scholarly journals [177Lu]Lu-PSMA-617 Salivary Gland Uptake Characterized by Quantitative In Vitro Autoradiography

2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Roswitha Tönnesmann ◽  
Philipp Meyer ◽  
Matthias Eder ◽  
Ann-Christin Baranski
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Tumor Control ◽  
Uptake Mechanism ◽  
Future Design ◽  
Gland Tissue ◽  
Specific Uptake ◽  
Therapy Strategies ◽  
Higher Doses

Irradiation of salivary glands remains the main dose-limiting side effect of therapeutic PSMA-inhibitors, especially when using alpha emitters. Thus, further advances in radiopharmaceutical design and therapy strategies are needed to reduce salivary gland uptake, thereby allowing the administration of higher doses and potentially resulting in improved response rates and better tumor control. As the uptake mechanism remains unknown, this work investigates the salivary gland uptake of [177Lu]Lu-PSMA-617 by autoradiography studies on pig salivary gland tissue and on PSMA-overexpressing LNCaP cell membrane pellets. Displacement studies were performed with non-labeled PSMA-617 and 2-PMPA, respectively. The uptake of [177Lu]Lu-PSMA-617 in glandular areas was determined to be partly PSMA-specific, with a high non-specific uptake fraction. The study emphasizes that [177Lu]Lu-PSMA-617 accumulation in pig salivary glands can be attributed to a combination of both specific and non-specific uptake mechanisms. The observation is of high impact for future design of novel radiopharmaceuticals addressing the dose-limiting salivary gland irradiation of current alpha endoradiotherapy in prostate cancer.

Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells

Pathobiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Naoyuki Matsumoto ◽  
Daisuke Omagari ◽  
Ryoko Ushikoshi-Nakayama ◽  
Tomoe Yamazaki ◽  
Hiroko Inoue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Salivary Gland ◽  
Tissue Injury ◽  
Ros Production ◽  
Oxygen Species ◽  
Saliva Secretion ◽  
Salivary Gland Tissue ◽  
Gland Tissue

<b><i>Introduction:</i></b> Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. <b><i>Methods:</i></b> Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase‐mediated dUTP nick‐end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. <b><i>Results:</i></b> In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2′-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. <b><i>Conclusion:</i></b> These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.

Mesenchymal control over elongating and branching morphogenesis in salivary gland development

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 209-221
Author(s):  
Hiroyuki Nogawa ◽  
Takeo Mizuno
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Submaxillary Gland ◽  
Branching Morphogenesis ◽  
Mouse Submaxillary Gland ◽  
Gland Development

Recombination of the epithelium and mesenchyme between quail anterior submaxillary gland (elongating type) and quail anterior lingual or mouse submaxillary gland (branching type) was effected in vitro to clarify whether the elongating morphogenesis was directed by the epithelial or the mesenchymal component. Quail anterior submaxillary epithelium recombined with quail anterior lingual or mouse submaxillary mesenchyme came to branch. Conversely, quail anterior lingual or 12-day mouse submaxillary epithelium recombined with quail anterior submaxillary mesenchyme came to elongate, though the mesenchyme was less effective with 13-day mouse submaxillary epithelium. These results suggest that the elongating or branching morphogenesis of quail salivary glands is controlled by the mesenchyme.

scholarly journals Organoid Models for Salivary Gland Biology and Regenerative Medicine

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Chen Zhao ◽  
Cuida Meng ◽  
Na Cui ◽  
Jichao Sha ◽  
Liwei Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Salivary Gland Tissue ◽  
Gland Tissue ◽  
Gland Function ◽  
Key Aspects ◽  
Complex Architecture

The salivary gland is composed of an elegant epithelial network that secrets saliva and maintains oral homeostasis. While cell lines and animal models furthered our understanding of salivary gland biology, they cannot replicate key aspects of the human salivary gland tissue, particularly the complex architecture and microenvironmental features that dictate salivary gland function. Organoid cultures provide an alternative system to recapitulate salivary gland tissue in vitro, and salivary gland organoids have been generated from pluripotent stem cells and adult stem/progenitor cells. In this review, we describe salivary gland organoids, the advances and limitations, and the promising potential for regenerative medicine.

scholarly journals Epigenetically quantified immune cells in salivary glands of Sjögren’s syndrome patients: a novel tool that detects robust correlations of T follicular helper cells with immunopathology

Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 335-343 ◽  
Author(s):  
Sofie L M Blokland ◽  
Fréderique M van Vliet-Moret ◽  
Maarten R Hillen ◽  
Aridaman Pandit ◽  
Roel Goldschmeding ◽  
...  
Keyword(s):  
Salivary Gland ◽  
B Cell ◽  
Salivary Glands ◽  
Immune Cells ◽  
Cell Counting ◽  
Tissue Cell ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Salivary Gland Tissue ◽  
Gland Tissue

Abstract Objective To investigate whether epigenetic cell counting represents a novel method to quantify immune cells in salivary glands of patients with different forms of Sjögren’s and sicca syndrome and to capture immunopathology and potentially aid in diagnosis. Methods DNA from frozen salivary gland tissue sections of sicca patients was used for bisulphite conversion of demethylated DNA cytosine residues, followed by cell-specific quantitative PCR to calculate cell percentages in relation to total tissue cell numbers as quantified by housekeeping gene demethylation. The percentages of epigenetically quantified cells were correlated to RNA expression of matched salivary gland tissue and histological and clinical parameters. Results The percentages of epigenetically quantified CD3, CD4, CD8, T follicular helper (Tfh) cells, FoxP3+ regulatory T cells and B cells were significantly increased in the salivary glands of patients with SS. Unsupervised clustering using these percentages identified patient subsets with an increased lymphocytic focus score and local B cell hyperactivity and classifies patients different from conventional classification criteria. In particular, Tfh cells were shown to strongly correlate with the expression of CXCL13, lymphocytic focus scores, local B cell hyperactivity and anti-SSA positivity. Conclusion Epigenetic cell counting is a promising novel tool to objectively and easily quantify immune cells in the labial salivary gland of sicca patients, with a relatively small amount of tissue needed. In view of the potential of this technique to include a huge number of (cell-specific) biomarkers, this opens up new standardized ways of salivary gland analysis with high relevance for patient classification, understanding of immunopathology and monitoring of drug responses in clinical trials.

scholarly journals Saliva and Blood Asprosin Hormone Concentration Associated with Obesity

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kader Ugur ◽  
Suleyman Aydin
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Weight Control ◽  
Normal Weight ◽  
Class Iii ◽  
Tissue Mass ◽  
Obese Class ◽  
Gland Tissue ◽  
Treatment Of Obesity ◽  
Normal Weight Control

Background. The aim was to investigate the amounts of saliva and serum asprosin in order to determine whether it is related to obesity and whether salivary glands synthesize asprosin or not.Methods. A total of 116 underweight, normal weight, overweight, and obese (class I, class II, and class III) volunteers participated in the study. Saliva and blood samples were collected simultaneously from the participants. The amounts of asprosin in saliva, salivary gland tissue supernatants, and bloods were determined by ELISA, whereas asprosin synthesis sites of salivary gland tissues were determined immunohistochemically.Results. The amount of asprosin from the lowest to the highest was in the order as follows: underweight, normal weight (control), overweight, and obese classes I and III. The lowest level of asprosin was detected in underweight individuals. It was also found that the interlobular striated ducts and the interlobular ducts of the submandibular and parotid salivary glands produce asprosin. According to these data, the asprosin level is related with obesity as the amount increases in accordance with increasing body mass index (BMI). On the other hand, there is also a relationship between the underweight and asprosin because the amount decreases with BMI decrease.Conclusions. Asprosin, a new adipokine, may be a novel indicator of adipose tissue mass. Therefore, we anticipate that antiasprosin preparations may be an alternative in the treatment of obesity in the future.

scholarly journals Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

2004 ◽  
Vol 72 (6) ◽  
pp. 3604-3608 ◽  
Author(s):  
Peter Preiser ◽  
Laurent Rénia ◽  
Naresh Singh ◽  
Bharath Balu ◽  
William Jarra ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Vaccine Development ◽  
Molecular Form ◽  
Mammalian Host ◽  
Phenotypic Differences ◽  
Apical Membrane Antigen 1 ◽  
Erythrocyte Binding ◽  
Development In Vitro

ABSTRACT MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.

The influence of various factors on fluid secretion by in vitro salivary glands of ixodid Ticks

1976 ◽  
Vol 64 (3) ◽  
pp. 727-742
Author(s):  
W. Kaufman
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Culture Medium ◽  
Dry Weight ◽  
Fluid Secretion ◽  
Ixodid Tick ◽  
Ixodid Ticks ◽  
Mammalian Tissue ◽  
Stimulating Factor

1. Salivary glands of the female ixodid tick, Dermacentor andersoni, secrete fluid in vitro when bathed in a slightly modified version of the mammalian tissue culture medium ‘TC 199′. 2. Rate of salivation in vitro increases with progression of feeding, but there is no comparable increase in dry weight of the salivary glands during the early phase of engorgement. Engorged ticks secreted at only 25% the rate of 90–250 mg ticks, indicating that salivary gland degeneration has already begun in the very early post-engorgement stage. 3. A salivary gland stimulating factor can be detected in the nervous system but not in other tissues. 4. Male salivary glands secrete at only 1/20th the rate of female glands. Thus males probably do not use their salivary glands as osmoregulatory organs. 5. From the uniform lack of response to ACh and uniform response to DA in 7 ixodid tick species, it is suggested that the control of salivation is similar throughout the ixodid family.

scholarly journals An ELISA to Detect Serum Antibodies to the Salivary Gland Toxin ofIxodes holocyclusNeumann in Dogs and Rodents

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
S. Hall-Mendelin ◽  
P. O'Donoghue ◽  
R. B. Atwell ◽  
R. Lee ◽  
R. A. Hall
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Negative Control ◽  
Mouse Bioassay ◽  
Parallel Testing ◽  
Experimental Infestation ◽  
Alternative Means ◽  
Purified Antigen ◽  
Control Antigen

TheIxodes holocyclustick causes paralysis in up to 10,000 companion and domestic animals each year in Australia. Treatment requires the removal of the parasite and the administration of a commercial tick antiserum that is prepared from hyperimmune dogs. Each batch of this serum is initially tested for toxin-neutralising potency in a mouse bioassay that is expensive, time consuming, and subjective. With the aim of developing a rapidin vitroassay to replace the bioassay, we used a partially purified antigen prepared fromI. holocyclussalivary glands to develop an ELISA to detect toxin-reactive antibodies in hyperimmune dog sera. The optimised ELISA reliably detected antibodies reactive toI. holocyclussalivary gland antigens. Parallel testing of sera with a negative control antigen prepared from the salivary glands of the nontoxic tickRhipicephalus(Boophilus)microplusprovided further evidence that we were detecting toxin-specific antibodies in the assay. Using the ELISA, we could also detect antibodies induced in rats after experimental infestation withI. holocyclus. This assay shows promise as an alternative means of assessing the potency of batches of hyperimmune dog serum and to screen for toxin-reactive monoclonal antibodies produced from immunised rodents.

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