Comparative diagnostic sensitivity of the substantia nigra transcranial sonography and salivary gland biopsy in patients with Parkinson’s disease

Parkinsons disease is a chronic neurodegenerative disease, the diagnosis of which remains challenging at the early stages, although clinical diagnostic criteria are developed. The diagnostic accuracy is only 58% for patients at early Parkinsons disease stages. The sensitivity and specificity of transcranial sonography of the substantia nigra used for Parkinsons disease verification is about 85% and 71%, respectively. It has been shown that the aggregates of -synuclein in the nerve fibers in major salivary glands may be seen in Parkinsons disease patients. The availability of the salivary glands for morphological study made it possible to investigate the approaches of the in vivo histological diagnosis of Parkinsons disease based on the detection of -synuclein aggregates in the nerve fibers innervating the glands. Aim: To evaluate and compare the sensitivity of transcranial sonography of the substantia nigra and sublingual salivary gland biopsy. Materials and methods: Six patients with clinically verified Parkinsons disease were enrolled. Evaluation of the neurological state using special scales, transcranial sonography of the substantia nigra and sublingual salivary gland biopsy was performed. Results: Mean age of patients was 59 [58; 60.7] years, mean disease duration period was 5 [3; 7.75] years and the mean HoehnYahr stage was 2.25 [2; 2.5]. Hyperechogenicity of the substantia nigra was found in 3 of 6 patients and the substantia nigra sensitivity was shown to be 50%. Sublingual salivary gland biopsy was positive for -synuclein in 6 of 6 patients and the sensitivity of method was shown to be 100%. No adverse events after biopsy were registered. Conclusion: The sensitivity of sublingual salivary gland biopsy was higher than those of transcranial sonography of the substantia nigra, which indicates the prospect of using the biopsy method as a more sensitive diagnostic tool in Parkinsons disease (1 table, bibliography: 19 refs)

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Alpha-synuclein in salivary gland as biomarker for Parkinson’s disease

Reviews in the Neurosciences ◽

10.1515/revneuro-2018-0064 ◽

2019 ◽

Vol 30 (5) ◽

pp. 455-462 ◽

Cited By ~ 4

Author(s):

Flaminia Campo ◽

Raffaella Carletti ◽

Massimo Fusconi ◽

Clelia Pellicano ◽

Francesco E. Pontieri ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Salivary Gland ◽

Salivary Glands ◽

Submandibular Gland ◽

Alpha Synuclein ◽

Minor Salivary Glands ◽

Mesh Terms ◽

Salivary Gland Biopsy

Abstract Estimates of the accuracy of clinical diagnosis of Parkinson’s disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: ‘salivary gland biopsy for PD’, ‘PD and dysphagia’, ‘alpha-synuclein and salivary gland’. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

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Direct in vivo adenovirus-mediated gene transfer to salivary glands

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.266.6.g1146 ◽

1994 ◽

Vol 266 (6) ◽

pp. G1146-G1155 ◽

Cited By ~ 6

Author(s):

A. Mastrangeli ◽

B. O'Connell ◽

W. Aladib ◽

P. C. Fox ◽

B. J. Baum ◽

...

Keyword(s):

Salivary Gland ◽

Gene Transfer ◽

Salivary Glands ◽

De Novo ◽

Recombinant Adenovirus ◽

Salivary Gland Cell ◽

Immunodeficient Mice ◽

Ductal Cells ◽

Adenovirus Vectors

Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSV beta gal [coding for the intracellular protein beta-galactosidase (beta-Gal)] and Ad alpha 1AT [coding for human alpha 1-antitrypsin (alpha 1-AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSV beta gal vector to rat salivary glands in vivo resulted in beta-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Ad alpha 1AT resulted in expression of alpha 1-AT mRNA transcripts, de novo synthesis of alpha 1-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSV beta gal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated beta-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications.

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Diagnostic Value of Salivary Gland Ultrasonographic Scoring System in Primary Sjögren’s Syndrome: A Comparison with Scintigraphy and Biopsy

The Journal of Rheumatology ◽

10.3899/jrheum.081267 ◽

2009 ◽

Vol 36 (7) ◽

pp. 1495-1500 ◽

Cited By ~ 68

Author(s):

VERA D. MILIC ◽

RADMILA R. PETROVIC ◽

IVAN V. BORICIC ◽

JELENA MARINKOVIC-ERIC ◽

GORAN L. RADUNOVIC ◽

...

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Scoring System ◽

Sjogren’S Syndrome ◽

Diagnostic Value ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Salivary Gland Biopsy

Objective.To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren’s syndrome (SS).Methods.In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0–48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients’ total scintigraphic score (0–12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system.Results.Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients.Conclusion.We show high diagnostic accuracy of a novel US scoring system of salivary glands (0–48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy.

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In vivo detection of iron and neuromelanin by transcranial sonography – a new approach for early detection of substantia nigra damage

Journal of Neural Transmission ◽

10.1007/s00702-005-0447-5 ◽

2006 ◽

Vol 113 (6) ◽

pp. 775-780 ◽

Cited By ~ 44

Author(s):

D. Berg

Keyword(s):

Early Detection ◽

Substantia Nigra ◽

Transcranial Sonography ◽

New Approach ◽

In Vivo Detection

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Secondary Sjögren's in patients with systemic scleroderma

Medical alphabet ◽

10.33667/2078-5631-2019-3-23(398)-37-39 ◽

2019 ◽

Vol 3 (23) ◽

pp. 37-39

Author(s):

E. I. Selifanova ◽

M. S. Esayan

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Minor Salivary Gland ◽

Systemic Scleroderma ◽

Minor Salivary Glands ◽

Minor Salivary Gland Biopsy ◽

European Consensus ◽

Salivary Gland Biopsy ◽

Morphological Differences ◽

Lymphoid Infiltration

The aim of the study was to investigate the morphological differences of the minor salivary glands in patients with secondary Sjögren's syndrome associated with systemic scleroderma (Scl-SS). Total of 40 patients were grouped according to the American–European Consensus Group criteria. Information about the duration of the disease was taken from the patients records. Sections of the minor salivary gland biopsy were reevaluated, and the lymphocyte focus score (FS), plasma cell focus, and fibrosis rates were all evaluated. The groups were formed according to the duration of the disease: less than and over 5 years.Results. Scl-SS leads to changes in both in the large salivary glands and in the MSG, manifested in the form of mucoid swelling, fibrinoid changes, hyalinosis and sclerosis. In patients with Scl-SS the progression of the process leads to the destruction of the duct wall and to the focal and diffuse lymphoid infiltration.

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Developmentally regulated infectivity of malaria sporozoites for mosquito salivary glands and the vertebrate host.

Journal of Experimental Medicine ◽

10.1084/jem.175.6.1607 ◽

1992 ◽

Vol 175 (6) ◽

pp. 1607-1612 ◽

Cited By ~ 48

Author(s):

M G Touray ◽

A Warburg ◽

A Laughinghouse ◽

A U Krettli ◽

L H Miller

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Blood Meal ◽

Immunofluorescence Assay ◽

Circumsporozoite Protein ◽

Vertebrate Host ◽

Mosquito Vector ◽

Mosquito Salivary Gland ◽

Uninfected Female

Sporozoites are an invasive stage of the malaria parasite in both the mosquito vector and the vertebrate host. We developed an in vivo assay for mosquito salivary gland invasion by preparing Plasmodium gallinaceum sporozoites from infected Aedes aegypti mosquitoes under physiological conditions and inoculating them into uninfected female Ae. aegypti. Sporozoites from mature oocysts were isolated from mosquito abdomens 10 or 11 d after an infective blood meal. Salivary gland sporozoites were isolated 13 or 14 d after an infective blood meal. Purified oocyst sporozoites that were inoculated into uninfected female mosquitoes invaded their salivary glands. Using the same assay system, sporozoites derived from salivary glands did not reinvade the salivary glands after inoculation. Conversely, as few as 10 to 50 salivary gland sporozoites induced infection in chickens, while only 2 of 10 chickens inoculated with 5,000 oocyst sporozoites were infected. Both sporozoite populations were found to express a circumsporozoite protein on the sporozoite surface as determined by immunofluorescence assay and circumsporozoite precipitation test using a circumsporozoite protein-specific monoclonal antibody. We conclude that molecules other than this circumsporozoite protein may be responsible for the differential invasion of mosquito salivary glands or infection of the vertebrate host.

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Laminin-1 Peptides Conjugated to Fibrin Hydrogels Promote Salivary Gland Regeneration in Irradiated Mouse Submandibular Glands

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.729180 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kihoon Nam ◽

Harim T. dos Santos ◽

Frank Maslow ◽

Bryan G. Trump ◽

Pedro Lei ◽

...

Keyword(s):

Radiation Therapy ◽

Salivary Gland ◽

Salivary Glands ◽

Tissue Regeneration ◽

Secretory Function ◽

Gland Morphogenesis ◽

Salivary Gland Regeneration ◽

Laminin 1

Previous studies demonstrated that salivary gland morphogenesis and differentiation are enhanced by modification of fibrin hydrogels chemically conjugated to Laminin-1 peptides. Specifically, Laminin-1 peptides (A99: CGGALRGDN-amide and YIGSR: CGGADPGYIGSRGAA-amide) chemically conjugated to fibrin promoted formation of newly organized salivary epithelium both in vitro (e.g., using organoids) and in vivo (e.g., in a wounded mouse model). While these studies were successful, the model’s usefulness for inducing regenerative patterns after radiation therapy remains unknown. Therefore, the goal of the current study was to determine whether transdermal injection with the Laminin-1 peptides A99 and YIGSR chemically conjugated to fibrin hydrogels promotes tissue regeneration in irradiated salivary glands. Results indicate that A99 and YIGSR chemically conjugated to fibrin hydrogels promote formation of functional salivary tissue when transdermally injected to irradiated salivary glands. In contrast, when left untreated, irradiated salivary glands display a loss in structure and functionality. Together, these studies indicate that fibrin hydrogel-based implantable scaffolds containing Laminin-1 peptides promote secretory function of irradiated salivary glands.

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THE ROLE OF SALIVARY GLAND BIOPSY IN DIAGNOSIS OF SYSTEMIC DISEASES AND THEIR LYMPHOPROLIFERATIVE COMPLICATIONS

Российский стоматологический журнал ◽

10.18821/1728-2802-2017-21-4-218-224 ◽

2017 ◽

Vol 21 (4) ◽

pp. 218-224

Author(s):

Ekaterina Borisovna Rodionova

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Malignant Tumors ◽

Diagnostic Value ◽

Pathological Process ◽

Al Amyloidosis ◽

Biliary Cirrhosis ◽

Systemic Diseases ◽

Viral Hepatitis C ◽

Salivary Gland Biopsy

The clinical picture of many systemic diseases (SD) could make its debut in the maxillofacial area with salivary gland lesions. Sjogren’s sicca syndrome, IgG4-related diseases, sarcoidosis, viral hepatitis - C, primary biliary cirrhosis, autoimmune hepatitis, as well as complications of the plurality of abnormalities in the form of lymphoproliferative diseases including AL-amyloidosis and B-cell lymphomas of different malignant tumors. The main diagnostic criteria in this case are the data of histological and immunohistochemistry studies of affected tissues. The aim of this publication is to analyze literature data on the pathological changes developing in salivary glands at different SD. The question about the diagnostic value of limphoplazmatsitarny infiltrate detected in the salivary gland biopsy materials SD and its influence on the prognosis and course of pathological process remains open. Conclusions: salivary glands biopsy has played a significant role in the early diagnosis and follow-up of patients with a variety of SD occurring with salivary gland lesions and such research studies have been required to continue.

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A Novel Experimental Approach for In Vivo Analyses of the Salivary Gland Microvasculature

Frontiers in Immunology ◽

10.3389/fimmu.2020.604470 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bernd Uhl ◽

Constanze Braun ◽

Julian Dominik ◽

Joshua Luft ◽

Martin Canis ◽

...

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Experimental Approach ◽

Immune Cell ◽

Microvascular Dysfunction ◽

Tissue Sections ◽

Immune Cell Subsets ◽

Microscopy Techniques ◽

And Control

Microvascular dysfunction plays a fundamental role in the pathogenesis of salivary gland disorders. Restoring and preserving microvascular integrity might therefore represent a promising strategy for the treatment of these pathologies. The mechanisms underlying microvascular dysfunction in salivary glands, however, are still obscure, partly due to the unavailability of adequate in vivo models. Here, we present a novel experimental approach that allows comprehensive in vivo analyses of the salivary gland microvasculature in mice. For this purpose, we employed different microscopy techniques including multi-photon in vivo microscopy to quantitatively analyze interactions of distinct immune cell subsets in the submandibular gland microvasculature required for their infiltration into the surrounding parenchyma and their effects on microvascular function. Confocal microscopy and multi-channel flow cytometry in tissue sections/homogenates complemented these real-time analyses by determining the molecular phenotype of the participating cells. To this end, we identified key adhesion and signaling molecules that regulate the subset- and tissue-specific trafficking of leukocytes into inflamed glands and control the associated microvascular leakage. Hence, we established an experimental approach that allows in vivo analyses of microvascular processes in healthy and diseased salivary glands. This enables us to delineate distinct pathogenetic factors as novel therapeutic targets in salivary gland diseases.

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