubMed Central

Matsuzaki, Toshiyuki; Susa, Taketo; Shimizu, Kinue; Sawai, Nobuhiko; Suzuki, Takeshi; Aoki, Takeo; Yokoo, Satoshi; Takata, Kuniaki

2012-01-01

The process of saliva production in the salivary glands requires transepithelial water transfer from the interstitium to the acinar lumen. There are two transepithelial pathways: the transcellular and paracellular. In the transcellular pathway, the aquaporin water channels induce passive water diffusion across the membrane lipid bilayer. It is well known that aquaporin-5 (AQP5) is expressed in the salivary glands, in which it is mainly localized at the apical membrane of the acinar cells. This suggests the physiological importance of AQP5 in transcellular water transfer. Reduced saliva secretion under pilocarpine stimulation in AQP5-null mice compared with normal mice further indicates the importance of AQP5 in this process, at least in stimulated saliva secretion. Questions remain therefore regarding the role and importance of AQP5 in basal saliva secretion. It has been speculated that there would be some short-term regulation of AQP5 such as a trafficking mechanism to regulate saliva secretion. However, no histochemical evidence of AQP5-trafficking has been found, although some of biochemical analyses suggested that it may occur. There are no reports of human disease caused by AQP5 mutations, but some studies have revealed an abnormal subcellular distribution of AQP5 in patients or animals with xerostomia caused by Sjögren’s syndrome and X-irradiation. These findings suggest the possible pathophysiological importance of AQP5 in the salivary glands. PMID:23209334

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

PubMed

Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

2017-01-16

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

PubMed

Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-03-15

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

PubMed Central

Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-01-01

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.

PubMed

Collaco, Anne M; Jakab, Robert L; Hoekstra, Nadia E; Mitchell, Kisha A; Brooks, Amos; Ameen, Nadia A

2013-08-01

The Brunner's glands of the proximal duodenum exert barrier functions through secretion of glycoproteins and antimicrobial peptides. However, ion transporter localization, function, and regulation in the glands are less clear. Mapping the subcellular distribution of transporters is an important step toward elucidating trafficking mechanisms of fluid transport in the gland. The present study examined 1) changes in the distribution of intestinal anion transporters and the aquaporin 5 (AQP5) water channel in rat Brunner's glands following second messenger activation and 2) anion transporter distribution in Brunner's glands from healthy and disease-affected human tissues. Cystic fibrosis transmembrane conductance regulator (CFTR), AQP5, sodium-potassium-coupled chloride cotransporter 1 (NKCC1), sodium-bicarbonate cotransporter (NBCe1), and the proton pump vacuolar ATPase (V-ATPase) were localized to distinct membrane domains and in endosomes at steady state. Carbachol and cAMP redistributed CFTR to the apical membrane. cAMP-dependent recruitment of CFTR to the apical membrane was accompanied by recruitment of AQP5 that was reversed by a PKA inhibitor. cAMP also induced apical trafficking of V-ATPase and redistribution of NKCC1 and NBCe1 to the basolateral membranes. The steady-state distribution of AQP5, CFTR, NBCe1, NKCC1, and V-ATPase in human Brunner's glands from healthy controls, cystic fibrosis, and celiac disease resembled that of rat; however, the distribution profiles were markedly attenuated in the disease-affected duodenum. These data support functional transport of chloride, bicarbonate, water, and protons by second messenger-regulated traffic in mammalian Brunner's glands under physiological and pathophysiological conditions.

[Long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma].

PubMed

Zhang, Xiangmin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Zeng, Guoxing; Lan, Xiaolin

2013-02-01

To evaluate the long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Sixty-five cases of nasopharyngeal carcinoma patients were randomly divided into study group of 32 patients and control group of 33 patents. The submandibular gland was transferred to submental region on 32 cases with nasopharyngeal carcinoma before receiving conventional radiotherapy and a block was used to cover the submental region. Before radiotherapy, two groups of submandibular gland function was detected by imaging of the submandibular gland. At 60 months after radiotherapy, submandibular gland function was detected by 99mTc radionuclide scanning, the questionnaire about the degree of xerostomia was investigated respectively. Five-year survival rate was counted. After following up for 60 months, submandibular gland uptake and secretion function in the study group was significantly higher than that in the control group, there was significant difference between the two groups (P < 0.01) respectively. The incidence of moderate or severe xerostomia in the study group was significantly lower than that in the control group (15.4% vs 76.9%, P < 0.01). Five-year survival rate of the study group and control group was 81.3% and 78.8% respectively, there was no significant difference between the two groups (P > 0.05). The long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma was well. It could improve the quality of life in nasopharyngeal carcinoma patients after radiotherapy, and did not affect the long-term efficacy of nasopharyngeal carcinoma.

Pituitary gland imaging and outcome.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Gallizia, Anna Lisa; Maghnie, Mohamad

2012-01-01

Magnetic resonance imaging (MRI) allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. The identification of posterior pituitary hyperintensity, now considered a marker of neurohypophyseal functional integrity, has been the most striking advance for the diagnosis and understanding of anterior and posterior pituitary diseases. The advent of MRI has in fact led to a significant improvement in the understanding of the pathogenesis of disorders that affect the hypothalamo-pituitary area. Today, there is convincing evidence to support the hypothesis that marked MRI differences in pituitary morphology indicate a diverse range of disorders which affect the organogenesis and function of the anterior pituitary gland with different prognoses. Furthermore, the association of extrapituitary malformations accurately defined by MRI has supported a better definition of several conditions linked to pituitary hormone deficiencies and midline defects. MRI is a very informative procedure that should be used to support a diagnosis of hypopituitarism. It is useful in clinical management, because it helps endocrinologists determine which patients to target for further molecular studies and genetic counselling, which ones to screen for additional hormone deficits, and which ones may need growth hormone replacement into adult life. Copyright © 2012 S. Karger AG, Basel.

Resistance exercise induces region-specific adaptations in anterior pituitary gland structure and function in rats.

PubMed

Kraemer, William J; Flanagan, Shawn D; Volek, Jeff S; Nindl, Bradley C; Vingren, Jakob L; Dunn-Lewis, Courtenay; Comstock, Brett A; Hooper, David R; Szivak, Tunde K; Looney, David P; Maresh, Carl M; Hymer, Wesley C

2013-12-01

The anterior pituitary gland (AP) increases growth hormone (GH) secretion in response to resistance exercise (RE), but the nature of AP adaptations to RE is unknown. To that end, we examined the effects of RE on regional AP somatotroph GH release, structure, and relative quantity. Thirty-six Sprague-Dawley rats were assigned to one of four groups: 1) no training or acute exercise (NT-NEX); 2) no training with acute exercise (NT-EX); 3) resistance training without acute exercise (RT-NEX); 4) resistance training with acute exercise (RT-EX). RE incorporated 10, 1 m-weighted ladder climbs at an 85° angle. RT groups trained 3 days/wk for 7 wk, progressively. After death, trunk blood was collected, and each AP was divided into quadrants (ventral-dorsal and left-right). We measured: 1) trunk plasma GH; 2) somatotroph GH release; 3) somatotroph size; 4) somatotroph secretory content; and 5) percent of AP cells identified as somatotrophs. Trunk GH differed by group (NT-NEX, 8.9 ± 2.4 μg/l; RT-NEX, 9.2 ± 3.5 μg/l; NT-EX, 15.6 ± 3.4 μg/l; RT-EX, 23.4 ± 4.6 μg/l). RT-EX demonstrated greater somatotroph GH release than all other groups, predominantly in ventral regions (P < 0.05-0.10). Ventral somatotrophs were larger in NT-EX and RT-NEX compared with RT-EX (P < 0.05-0.10). RT-NEX exhibited significantly greater secretory granule content than all other groups but in the ventral-right region only (P < 0.05-0.10). Our findings indicate reproducible patterns of spatially distinct, functionally different somatotroph subpopulations in the rat pituitary gland. RE training appears to induce dynamic adaptations in somatotroph structure and function.

[NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

PubMed

Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

2016-01-01

The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

Sensitivity of Salivary Glands to Radiation

PubMed Central

Grundmann, O.; Mitchell, G.C.; Limesand, K.H.

2009-01-01

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field. PMID:19783796

Physical Changes in Human Meibum with Age as Measured by Infrared Spectroscopy

PubMed Central

Borchman, Douglas; Foulks, Gary N.; Yappert, Marta C.; Kakar, Shelly; Podoll, Nathan; Rychwalski, Paul; Schwietz, Eric

2010-01-01

Both lipids and mucins contribute to the stability of the tear film and lipids may inhibit tears from evaporating. Younger people have lower lipid viscosity, higher lipid volume, and a lower rate of tear evaporation. Since age-related changes in human meibum composition and conformation have never been investigated, as a basis for the study of lipid-associated changes with meibomian gland dysfunction, we used the power of infrared spectroscopy to characterize hydrocarbon chain conformation and packing in meibum from humans without dry eye symptoms in relation to age and sex. Meibum from normal human donors ranging in age from 3 to 88 years was studied. Meibum phase transitions were quantified by fitting them to a 4-parameter 2-state sigmoidal equation. Human meibum order and phase transition temperatures decrease with age and this trend may be attributed to lipid compositional changes. If meibum has the same thermodynamic properties on the surface of the tears as it does on the lid margin, a decrease in lipid-lipid interaction strength with increasing age could decrease the stability of tears since lipid-lipid interactions on the tear surface must be broken for the tear film to break up. This study also serves as a foundation to examine meibum conformational differences in meibum from people with meibomian gland dysfunction. PMID:20160464

Effect of pulsed laser light in patients with dry eye syndrome.

PubMed

Guilloto Caballero, S; García Madrona, J L; Colmenero Reina, E

2017-11-01

The objective of this study was to determine the clinical benefits of pulsed light therapy for the treatment of Dry Eye Syndrome (DES) due to the decrease in aqueous tear production (aqueous deficient DES) and/or excessive tear evaporation (evaporative DES) due to Meibomian Gland Dysfunction (MGD). A study was conducted on 72 eyes corresponding to 36 patients with DES. Out of these 72 eyes, 60 underwent refractive surgery (48 with femtosecond laser, 6 were operated with a mechanical microkeratome, and 6 with refractive photo-keratectomy[RPK], 6 treated with phacoemulsification, and 6 with no previous surgical treatment. Pulsed laser light (Intense Pulsed Light Regulated [IRPL ® ]) was use to stimulate the secretion of the Meibomian glands during 4 sessions, one every 15 days. Patients with aqueous deficient DES did not show any improvement. Eyes with no previous surgery and those treated with phacoemulsification and PRK had a favourable outcome. On the other hand, less conclusive results were observed in the eyes treated with excimer laser. This treatment could be very helpful to treat evaporative DES produced by MGD. On the other hand, it is not helpful for those cases related to an isolated damage in the aqueous phase, or the mucin phase. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Participation of pineal gland in antistressor activity of adaptogenic drugs].

PubMed

Arushanian, É B; Beĭer, É V

2015-01-01

Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs.

Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer

PubMed Central

van Luijk, Peter; Pringle, Sarah; Deasy, Joseph O.; Moiseenko, Vitali V.; Faber, Hette; Hovan, Allan; Baanstra, Mirjam; van der Laan, Hans P.; Kierkels, Roel G. J.; van der Schaaf, Arjen; Witjes, Max J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Wu, Jonn; Coppes, Robert P.

2016-01-01

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia. PMID:26378247

Granular cutaneous glands in the frog Physalaemus biligonigerus (Anura, Leptodactylidae): comparison between ordinary serous and 'inguinal' glands.

PubMed

Delfino, G; Brizzi, R; Alvarez, B B; Gentili, M

1999-12-01

Beside the ordinary granular (or serous) glands, the skin of the leptodactylid frog Physalaemus biligonigerus possesses peculiar clusters of large granular units, the 'inguinal' glands, located in the dorsolateral areas of the pelvic girdle. Both gland types store their specific products within the syncytial cytoplasm of the secretory unit. These secretory materials consist of spheroidal or ellipsoidal bodies (granules) with a repeating substructure. The subcellular features of the immature products of the ordinary serous and inguinal glands are identical. However, these products undergo divergent maturative processes, leading to fluidation on the one hand and condensation on the other. Secretory release into the small gland lumen was observed in both cases, involving merocrine mechanisms. On the basis of the analysis of cutaneous serous gland polymorphism in anurans, the inguinal units in P. biligonigerus do not appear to be an independent line. Rather, these large units belong to the ordinary serous type and represent a gland population specialized in the storage of remarkable amounts of product used in chemical defence of the skin.

Intralobular ducts of human major salivary glands contain leptin and its receptor.

PubMed

De Matteis, R; Puxeddu, R; Riva, A; Cinti, S

2002-11-01

Leptin, a 16-kDa hormone, plays an important role in the control of food intake and in energy homeostasis both in rodents and in man. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. In addition, a leptin receptor has been detected in taste cells of mouse circumvallate papillae and in rat intestinal epithelium. These data prompted us to carry out a detailed study of human salivary glands as potential leptin-producing organs. Biopsies of salivary glands (submandibular and parotid) obtained from male and female patients during surgery for different clinical indications were subjected to immunohistochemical study for the presence of leptin, its functional receptor, insulin and glucagon. The presence and cellular distribution of glucocorticoid receptor in leptin-secreting cells were also investigated. Double immunohistochemical staining (silver-gold intensification and avidin-biotin-peroxidase) was used for the visualization of glucocorticoid receptor and leptin labelling, respectively. The results show that intralobular duct cells of submandibular and parotid glands are immunoreactive for leptin, leptin receptor and glucagon but not for insulin. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.

Effect of radioactive iodine therapy on lacrimal gland functions in patients with hyperthyroidism.

PubMed

Aydogan, Fusun; Ayhan Tuzcu, Esra; Aydogan, Akin; Akkucuk, Seckin; Coskun, Mesut; Ustun, Ihsan; Gökçe, Cumali

2014-04-01

Radioactive iodine (RAI) therapy is preferred in the treatment of hyperthyroidism because of its effectiveness, noninvasiveness, and low costs. I has been detected in extrathyroidal tissues, such as in gastric mucosa, salivary glands, and lacrimal glands. To the best of our knowledge, there is no publication concerning the effects of RAI therapy for hyperthyroidism on tear production. In the present study, we evaluated whether or not the lacrimal glands are affected after RAI therapy when compared with pretreatment period. The Schirmer and tear break-up time (TBUT) tests were used to assess 32 eyes of 16 patients with conditions that were diagnosed as hyperthyroidism before and at 3 and 6 months after RAI treatment. In addition, pretreatment values of patients were compared with that of controls. It was evaluated whether or not a correlation exists between the results and the dose or iodine uptake values. There was no significant difference between pretreatment values of Schirmer and TBUT tests obtained in the patient group and those of the control group (P > 0.05). In the patient group, there was a significant difference between the posttreatment and pretreatment values (P < 0.05). There was a positive correlation between uptake values obtained at 24 hours and the values obtained by TBUT and Schirmer tests on both eyes at 3 and 6 months. At 6 months, the uptake value at 24 hours was 28.83 ± 60 for both eyes in patients with TBUT test values less than 10, whereas it was 39.25 ± 7.88 for the right eye and 39.00 ± 6.85 for the left eyes in patients with TBUT test values greater than 10. The difference was statistically significant (P < 0.05). In our study, we concluded that the decrease in mucin and aqueous production occurs due to affected lacrimal glands by RAI therapy; however, this effect is not dose dependent.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway.

PubMed

Zhang, Rui; Ma, Huimin; Gao, Yuan; Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial; Liu, Xiaolong; Ge, Gaoxiang

2018-02-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

PubMed Central

Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial

2018-01-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation. PMID:29420538

Hunting with sticky tape: functional shift in silk glands of araneophagous ground spiders (Gnaphosidae).

PubMed

Wolff, Jonas O; Řezáč, Milan; Krejčí, Tomáš; Gorb, Stanislav N

2017-06-15

Foraging is one of the main evolutionary driving forces shaping the phenotype of organisms. In predators, a significant, though understudied, cost of foraging is the risk of being injured by struggling prey. Hunting spiders that feed on dangerous prey like ants or other spiders are an extreme example of dangerous feeding, risking their own life over a meal. Here, we describe an intriguing example of the use of attachment silk (piriform silk) for prey immobilization that comes with the costs of reduced silk anchorage function, increased piriform silk production and additional modifications of the extrusion structures (spigots) to prevent their clogging. We show that the piriform silk of gnaphosids is very stretchy and tough, which is an outstanding feat for a functional glue. This is gained by the combination of an elastic central fibre and a bi-layered glue coat consisting of aligned nanofibrils. This represents the first tensile test data on the ubiquitous piriform gland silk, adding an important puzzle piece to the mechanical catalogue of silken products in spiders. © 2017. Published by The Company of Biologists Ltd.

Substance P is a functional neurotransmitter in the rat parotid gland.

PubMed

Gallacher, D V

1983-09-01

subsequently abolished the non-cholinergic, non-adrenergic field stimulus-evoked enzyme release. The putative substance P antagonist, D-Pro2, D-Trp7,9 substance P, reversibly blocked the response to both non-cholinergic, non-adrenergic nerve stimulation and exogenous substance P. It was demonstrated however that prolonged exposure to this antagonist is associated with non-reversible and, importantly, non-specific neurotoxic effects. It is concluded that substance P or a closely related peptide is a functional neurotransmitter in the rat parotid gland.

Dufour's gland and poison gland chemistry of the myrmicine ant,Messor capensis (Mayr).

PubMed

Brand, J M; Mpuru, S P

1993-07-01

The Cape harvester ant,Messor capensis (Mayr), is widespread in the more arid regions of southern Africa, where it forms trails many meters long and harvests considerable quantities of seeds. The poison gland contains primarily the alkaloid, anabaseine, with minor amounts of the related alkaloid, anabasine, and an unidentified compound. The Dufour's gland contains predominantly alkanes and alkenes of carbon chain length 12-23.n-Pentadecane is the major component, with lesser amounts ofn-pentadecene,n-tridecane,n-heptadecane,n-tetradecane,n-heneicosene, andn-tricosene. The dienes,n-heneicosadiene andn-tricosadiene are rather unusual components of the Dufour's gland of ants.

Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer.

PubMed

Rodríguez-Fernández, Lucía; Ferrer-Vicens, Iván; García, Concha; Oltra, Sara S; Zaragozá, Rosa; Viña, Juan R; García-Trevijano, Elena R

2016-09-15

Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E-cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Calcium signalling in salivary gland physiology and dysfunction

PubMed Central

2015-01-01

Abstract Studies over the past four decades have established that Ca2+ is a critical factor in control of salivary gland function and have led to identification of the critical components of this process. The major ion transport mechanisms and ion channels that are involved in fluid secretion have also been established. The key event in activation of fluid secretion is an increase in [Ca2+]i triggered by inositol 1,4,5‐trisphosphate (IP3)‐induced release of Ca2+ from ER via the IP3 receptor (IP3R). IP3Rs determine the site of initiation and the pattern of the [Ca2+]i signal in the cell. However, Ca2+ entry into the cell is required to sustain the elevation of [Ca2+]i and fluid secretion and is mediated by the store‐operated Ca2+ entry (SOCE) mechanism. Orai1, TRPC1, TRPC3 and STIM1 have been identified as critical components of SOCE in these cells. Cells finely tune the generation and amplification of [Ca2+]i signals for regulation of cell function. An important emerging area is the concept that unregulated [Ca2+]i signals in cells can directly cause cell damage, dysfunction and disease. Alternatively, aberrant [Ca2+]i signals can also amplify and increase the rates of cell damage. Such defects in Ca2+ signalling have been described in salivary glands in conjunction with radiation‐induced loss of salivary gland function as well as in the salivary defects associated with the autoimmune exocrinopathy Sjögren's syndrome. Such defects have been associated with altered function or expression of key Ca2+ signalling components, such as STIM proteins and TRP channels. These studies offer new avenues for examining the mechanisms underlying the disease and development of novel clinical targets and therapeutic strategies. PMID:26592972

Clinical Management of Salivary Gland Hypofunction and Xerostomia in Head-and-Neck Cancer Patients: Successes and Barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vissink, Arjan; Mitchell, James B.; Baum, Bruce J.

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: successes and barriers*

PubMed Central

Vissink, Arjan; Mitchell, James B; Baum, Bruce J; Limesand, Kirsten H; Jensen, Siri Beier; Fox, Philip C; Elting, Linda S; Langendijk, Johannes A; Coppes, Robert P; Reyland, Mary E

2010-01-01

The most significant long-term complication of radiotherapy in the head and neck region is hyposalivation and its related complaints, particularily xerostomia. This paper addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to: (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. PMID:20970030

Unraveling dual feeding associated molecular complexity of salivary glands in the mosquito Anopheles culicifacies

PubMed Central

Sharma, Punita; Sharma, Swati; Mishra, Ashwani Kumar; Thomas, Tina; Das De, Tanwee; Rohilla, Suman Lata; Singh, Namita; Pandey, Kailash C.; Valecha, Neena; Dixit, Rajnikant

2015-01-01

ABSTRACT Mosquito salivary glands are well known to facilitate meal acquisition, however the fundamental question on how adult female salivary gland manages molecular responses during sugar versus blood meal uptake remains unanswered. To investigate these responses, we analyzed a total of 58.5 million raw reads generated from two independent RNAseq libraries of the salivary glands collected from 3–4 day-old sugar and blood fed Anopheles culicifacies mosquitoes. Comprehensive functional annotation analysis of 10,931 contigs unraveled that salivary glands may encode diverse nature of proteins in response to distinct physiological feeding status. Digital gene expression analysis and PCR validation indicated that first blood meal significantly alters the molecular architecture of the salivary glands. Comparative microscopic analysis also revealed that first blood meal uptake not only causes an alteration of at least 12–22% of morphological features of the salivary glands but also results in cellular changes e.g. apoptosis, confirming together that adult female salivary glands are specialized organs to manage meal specific responses. Unraveling the underlying mechanism of mosquito salivary gene expression, controlling dual feeding associated responses may provide a new opportunity to control vector borne diseases. PMID:26163527

Filling dynamics of the Brindley's glands in the blood-sucking bug Triatoma infestans (Hemiptera: Reduviidae).

PubMed

Palottini, Florencia; González, Andrés; Manrique, Gabriel

2014-12-01

The filling dynamics of exocrine defensive glands is an important component of the defensive capacity of an insect in its natural environment. We studied the filling state and reloading rate of the Brindley's glands in the haematophagous Chagas disease vector Triatoma infestans (Hemiptera: Reduviidae). Quantitative analyses of isobutyric acid, the main secretion component, were carried out with glands dissected from adults under different scenarios of development, number of discharging events and feeding conditions. The alarm-pheromone function of the gland secretion was also assessed in bioassays with conspecific nymphs. Although pharate adults have their glands completely developed, these were not full until imaginal ecdysis. If kept undisturbed, the adults maintained a constant gland load, and discharged about 75% of the gland contents upon one disturbance event. While the glands can be discharged several times, full replenishing was not complete after one week, unless the insect had access to food. The escape behavior of nymphs in bioassays correlated with the chemical analyses, with nymphs showing significant avoidance only toward gland discharges from undisturbed or disturbed/fed adults. The results are discussed in reference to the feeding frequency and gregarious behavior of T. infestans under natural conditions, which suggest a relevant role of the filling dynamics of the Brindley's glands in the intraspecific communication of the insect. Copyright © 2014 Elsevier Ltd. All rights reserved.

A critical analysis of carbonic anhydrase function, respiratory gas exchange, and the acid-base control of secretion in the rectal gland of Squalus acanthias.

PubMed

Shuttleworth, Trevor J; Thompson, Jill; Munger, R Stephen; Wood, Chris M

2006-12-01

elevated perfusate HCO(3)(-) concentrations. We conclude that pH effects on rectal gland secretion rate are adaptive, that CA functions to catalyze the hydration of CO(2), thereby maintaining a gradient for diffusive efflux of CO(2) from the working cells, and that differences in response to CA inhibition likely reflect the higher perfusion-to-secretion ratio in vitro than in vivo.

Selective expression of neuropeptides in the rat mammary gland: somatostatin gene is expressed during lactation.

PubMed

Chen, A; Laskar-Levy, O; Koch, Y

1999-12-01

, examined by RT-PCR, are not expressed by the mammary gland suggest that these neuropeptides are actively concentrated by the mammary glands from the general circulation. The GnRH gene has been previously demonstrated to be expressed in the mammary gland, and in this study somatostatin was the only neuropeptide that was found to be produced by the mammary gland. The observation that only a small portion of the neuropeptides that are present in milk are being produced by the lactating mammary gland suggest that these neuropeptides have important functions in the biology of the suckling neonate and probably also in the development and function of the breast.

A median third eye: pineal gland retraces evolution of vertebrate photoreceptive organs.

PubMed

Mano, Hiroaki; Fukada, Yoshitaka

2007-01-01

In many vertebrates, the pineal gland serves as a photoreceptive neuroendocrine organ. Morphological and functional similarities between the pineal and retinal photoreceptor cells indicate their close evolutionary relationship, and hence the comparative studies on the pineal gland and the retina are the keys to deciphering the evolutionary traces of the vertebrate photoreceptive organs. Several studies have suggested common genetic and molecular mechanisms responsible for their similarities, but largely unknown are those underlying pineal-specific development and physiological functions. Recent studies have identified several cis-acting DNA elements that participate in transcriptional control of the pineal-specific genes. Genetic approaches in the zebrafish have also contributed to elucidating the genetic network regulating the pineal development and neurogenesis. These efforts toward elucidating the molecular instrumentation intrinsic to the pineal gland, back to back with those to the retina, should lead to a comprehensive understanding of the evolutionary history of the vertebrate photoreceptive structures. This article summarizes the current status of research on these topics.

Characterization of the myoepithelial cells in the major salivary glands of the fruit bat Artibeus jamaicensis.

PubMed

Guerrero-Hernández, Julio; Moreno-Mendoza, Norma

2016-08-01

Bats constitute one of the most numerous mammalian species. Bats have a wide range of dietary habits and include carnivorous, haematophagous, insectivorous, frugivorous and nectivorous species. The salivary glands of these species have been of particular research interest due to their structural variability among chiropterans with different types of diets. Myoepithelial cells (MECs), which support and facilitate the expulsion of saliva from the secretory portions of salivary glands, are very important for their function; however, this cell type has not been extensively studied in the salivary glands of bats. In this study, we characterized the MECs in the major salivary glands of the fruit bat Artibeus jamaicensis. Herein, we describe the morphology of the parotid, submandibular and sublingual glands of A. jamaicensis at the light- and electro-microscopic level and the distribution of MECs in these glands, as defined by their expression of smooth-muscle markers such as α-smooth muscle actin (SMAα) and desmin, and of epithelial cell markers, such as KRT14. We found that the anatomical locations of the major salivary glands in this bat species are similar to those of humans, except that the bat sublingual gland appears to be unique, extending to join the contralateral homologous gland. Morphologically, the parotid gland has the characteristics of a mixed-secretory gland, whereas the submandibular and sublingual glands were identified as mucous-secretory glands. MECs positive for SMAα, KRT14 and desmin were found in all of the structural components of the three glands, except in their excretory ducts. Desmin is expressed at a lower level in the parotid gland than in the other glands. Our results suggest that the major salivary glands of A. jamaicensis, although anatomically and structurally similar to those of humans, play different physiological roles that can be attributed to the dietary habits of this species. © 2016 Anatomical Society.

Osmoregulation and salt gland Na, K-ATPase activity following exposure to the anticholinesterase fenthion

USGS Publications Warehouse

Rattner, B.A.; Fleming, W.J.; Murray, H.C.

1982-01-01

Salt gland function and osmoregulation in aquatic birds drinking hyperosmotic water has been suggested to be impaired by organophosphorus insecticides. To test this hypothesis, adult ducks (Anas rubripes) were provided various regimens of fresh or salt (1.5% NaCl) water (FW, SW) and mash containing vehicle or 21 ppm fenthion (Fn) on days 1-7 and 7-12 of this study. The 8 treatments (day 1-7:day 7-12) included :FW:FW, FW:FW+Fn, FW:SW, FW+Fn:SW, FW:SW+Fn, FW+Fn:SW+FN, SW;SW, and SW:5W+Fn. Ducks were bled by jugular venipuncture on days 1,7 and 12, and then sacrificed. Brain and salt gland acetylcholinesterase activities were substantially inhibited (44-52% and 14-26%) by Fn. However, plasma Na, Cl and osmolality, as indirect but cumulative indices of salt gland function, were uniformly elevated in all SW groups including those receiving Fn. In a second experiment, salt gland Na,K-ATPase activity was reduced after in vitro incubation with DDE (40 and 400 ?M; positive control), but was unaffected by Fn and its oxygen analog (0.04-400 ?M). The present findings suggest that environmentally realistic concentrations of organophosphorus insecticides do not affect osmoregulatory function in adult ducks.

[Chronic blepharoconjunctivitis during a treatment with acitretin (Soriatane)].

PubMed

Denis, P; Nordmann, J P; Saiag, P; Liotet, S; Laroche, L; Saraux, H

1993-01-01

We report external ocular side effects after treatment with acitretin, a new synthetic vitamin A analogue and the main metabolite of etretinate. A patient treated with 20-25 mg/day of acitretin for psoriasis suffered from chronic blepharoconjunctivitis. Schirmer tests, tear lysozyme were normal while rose bengal and fluorescein staining disclosed epithelial punctate defects and tear break-up time was shortened. Meibomian glands of the lower lid were photographed with transillumination and appeared atrophic. Conjunctival cytology and biopsy showed snake-like chromatine appearance, keratinized epithelial cells and some lymphocytes infiltrates. Accessory salivary gland histological aspects were nonspecific. There was a clear relationship between restarting the acitretin therapy and recurrence of ocular symptoms. Acitretin, like other retinoids, may induce or exacerbate blepharoconjunctivitis in patients with psoriasis.

Precise measurement of volume of eccrine sweat gland in mental sweating by optical coherence tomography

NASA Astrophysics Data System (ADS)

Sugawa, Yoshihiko; Fukuda, Akihiro; Ohmi, Masato

2015-04-01

We have demonstrated dynamic analysis of the physiological function of eccrine sweat glands underneath skin surface by optical coherence tomography (OCT). In this paper, we propose a method for extraction of the specific eccrine sweat gland by means of the connected component extraction process and the adaptive threshold method, where the en face OCT images are constructed by the swept-source OCT. In the experiment, we demonstrate precise measurement of the volume of the sweat gland in response to the external stimulus.

Gland segmentation in prostate histopathological images

PubMed Central

Singh, Malay; Kalaw, Emarene Mationg; Giron, Danilo Medina; Chong, Kian-Tai; Tan, Chew Lim; Lee, Hwee Kuan

2017-01-01

Abstract. Glandular structural features are important for the tumor pathologist in the assessment of cancer malignancy of prostate tissue slides. The varying shapes and sizes of glands combined with the tedious manual observation task can result in inaccurate assessment. There are also discrepancies and low-level agreement among pathologists, especially in cases of Gleason pattern 3 and pattern 4 prostate adenocarcinoma. An automated gland segmentation system can highlight various glandular shapes and structures for further analysis by the pathologist. These objective highlighted patterns can help reduce the assessment variability. We propose an automated gland segmentation system. Forty-three hematoxylin and eosin-stained images were acquired from prostate cancer tissue slides and were manually annotated for gland, lumen, periacinar retraction clefting, and stroma regions. Our automated gland segmentation system was trained using these manual annotations. It identifies these regions using a combination of pixel and object-level classifiers by incorporating local and spatial information for consolidating pixel-level classification results into object-level segmentation. Experimental results show that our method outperforms various texture and gland structure-based gland segmentation algorithms in the literature. Our method has good performance and can be a promising tool to help decrease interobserver variability among pathologists. PMID:28653016

MO-F-CAMPUS-I-01: EIT Imaging to Monitor Human Salivary Gland Functionality: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohli, K; Karvat, A; Liu, J

Purpose: Clinically, there exists a need to develop a non-invasive technique for monitoring salivary activity. In this study, we investigate the feasibility of a using the electrical conductivity information from Electrical Impedance Tomography (EIT) to monitor salivary flow activity. Methods: To acquire EIT data, eight Ag/AgCl ECG electrodes were placed around the mandible of the subject. An EIT scan was obtained by injecting current at 50 KHz, 0.4 mA through each pair of electrodes and recording voltage across other electrode pairs. The functional conductivity image was obtained through reconstruction of the voltage data, using Electrical Impedance Tomography and Diffuse Opticalmore » Tomography Reconstruction Software (EIDORS) in Matlab. In using EIDORS, forward solution was obtained using a user-defined finite element model shape and inverse solution was obtained using one-step Gaussian solver. EIT scans of volunteer research team members were acquired for three different physiological states: pre-stimulation, stimulation and post-stimulation. For pre-stimulation phase, data were collected in intervals of 5 minutes for 15 minutes. The salivary glands were then stimulated in the subject using lemon and the data were collected immediately. Post-stimulation data were collected at 4 different timings after stimulation. Results: Variations were observed in the electrical conductivity patterns near parotid regions between the pre- and post-stimulation stages. The three images acquired during the 15 minute pre-stimulation phase showed no major changes in the conductivity. Immediately after stimulation, electrical conductivity increased near parotid regions and 15 minutes later slowly returned to pre-stimulation level. Conclusion: In the present study involving human subjects, the change in electrical conductivity pattern shown in the EIT images, acquired at different times with and without stimulation of salivary glands, appeared to be consistent with the change in

A new type of exocrine gland and its function in mass recruitment in the ant Cylindromyrmex whymperi (Formicidae, Cerapachyinae)

NASA Astrophysics Data System (ADS)

Gobin, Bruno; Rüppell, Olav; Hartmann, Annegret; Jungnickel, Harald; Morgan, David; Billen, Johan

2001-08-01

Workers of the ant Cylindromyrmex whymperi display mass trail recruitment. Bioassays show that the trail pheromone originates from a unique gland between abdominal sternites 6 and 7. The gland has a hitherto unknown structural organization. Upon leaving the secretory cell, the duct cell widens to form a sclerotized pear-shaped reservoir chamber, lined with multiple duct cells. Each duct thus forms a miniature reservoir for the secretions of each single secretory cell, a novel structural arrangement in exocrine glands of social Hymenoptera.

The mystery of the thymus gland.

PubMed

Liu, Daniel; Ellis, Harold

2016-09-01

The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über "Endocarditis puerperalis," vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679-684, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Postpharyngeal Gland: Specialized Organ for Lipid Nutrition in Leaf-Cutting Ants

PubMed Central

Decio, Pâmela; Vieira, Alexsandro Santana; Dias, Nathalia Baptista; Palma, Mario Sergio; Bueno, Odair Correa

2016-01-01

There are several hypotheses about the possible functions of the postpharyngeal gland (PPG) in ants. The proposed functions include roles as cephalic or gastric caeca and diverticulum of the digestive tract, mixing of hydrocarbons, nestmate recognition, feeding larvae, and the accumulation of lipids inside this gland, whose origin is contradictory. The current study aimed to investigate the functions of these glands by examining the protein expression profile of the PPGs of Atta sexdens rubropilosa (Hymenoptera, Formicidae). Mated females received lipid supplementation and their glands were extracted and analyzed using a proteomic approach. The protocol used combined two-dimensional electrophoresis and shotgun strategies, followed by mass spectrometry. We also detected lipid β-oxidation by immunofluorescent marking of acyl-CoA dehydrogenase. Supplying ants with lipids elicited responses in the glandular cells of the PPG; these included increased expression of proteins related to defense mechanisms and signal transduction and reorganization of the cytoskeleton due to cell expansion. In addition, some proteins in PPG were overexpressed, especially those involved in lipid and energy metabolism. Part of the lipids may be reduced, used for the synthesis of fatty alcohol, transported to the hemolymph, or may be used as substrate for the synthesis of acetyl-CoA, which is oxidized to form molecules that drive oxidative phosphorylation and produce energy for cellular metabolic processes. These findings suggest that this organ is specialized for lipid nutrition of adult leaf-cutting ants and characterized like a of diverticulum foregut, with the ability to absorb, store, metabolize, and mobilize lipids to the hemolymph. However, we do not rule out that the PPG may have other functions in other species of ants. PMID:27149618

The Postpharyngeal Gland: Specialized Organ for Lipid Nutrition in Leaf-Cutting Ants.

PubMed

Decio, Pâmela; Vieira, Alexsandro Santana; Dias, Nathalia Baptista; Palma, Mario Sergio; Bueno, Odair Correa

2016-01-01

There are several hypotheses about the possible functions of the postpharyngeal gland (PPG) in ants. The proposed functions include roles as cephalic or gastric caeca and diverticulum of the digestive tract, mixing of hydrocarbons, nestmate recognition, feeding larvae, and the accumulation of lipids inside this gland, whose origin is contradictory. The current study aimed to investigate the functions of these glands by examining the protein expression profile of the PPGs of Atta sexdens rubropilosa (Hymenoptera, Formicidae). Mated females received lipid supplementation and their glands were extracted and analyzed using a proteomic approach. The protocol used combined two-dimensional electrophoresis and shotgun strategies, followed by mass spectrometry. We also detected lipid β-oxidation by immunofluorescent marking of acyl-CoA dehydrogenase. Supplying ants with lipids elicited responses in the glandular cells of the PPG; these included increased expression of proteins related to defense mechanisms and signal transduction and reorganization of the cytoskeleton due to cell expansion. In addition, some proteins in PPG were overexpressed, especially those involved in lipid and energy metabolism. Part of the lipids may be reduced, used for the synthesis of fatty alcohol, transported to the hemolymph, or may be used as substrate for the synthesis of acetyl-CoA, which is oxidized to form molecules that drive oxidative phosphorylation and produce energy for cellular metabolic processes. These findings suggest that this organ is specialized for lipid nutrition of adult leaf-cutting ants and characterized like a of diverticulum foregut, with the ability to absorb, store, metabolize, and mobilize lipids to the hemolymph. However, we do not rule out that the PPG may have other functions in other species of ants.

Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum

PubMed Central

Choi, Eunyoung; Roland, Joseph T.; Barlow, Brittney J.; O’Neal, Ryan; Rich, Amy E.; Nam, Ki Taek; Shi, Chanjuan; Goldenring, James R.

2014-01-01

Objective The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. Design We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. Results The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of stomach as well as in over 50% of antral glands. MIST1-expressing chief cells were predominantly observed in the body, although individual glands of the antrum also showed MIST1-expressing chief cells. While classically-described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed-type glands containing both parietal cells and G cells throughout the antrum. Conclusions Enteroendocrine cells show distinct patterns of localization in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. PMID:24488499

Is the Salivary Gland Associated with Honey Bee Recognition Compounds in Worker Honey Bees (Apis mellifera)?

PubMed

Martin, Stephen J; Correia-Oliveira, Maria E; Shemilt, Sue; Drijfhout, Falko P

2018-06-07

Cuticular hydrocarbons (CHCs) function as recognition compounds with the best evidence coming from social insects such as ants and honey bees. The major exocrine gland involved in hydrocarbon storage in ants is the post-pharyngeal gland (PPG) in the head. It is still not clearly understood where CHCs are stored in the honey bee. The aim of this study was to investigate the hydrocarbons and esters found in five major worker honey bee (Apis mellifera) exocrine glands, at three different developmental stages (newly emerged, nurse, and forager) using a high temperature GC analysis. We found the hypopharyngeal gland contained no hydrocarbons nor esters, and the thoracic salivary and mandibular glands only contained trace amounts of n-alkanes. However, the cephalic salivary gland (CSG) contained the greatest number and highest quantity of hydrocarbons relative to the five other glands with many of the hydrocarbons also found in the Dufour's gland, but at much lower levels. We discovered a series of oleic acid wax esters that lay beyond the detection of standard GC columns. As a bee's activities changed, as it ages, the types of compounds detected in the CSG also changed. For example, newly emerged bees have predominately C 19 -C 23 n-alkanes, alkenes and methyl-branched compounds, whereas the nurses' CSG had predominately C 31:1 and C 33:1 alkene isomers, which are replaced by a series of oleic acid wax esters in foragers. These changes in the CSG were mirrored by corresponding changes in the adults' CHCs profile. This indicates that the CSG may have a parallel function to the PPG found in ants acting as a major storage gland of CHCs. As the CSG duct opens into the buccal cavity the hydrocarbons can be worked into the comb wax and could help explain the role of comb wax in nestmate recognition experiments.

Rhythmic control of endocannabinoids in the rat pineal gland.

PubMed

Koch, Marco; Ferreirós, Nerea; Geisslinger, Gerd; Dehghani, Faramarz; Korf, Horst-Werner

2015-01-01

Endocannabinoids modulate neuroendocrine networks by directly targeting cannabinoid receptors. The time-hormone melatonin synchronizes these networks with external light condition and guarantees time-sensitive and ecologically well-adapted behaviors. Here, the endocannabinoid arachidonoyl ethanolamide (AEA) showed rhythmic changes in rat pineal glands with higher levels during the light-period and reduced amounts at the onset of darkness. Norepinephrine, the essential stimulus for nocturnal melatonin biosynthesis, acutely down-regulated AEA and other endocannabinoids in cultured pineal glands. These temporal dynamics suggest that AEA exerts time-dependent autocrine and/or paracrine functions within the pineal. Moreover, endocananbinoids may be released from the pineal into the CSF or blood stream.

Human lacrimal gland mucins.

PubMed

Paulsen, Friedrich; Langer, Gesa; Hoffmann, Werner; Berry, Monica

2004-05-01

The objective of this study was to determine whether the lacrimal gland synthesizes mucins and whether they are changed with age or in cases of dry eye. Expression of mucins in human lacrimal glands was monitored by reverse transcription-polymerase chain reaction analysis. Furthermore, the presence and distribution of MUC1, -2, -4, -5AC, -5B, -6 and -7 in epithelia of the human lacrimal gland and its excretory duct system were assessed with antisera to mucin peptide cores. Thirty normal tissues from cadavers of different ages were tested, plus four with dry eye treated with artificial tears. Expression studies detected mRNAs for mucins MUC1, -4, -5AC, -5B, -6 and -7; whereas the MUC2 message was absent. The message for MUC4 was present in all four cases of dry eye, but only in six out of the 30 normal glands from individuals who did not receive artificial tears. MUC6 mRNA was detected only in about half of the investigated samples. Immunohistochemistry revealed membrane-bound MUC1 at the apical surface of acinar cells, absence of MUC2, MUC5AC associated with goblet cells of excretory ducts, MUC5B and -7 in the cytoplasm of acinar cells, and MUC7 also in epithelial cells of excretory ducts. MUC4 mucin was detected only in those individuals in which message was identified. In dry eyes, MUC5AC and -5B were localized in the same acinar cells; whereas MUC2 and MUC6 were not detectable. Dot-blot analysis clearly revealed increased amounts of MUC4, -5AC, and -5B in the glands of elderly women who received treatment for dry eyes. These results confirm that the human lacrimal gland synthesizes a spectrum of mucins; part of them might be correlated with age. Copyright 2004 Springer-Verlag

Effect of subchronic zinc toxicity on rat salivary glands and serum composition.

PubMed

Mizari, Nazer; Hirbod-Mobarakeh, Armin; Shahinpour, Shervin; Ghalichi-Tabriz, Mostafa; Beigy, Maani; Yamini, Ali; Dehpour, Ahmad Reza

2012-11-01

Zinc plays an important role in a wide variety of metabolic processes in animal systems. The role of zinc in preservative treatment, fungicidal action and medicine, and addition of supplementary zinc have increased the probability of zinc toxicity, specially the chronic type. It is known that the composition and quantity of saliva influence the oral health. Regarding people's exposure to zinc in routine life and the importance of saliva, our purpose was to investigate the effects of oral zinc intoxication on secretory function in rat salivary glands and also on serum composition. In this study, there were five groups of female rats. Four groups received zinc acetate dehydrate through their drinking water. After 3 months of experiment, the chemical characteristics and flow rate of saliva and weight of salivary glands were determined. The effects of zinc on hematological and chemical factors of plasma were assessed too. Flow rate of submandibular glands was significantly lower in experimental groups and there were significant changes in Na(+), Ca(2+) and K(+) concentration both in saliva and in plasma. The serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, glucose levels in the plasma and urine creatinine levels were also altered in experimental groups in comparison with the control group. Our results show that zinc toxicity will affect the quantity and quality of saliva probably through changes in the various neurologic pathways to the salivary glands or effects on acinar cells of the salivary glands. Furthermore, our results showed that zinc toxicity will affect the liver and renal function.

Dry Eye Symptoms, Patient-Reported Visual Functioning, and Health Anxiety Influencing Patient Satisfaction After Cataract Surgery.

PubMed

Szakáts, Ildikó; Sebestyén, Margit; Tóth, Éva; Purebl, György

2017-06-01

To evaluate how patient satisfaction after cataract surgery is associated with postoperative visual acuity, visual functioning, dry eye signs and symptoms, health anxiety, and depressive symptoms. Fifty-four patients (mean age: 68.02 years) were assessed 2 months after uneventful phacoemulsification; 27 were unsatisfied with their postoperative results and 27 were satisfied. They completed the following questionnaires: Visual Function Index-14 (VF-14), Ocular Surface Disease Index (OSDI), Shortened Health Anxiety Inventory (SHAI), and Shortened Beck Depression Inventory. Testing included logarithm of the Minimum Angle of Resolution (logMAR) uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), dry eye tests (tear meniscus height and depth measured by spectral optical coherence tomography, tear film break-up time (TBUT), ocular surface staining, Schirmer 1 test, and meibomian gland dysfunction grading). Postoperative UCVA, BCVA, and the dry eye parameters - except TBUT - showed no statistically significant difference between the two groups (p > 0.130). However, the VF-14 scores, the OSDI scores, and the SHAI scores were significantly worse in the unsatisfied patient group (p < 0.002). No significant correlations were found between visual acuity measures and visual functioning (r < 0.170, p > 0.05). However, the VF-14 scores correlated with the OSDI scores (r = -0.436, p < 0.01) and the OSDI scores correlated with the SHAI scores (r = 0.333, p < 0.05). Multiple logistic regression revealed an adjusted association between patient satisfaction and dry eye symptoms (odds ratio = 1.46, 95% CI = 1.02-2.09, p = 0.038) and visual functioning (odds ratio = 0.78, 95% CI = 0.60-1.0, p = 0.048). Our results suggest that patient-reported visual functioning, dry eye symptoms, and health anxiety are more closely associated with patients' postoperative satisfaction than with the objective clinical measures of visual acuity or the signs of dry eye.

THE RESULTS OF USING RADIOIODINE FOR STUDIES OF THE FUNCTIONAL STATE OF THE THYROID GLAND IN CARDIOVASCULAR AND ALIMENTARY DISEASES (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalyuzhnii, I.T.

1962-04-01

The thyroid function in 60 healthy persons and 2000 patients was assessed. An elevated capacity of the thyroid gland to concentrate radioiodine was observed in almost 50% of rheumocarditis patients, one-third of lamblious cholecystitis cases, one-fourth of patients with rheumatic disease of the heart and circulatory insufficiency of the 1st and 2nd degrees, and more rarely in patients with neurosis, peptic ulcer, and hypertensive vascular disease of the 1st stage. Moderately low indexes of radioiodine accumulation in the thyroid gland were found in patients with subacute septic endocarditis, in two-thirds of patients with atherosclerosis and hypertensive vascular disease (2nd andmore » 3rd stages), in half of cases with rheumatic heart disease and circulatory insufficiency of the 3rd degree, as well as in pulmonary heart, chronic gastritis, and ulcerous disease. (auth)« less

Epidemiology of salivary gland infections.

PubMed

Cascarini, Luke; McGurk, Mark

2009-08-01

This article approaches sialadenitis from a personal perspective based on 15 years of clinical practice limited mainly to salivary gland diseases. Disorders of the salivary glands are uncommon. When they occur, experience in managing the process is diluted over a range of disciplines. The result is that traditional views go unchallenged and are recast unchanged from one textbook to another. Sialadenitis of bacterial origin is a relatively uncommon occurrence today and is normally associated with sialoliths. The most common viral infection of the salivary glands is mumps.

Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.

PubMed Central

Matsumoto, I; Tsubota, K; Satake, Y; Kita, Y; Matsumura, R; Murata, H; Namekawa, T; Nishioka, K; Iwamoto, I; Saitoh, Y; Sumida, T

1996-01-01

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS. PMID:8621782

Mycobacterium tuberculosis infection within parotid gland Warthin tumor.

PubMed

Ozcan, Cengiz; Apa, Duygu Düşmez; Aslan, Gönül; Gülhan, Stk; Görür, Kemal

2008-11-01

Tuberculosis of the parotid gland is extremely unusual. Tuberculosis comprises 2.5% to 10% of parotid gland lesions. Two clinical forms of parotid gland tuberculosis infection exist. One is a diffuse parenchymatous disease (either primary or secondary to nodal disease), resembling common infection. The second is a chronic, slow-growing, painless, and firm parotid mass mimicking a neoplasm. Most of these patients were diagnosed after parotid gland surgery and histopathologic evaluation. Warthin tumor is a well-known benign neoplasm of the salivary glands. It is the second most common tumor of the parotid gland. Mycobacterium tuberculosis within Warthin tumor is also unusual. Five cases with parotid gland tuberculosis within Warthin tumor were reported in the literature. In this report, we present a new patient with parotid gland tuberculosis within the Warthin tumor. This type parotid gland pathology is an extremely rare entity, and to the best of our knowledge, this is the second documented case using polymerase chain reaction. We also discussed the possible mechanisms of development of infection within Warthin tumor.

De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

PubMed

Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2014-06-01

In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

Transcriptome-Wide Identification of Preferentially Expressed Genes in the Hypothalamus and Pituitary Gland

PubMed Central

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2012-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12–15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland. PMID:22649398

Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

PubMed

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2011-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

Comparison of three methods for the estimation of pineal gland volume using magnetic resonance imaging.

PubMed

Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Ozçelik, Ozlem; Yıldırım, Birdal; Turgut, Mehmet

2012-01-01

Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm(3), respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation.

Comparison of Three Methods for the Estimation of Pineal Gland Volume Using Magnetic Resonance Imaging

PubMed Central

Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Özçelik, Özlem; Yıldırım, Birdal; Turgut, Mehmet

2012-01-01

Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm3, respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation. PMID:22619577

Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface.

PubMed

Schmidt, Tannin A; Sullivan, David A; Knop, Erich; Richards, Stephen M; Knop, Nadja; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Morrison, Sheila; Kam, Wendy R; Sullivan, Benjamin D

2013-06-01

Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4 ]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage.

TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunavala-Dossabhoy, Gulshan, E-mail: gsunav@lsuhsc.edu; Palaniyandi, Senthilnathan; Richardson, Charles

2012-09-01

Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect againstmore » IR-induced salivary hypofunction. Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation. Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D{sub 0} = 4.13 {+-} 1.0 Gy; {alpha}/{beta} = 0 Gy) compared with cells transduced with the TAT peptide (D{sub 0} = 4.91 {+-} 1.0 Gy; {alpha}/{beta} = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01). Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer.« less

Endocrine glands

MedlinePlus

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Precise measurement of instantaneous volume of eccrine sweat gland in mental sweating by optical coherence tomography

NASA Astrophysics Data System (ADS)

Sugawa, Yoshihiko; Fukuda, Akihiro; Ohmi, Masato

2015-03-01

We have demonstrated dynamic analysis of the physiological function of eccrine sweat glands underneath skin surface by optical coherence tomography (OCT). We propose a method for extraction of the target eccrine sweat gland by use of the connected component extraction process and the adaptive threshold method, where the en-face OCT images are constructed by the SS-OCT. Furthermore, we demonstrate precise measurement of instantaneous volume of the sweat gland in response to the external stimulus. The dynamic change of instantaneous volume of eccrine sweat gland in mental sweating is performed by this method during the period of 300 sec with the frame intervals of 3.23 sec.

Salivary gland diseases: infections, sialolithiasis and mucoceles.

PubMed

Delli, Konstantina; Spijkervet, Fred K L; Vissink, Arjan

2014-01-01

The three most frequently diagnosed salivary gland diseases are salivary gland infections, sialolithiasis and mucoceles. Salivary gland infections are usually of bacterial or viral etiology and can be divided into acute and chronic types. Occasionally they can result from obstruction of the salivary duct, an autoimmmune disease or cancer therapy. Infections can occur in all types of salivary glands and are observed at all ages. Sialolithiasis is characterized by the development of calcified structures in the salivary glands, especially in the submandibular gland. Sialoliths are generally attributed to retention of saliva and are usually accompanied by swelling and pain when a salivary stimulus is applied. Mucoceles can be differentiated into mucus extravasation phenomenon or mucus escape reaction, mucus retention cysts and ranulas. They result from extravasation of saliva into the surrounding soft tissues or from retention of saliva within the duct.

Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism

PubMed Central

Westmuckett, Andrew D.; Siefert, Joseph C.; Tesiram, Yasvir A.; Pinson, David M.; Moore, Kevin L.

2013-01-01

Background Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. Methodology/Principal Findings Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were ≈ 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine–induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. Conclusions/Significance Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism. PMID:23951251

Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum.

PubMed

Choi, Eunyoung; Roland, Joseph T; Barlow, Brittney J; O'Neal, Ryan; Rich, Amy E; Nam, Ki Taek; Shi, Chanjuan; Goldenring, James R

2014-11-01

The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of the stomach as well as in over 50% of antral glands. MIST1 expressing chief cells were predominantly observed in the body although individual glands of the antrum also showed MIST1 expressing chief cells. While classically described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed type glands containing both parietal cells and G cells throughout the antrum. Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The defensive secretion of Carabus lefebvrei Dejean 1826 pupa (Coleoptera, Carabidae): gland ultrastructure and chemical identification.

PubMed

Giglio, Anita; Brandmayr, Pietro; Dalpozzo, Renato; Sindona, Giovanni; Tagarelli, Antonio; Talarico, Federica; Brandmayr, Tullia Zetto; Ferrero, Enrico A

2009-05-01

This study documents the defensive function of flavored humor secreted by the abdominal glands of Carabus lefebvrei pupae. The morphology and the ultrastructure of these glands were described and the volatile compounds of glands secretion were identified by gas chromatography/mass spectrometry. The ultrastructure analysis shows an acinose complex formed by about 50 clusters. Each cluster has 20 glandular units and the unit-composed of one secretory and one canal cell lying along a duct-belongs to the class 3 cell type of Quennedey (1998). In the cytoplasm, the secretory cell contains abundant rough endoplasmatic reticula, glycogen granules, numerous mitochondria, and many well-developed Golgi complexes producing electron-dense secretory granules. Mitochondria are large, elongated, and often adjoining electronlucent vesicles. The kind and the origin of secretory granules varying in size and density were discussed. The chemical analysis of the gland secretion revealed the presence of a mixture of low molecular weight terpenes, ketones, aldehydes, alcohols, esters, and carboxylic acids. Monoterpenes, especially linalool, were the major products. We supposed that ketones, aldehydes, alcohols, esters, and carboxylic acids have a deterrent function against the predators and monoterpenes provide a prophylaxis function against pathogens. (c) 2008 Wiley-Liss, Inc.

Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

PubMed

Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

2016-10-01

Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional.

The pituitary gland: a brief history.

PubMed

Kaplan, Solomon Alexander

2007-01-01

The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus.

Three-dimensional cell shapes and arrangements in human sweat glands as revealed by whole-mount immunostaining

PubMed Central

Kurata, Ryuichiro; Futaki, Sugiko; Nakano, Itsuko; Fujita, Fumitaka; Tanemura, Atsushi; Murota, Hiroyuki; Katayama, Ichiro; Okada, Fumihiro

2017-01-01

Because sweat secretion is facilitated by mechanical contraction of sweat gland structures, understanding their structure-function relationship could lead to more effective treatments for patients with sweat gland disorders such as heat stroke. Conventional histological studies have shown that sweat glands are three-dimensionally coiled tubular structures consisting of ducts and secretory portions, although their detailed structural anatomy remains unclear. To better understand the details of the three-dimensional (3D) coiled structures of sweat glands, a whole-mount staining method was employed to visualize 3D coiled gland structures with sweat gland markers for ductal luminal, ductal basal, secretory luminal, and myoepithelial cells. Imaging the 3D coiled gland structures demonstrated that the ducts and secretory portions were comprised of distinct tubular structures. Ductal tubules were occasionally bent, while secretory tubules were frequently bent and formed a self-entangled coiled structure. Whole-mount staining of complex coiled gland structures also revealed the detailed 3D cellular arrangements in the individual sweat gland compartments. Ducts were composed of regularly arranged cuboidal shaped cells, while secretory portions were surrounded by myoepithelial cells longitudinally elongated along entangled secretory tubules. Whole-mount staining was also used to visualize the spatial arrangement of blood vessels and nerve fibers, both of which facilitate sweat secretion. The blood vessels ran longitudinally parallel to the sweat gland tubules, while nerve fibers wrapped around secretory tubules, but not ductal tubules. Taken together, whole-mount staining of sweat glands revealed the 3D cell shapes and arrangements of complex coiled gland structures and provides insights into the mechanical contraction of coiled gland structures during sweat secretion. PMID:28636607

Isotretinoin in lacrimal gland fluid and tears.

PubMed

Rismondo, V; Ubels, J L

1987-03-01

Isotretinoin (13-cis-retinoic acid) is used in the treatment of severe cystic acne. Adverse ocular reactions, including blepharoconjunctivitis and dry eye symptoms, are frequent side effects of this drug. Our previous observation that retinol is present in tears and lacrimal gland fluid suggests that isotretinoin may also be secreted by the lacrimal gland. Rabbits were treated with isotretinoin, and lacrimal gland fluid was collected from the cannulated lacrimal gland duct. Tears were collected from patients who were being treated with isotretinoin. Lacrimal gland fluid and tears were analyzed by reverse-phase high-pressure liquid chromatography and a peak eluted from each sample, which was identified as isotretinoin. We conclude that the lacrimal gland is able to secrete isotretinoin in addition to retinol and that, in animals and patients treated systemically with isotretinoin, the ocular surface is exposed to the drug via the tear film.

Salivary glands abnormalities in oculo-auriculo-vertebral spectrum.

PubMed

Brotto, Davide; Manara, Renzo; Vio, Stefania; Ghiselli, Sara; Cantone, Elena; Mardari, Rodica; Toldo, Irene; Stritoni, Valentina; Castiglione, Alessandro; Lovo, Elisa; Trevisi, Patrizia; Bovo, Roberto; Martini, Alessandro

2018-01-01

Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p < 0.001). Submandibular salivary gland hypoplasia was associated to Goldenhar phenotype (p < 0.05). Parotid gland abnormalities were associated with ipsilateral fifth (p < 0.001) and seventh cranial nerve (p = 0.001) abnormalities. No association was found between parotid gland anomaly and ipsilateral internal carotid artery, inner ear, brain, eye, or spine abnormalities (p > 0.6). Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment.

[Identification and preservation of parathyroid glands in cadaver parts].

PubMed

Melo, Catarina; Bernardes, António; Carvalho, Lina

2013-01-01

It is essential to know the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck in order to minimize the rate of thyroid surgery morbidity, especially the lesion of parathyroid glands and laryngeal nerves. The aim of this study was the identification of parathyroid glands in cadaver parts and their histological confirmation. Twenty cadaver parts were used to simulate thyroidectomies. During dissection, the thyroid glands and eventual parathyroid glands were isolated and then submitted to histological study. Twenty cadaver parts (anterior cervical organs) were used for macroscopic dissection during which 48 fragments that corresponded to eventual parathyroid glands were isolated, 35 of which were effectively confirmed through histological observation to be parathyroid glands. The 20 cadaver parts were then divided into three groups according to the number of histologically confirmed parathyroid glands. In the first group, composed of 11 cases, all eventual parathyroid glands were confirmed. In the second group, composed of six cases, only some glands were confirmed. In the third group, composed of three cases, none of the possible glands were confirmed. In seven of the 20 isolated thyroid glands, eight parathyroid glands were identified during histological study: four subcapsular, three extra-capsular, one intra-thyroidal. There was no statistical relation in the dimensions of the parathyroid glands. The knowledge of the anatomy of the central visceral compartment of the neck and its most frequent variations reduces but doesn't eliminate thyroid surgery morbidity, especially parathyroid iatrogenic excision, difficulty which has been demonstrated during the dissection of cadaver parts.

Pineal Gland Tumor but not Pinealoma: A Case Report.

PubMed

Naqvi, Syeda; Rupareliya, Chintan; Shams, Abdullah; Hameed, Maria; Mahuwala, Zabeen; Giyanwani, Pirthvi Raj

2017-08-18

The pineal gland is a small pinecone-shaped and functionally endocrine structure located in the epithalamus region. Developmentally, the pineal gland is considered as a part of the epithalamus. It plays a role in the entrainment of the circadian rhythms of an organism by producing melatonin, a functionally important hormone. Lesions of the pineal region are rare compared to other parts of the brain. A lesion may be tumorous or non-tumorous in nature. The most common lesions are tumors that are pineal parenchymal tumors (PPT) in origin. Gliomas are the second most common tumors in the pineal region. We report a case of a high-grade oligodendroglioma, not commonly seen in the pineal region, in a 45-year-old male. The patient was suspected to have a mass in the pineal region on a computed tomography (CT) scan and histology confirmed the diagnosis of oligodendroglioma. This is a unique case because only five such cases have been reported so far.

Calcium signalling in salivary gland physiology and dysfunction.

PubMed

Ambudkar, Indu S

2016-06-01

Studies over the past four decades have established that Ca(2+) is a critical factor in control of salivary gland function and have led to identification of the critical components of this process. The major ion transport mechanisms and ion channels that are involved in fluid secretion have also been established. The key event in activation of fluid secretion is an increase in [Ca(2+) ]i triggered by inositol 1,4,5-trisphosphate (IP3 )-induced release of Ca(2+) from ER via the IP3 receptor (IP3 R). IP3 Rs determine the site of initiation and the pattern of the [Ca(2+) ]i signal in the cell. However, Ca(2+) entry into the cell is required to sustain the elevation of [Ca(2+) ]i and fluid secretion and is mediated by the store-operated Ca(2+) entry (SOCE) mechanism. Orai1, TRPC1, TRPC3 and STIM1 have been identified as critical components of SOCE in these cells. Cells finely tune the generation and amplification of [Ca(2+) ]i signals for regulation of cell function. An important emerging area is the concept that unregulated [Ca(2+) ]i signals in cells can directly cause cell damage, dysfunction and disease. Alternatively, aberrant [Ca(2+) ]i signals can also amplify and increase the rates of cell damage. Such defects in Ca(2+) signalling have been described in salivary glands in conjunction with radiation-induced loss of salivary gland function as well as in the salivary defects associated with the autoimmune exocrinopathy Sjögren's syndrome. Such defects have been associated with altered function or expression of key Ca(2+) signalling components, such as STIM proteins and TRP channels. These studies offer new avenues for examining the mechanisms underlying the disease and development of novel clinical targets and therapeutic strategies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.

PubMed

Tan, Dun Xian; Xu, Bing; Zhou, Xinjia; Reiter, Russel J

2018-01-31

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye.

PubMed

Järvinen, Riikka L; Larmo, Petra S; Setälä, Niko L; Yang, Baoru; Engblom, Janne Rk; Viitanen, Matti H; Kallio, Heikki P

2011-09-01

Evaporative dry eye is associated with meibomian gland dysfunction and abnormalities of the tear film lipids. Dry eye is known to be affected positively by intake of linoleic and γ-linolenic acids and n-3 fatty acids. Oral sea buckthorn (Hippophaë rhamnoides) (SB) oil, which contains linoleic and α-linolenic acids and antioxidants, has shown beneficial effects on dry eye. The objective was to investigate whether supplementation with SB oil affects the composition of the tear film fatty acids in individuals reporting dry eye. One hundred participants were randomized to this parallel, double-blind, placebo-controlled study, which 86 of them completed. The participants daily consumed 2 g of SB or placebo oil for 3 months. Tear film samples were collected at the beginning, during, and at the end of the intervention and 1 to 2 months later. Tear film fatty acids were analyzed as methyl esters by gas chromatography. There were no group differences in the changes in fatty acid proportions during the intervention (branched-chain fatty acids: P = 0.49, saturated fatty acids: P = 0.59, monounsaturated fatty acids: P = 0.53, and polyunsaturated fatty acids: P = 0.16). The results indicate that the positive effects of SB oil on dry eye are not mediated through direct effects on the tear film fatty acids. Carotenoids and tocopherols in the oil or eicosanoids produced from the fatty acids of the oil may have a positive effect on inflammation and differentiation of the meibomian gland cells.

Neutron therapy for salivary and thyroid gland cancer

NASA Astrophysics Data System (ADS)

Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

2016-08-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Neutron therapy for salivary and thyroid gland cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gribova, O. V., E-mail: gribova79@mail.ru; Choynzonov, E. L., E-mail: nii@oncology.tomsk.ru; National Research Tomsk Polytechnic University, Lenina Avenue 30, Tomsk, 634050

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development

PubMed Central

Qu, Xiuxia; Pan, Yi; Carbe, Christian; Powers, Andrea; Grobe, Kay; Zhang, Xin

2012-01-01

Glycosaminoglycans (GAGs) play a central role in embryonic development by regulating the movement and signaling of morphogens. We have previously demonstrated that GAGs are the co-receptors for Fgf10 signaling in the lacrimal gland epithelium, but their function in the Fgf10-producing periocular mesenchyme is still poorly understood. In this study, we have generated a mesenchymal ablation of UDP-glucose dehydrogenase (Ugdh), an essential biosynthetic enzyme for GAGs. Although Fgf10 RNA is expressed normally in the periocular mesenchyme, Ugdh mutation leads to excessive dispersion of Fgf10 protein, which fails to elicit an FGF signaling response or budding morphogenesis in the presumptive lacrimal gland epithelium. This is supported by genetic rescue experiments in which the Ugdh lacrimal gland defect is ameliorated by constitutive Ras activation in the epithelium but not in the mesenchyme. We further show that lacrimal gland development requires the mesenchymal expression of the heparan sulfate N-sulfation genes Ndst1 and Ndst2 but not the 6-O and 2-O-sulfation genes Hs6st1, Hs6st2 and Hs2st. Taken together, these results demonstrate that mesenchymal GAG controls lacrimal gland induction by restricting the diffusion of Fgf10. PMID:22745308

Habenular commissure formation in zebrafish is regulated by the pineal gland-specific gene unc119c.

PubMed

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L; Gonzales, John; Burgess, Harold; Dawid, Igor B

2013-09-01

The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and, therefore, is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. Copyright © 2013 Wiley Periodicals, Inc.

Habenular commissure formation in zebrafish is regulated by the pineal gland specific gene unc119c

PubMed Central

Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L.; Gonzales, John; Burgess, Harold; Dawid, Igor B.

2013-01-01

Background The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and therefore is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Results Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. Conclusions We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. PMID:23749482

Rax: Developmental and Daily Expression Patterns in the Rat Pineal Gland and Retina

PubMed Central

Rohde, Kristian; Klein, David C.; Møller, Morten; Rath, Martin F.

2011-01-01

Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome. PMID:21749377

Warthin tumor arising from the minor salivary gland.

PubMed

Iwai, Toshinori; Baba, Junichi; Murata, Shogo; Mitsudo, Kenji; Maegawa, Jiro; Nagahama, Kiyotaka; Tohnai, Iwai

2012-09-01

Warthin tumor (WT) accounts for 4% to 13% of all salivary gland tumors. This benign tumor, which commonly arises in the parotid gland, is the second most common tumor of the salivary gland. WT is multicentric in 12% to 20% of patients and is bilateral in 5% to 14%. The mean age at diagnosis is 62 years (range, 12-92 years), and it rarely presents (<6%) before age 40 years. Extraparotid WT, arising from the submandibular gland or cervical lymph node for example, is very infrequent, with corresponding incidences of 0.4% to 6.9% and 8%, respectively. Moreover, WT arising from the minor salivary gland is extremely rare, with a reported incidence of merely 0.1% to 1.2%. We report here WT arising from the minor salivary gland in the buccal mucosa in a 66-year-old woman and review cases of WT of the minor salivary gland reported in the English literature.

Circadian Regulation of Pineal Gland Rhythmicity

PubMed Central

Borjigin, Jimo; Zhang, L. Samantha; Calinescu, Anda-Alexandra

2011-01-01

The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity. PMID:21782887

Diagnosis of dry eye disease and emerging technologies

PubMed Central

Zeev, Maya Salomon-Ben; Miller, Darby Douglas; Latkany, Robert

2014-01-01

Dry eye is one of the most commonly encountered problems in ophthalmology. Signs can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear break-up time, and meibomian gland disease. Current methods of diagnosis include a slit-lamp examination with and without different stains, including fluorescein, rose bengal, and lissamine green. Other methods are the Schirmer test, tear function index, tear break-up time, and functional visual acuity. Emerging technologies include meniscometry, optical coherence tomography, tear film stability analysis, interferometry, tear osmolarity, the tear film normalization test, ocular surface thermography, and tear biomarkers. Patient-specific considerations involve relevant history of autoimmune disease, refractive surgery or use of oral medications, and allergies or rosacea. Other patient considerations include clinical examination for lid margin disease and presence of lagophthalmos or blink abnormalities. Given a complex presentation and a variety of signs and symptoms, it would be beneficial if there was an inexpensive, readily available, and reproducible diagnostic test for dry eye. PMID:24672224

Outcomes of Thermal Pulsation Treatment for Dry Eye Syndrome in Patients With Sjogren Disease.

PubMed

Godin, Morgan R; Stinnett, Sandra S; Gupta, Preeya K

2018-04-26

To evaluate the clinical outcomes of thermal pulsation treatment in patients with meibomian gland dysfunction (MGD) and dry eye secondary to Sjogren disease. Twenty-four eyes from 13 patients with previously diagnosed Sjogren disease who presented to our institution with dry eye symptoms and had thermal pulsation treatment were prospectively followed up. Patients underwent comprehensive slit-lamp examination, including MGD grading, gland oil flow, corneal and conjunctival staining scores, and tear break-up time (TBUT). Tear osmolarity was tested before and after treatment. The average patient age was 62.4 years (range, 31-78 yrs); 12 were women and 1 a man. The average meibomian gland oil flow score showed an increase from pretreatment 0.71 to 1.75 at 1 year posttreatment (range 9-15 months) (P = 0.001). The average corneal staining score decreased from a pretreatment grade of 1.04 to a posttreatment grade of 0.36 (P < 0.001). The average conjunctival staining score decreased from a pretreatment grade of 1.5 to a posttreatment grade of 0.48 (P < 0.001). The average tear break-up time improved from 3.8 seconds before treatment to 7.5 seconds after thermal pulsation treatment (P < 0.001). There was no statistically significant change in the tear osmolarity or Ocular Surface Disease Index score. Our findings suggest that MGD is an important contributor to dry eye disease in patients with Sjogren disease and should not be overlooked when considering treatment options. Thermal pulsation is a therapeutic option for patients with Sjogren disease who have MGD and dry eye symptoms. After a single treatment, patients exhibited increased oil flow and tear break-up time with an associated decrease in corneal and conjunctival staining.

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRΔF508/ΔF508 Pigs

PubMed Central

Cho, Hyung-Ju; Joo, Nam Soo; Wine, Jeffrey J.

2011-01-01

Background Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion. Methodology/Principal Findings Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CFΔF508/ΔF508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands. Conclusions/Significance These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections. PMID:21935358

An historical view of the pineal gland and mental disorders.

PubMed

López-Muñoz, F; Molina, J D; Rubio, G; Alamo, C

2011-08-01

Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine). Copyright © 2011 Elsevier Ltd. All rights reserved.

Pituitary gland

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... should release by sending it either hormonal or electrical messages. In response to hormonal messages from the ... have properties similar to steroids In response to electrical messages from the hypothalamus, the pituitary gland releases ...

Cheilitis glandularis: immunohistochemical expression of protein water channels (aquaporins) in minor labial salivary glands.

PubMed

Nico, M M S; Melo, J N; Lourenço, S V

2014-03-01

Cheilitis glandularis (CG) is a rare condition in which thick saliva is secreted from dilated ostia of swollen minor salivary glands from the lips. Aquaporins (AQPs) are membrane proteins that exhibit channel activity specific for water and small solutes. AQPs are essential for corporal homeostasis, and are widely expressed through human tissues. Most AQPs studies are based on renal and nervous pathophysiology; few involve salivary glands. Some previous investigators hypothesized that minor salivary gland structure and function is normal on CG. To study possible salivary synthesis alterations in CG, we compared the expression of AQPs present in minor salivary glands in specimens with CG and controls by using immunohistochemistry.   Seven cases of CG and three normal controls were studied. Intensity and patterns of expression of AQP 1, 2 and 8 differed in CG compared with controls. AQP 4 and 5 (the most important AQP in salivary function) showed identical patterns in CG and controls. Our findings suggest that the expression and arguably, function of some of the AQPs may be altered in CG; consequently, water flow mechanism abnormalities with possible alteration in salivary composition seem to occur. External factors (mainly UV rays) seem to play an important role in CG; nonetheless, our findings suggest that there might be some degree of alteration on water transportation. © 2013 The Authors. Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

PubMed

Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

2016-10-01

Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

Secretion of a recombinant protein without a signal peptide by the exocrine glands of transgenic rabbits

PubMed Central

Iski, Gergely; Lipták, Nándor; Gócza, Elen; Kues, Wilfried A.; Bősze, Zsuzsanna

2017-01-01

Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB) transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG) promoter. Despite the absence of a signal peptide, the fluorophore protein was readily detected in milk, tear, saliva and seminal fluids. The expression pattern was verified by Western blot analysis. Mammary gland epithelial cells of SB-CAG-Venus transgenic lactating does also showed Venus-specific expression by tissue histology and fluorescence microscopy. In summary, the SB-CAG-Venus transgenic rabbits secrete the recombinant protein by different glands. This finding has relevance not only for the understanding of the biological function of exocrine glands, but also for the design of constructs for expression of recombinant proteins in dairy animals. PMID:29077768

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes

PubMed Central

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-01-01

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment. PMID:27272504

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes.

PubMed

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-06-07

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.

Irradiation doses on thyroid gland during the postoperative irradiation for breast cancer.

PubMed