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Concept: Salivary gland

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BACKGROUND: Canine Visceral Leishmaniasis (CVL) is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. METHODOLOGYPRINCIPAL FINDINGS: In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH) of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×10(7) parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×10(5) parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. CONCLUSION: The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission.

Concepts: Immune system, Saliva, Leishmaniasis, Leishmania, Glands, Salivary gland, Zoonosis, Phlebotominae

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Mumps is an acute viral disease characterized by fever and swelling of the parotid or other salivary glands. On May 1, 2015, the Illinois Department of Public Health (IDPH) confirmed a mumps outbreak at the University of Illinois at Urbana-Champaign. IDPH and the Champaign-Urbana Public Health District (C-UPHD) conducted an investigation and identified 317 cases of mumps during April 2015-May 2016. Because of sustained transmission in a population with high 2-dose coverage with measles-mumps-rubella (MMR) vaccine, a third MMR dose was recommended by IDPH, C-UPHD, and the university’s McKinley Health Center. No formal recommendation for or against the use of a third MMR dose has been issued by the Advisory Committee on Immunization Practices (ACIP) (1). However, CDC has provided guidelines for use of a third dose as a control measure during mumps outbreaks in settings in which persons are in close contact with one another, where transmission is sustained despite high 2-dose MMR coverage, and when traditional control measures fail to slow transmission (2).

Concepts: Epidemiology, Vaccination, MMR vaccine, Measles, Parotid gland, Salivary gland, Mumps, Advisory Committee on Immunization Practices

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The presence of the leptin receptor (ObR) has already been highlighted in the human major salivary glands and it has been hypothesized that leptin may act by regulating the gland’s growth. No data are reported on domestic animals so, considering the important role that these glands play, not only related to food ingestion and digestion, and the important functional role hypothesized to explain the presence of ObR in humans salivary glands, the aim of the present work was to investigate the presence and the distribution of the leptin receptor in horse parotid and mandibular glands, by immunohistochemical techniques. The presence of ObR was evidenced in parotid and mandibular glands, exclusively localized in duct epithelial cells; their positivity was localized in the cytoplasm and was most evident near its apical portion. Immuno-positivity not only affects the intralobular ducts (intercalated and striated) but also the interlobular ones. Our results indicate that horse major salivary glands, like those of humans, are likely targets of leptin actions, suggesting a functional role of leptin on these glands.

Concepts: Protein, Digestive system, Epithelium, Gland, Glands, Parotid gland, Salivary gland, Submandibular gland

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Sialolithiasis is a benign pathology that occurs most frequently in the submandibular salivary gland due to its anatomic features. Depending on the size and degree of calcification, a sialolith can be visible in radiographic examinations. Patients commonly experience pain and/or edema when the ducts are obstructed. The authors report two cases of sialolithiasis of the submandibular gland after searching for the source of swelling in the submandibular region. The diagnosis was confirmed by clinical and tomographic examinations. Despite the considerable size of the sialoliths, treatment consisted of the removal of the calcified mass using an intraoral surgical approach. The prognosis is often good and there is generally no recurrence of the condition.

Concepts: Physician, Medical diagnosis, Autonomic nervous system, Oral and maxillofacial surgery, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland

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Background Chronic sialadenitis is one of the most frequent chronic complications after radioiodine (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 (SGS) taken before and at 5 yrs after a RAI ablation. Methods SGS was performed just before RIA (pre-SGS) and approximately 5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (US) 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 US and EF between the two SGS. Xerostomia were assessed and compared with the SGS findings. Results Worsening of the US 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 showed a worsening US for at least 1 of 4 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 1 of the 4 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 were 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). Conclusion About 20% of the salivary glands were dysfunctional on SGS at 5 years after a single RAI ablation, especially in patients who received higher doses of radioiodine. While parotid glands are more susceptible to I-131 related damage, xerostomia was more associated with submandibular gland dysfunction and the prevalence of dysfunctional salivary glands.

Concepts: Sjögren's syndrome, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland, Mumps, Serous fluid

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Salivary glands, although widely considered as typically exocrine, may also release specific proteins in an endocrine manner. However, endocrine release of salivary gland proteins is not generally acknowledged since the evidences are not easily demonstrable. Submandibular salivary glands (SMG) of male Syrian hamsters express male-specific secretory proteins (MSP) visible in SDS-PAGE of SMG extracts, as major bands and also detectable in immunoblots of whole-saliva and urine as low MSP crossreactions. We report here that MSP is localized in acinar cells of SMG and acute treatment with isoproterenol (IPR; non-specific β1/β2-adrenergic agonist) results in considerable release of MSP in SMG-saliva. Moreover, acute IPR treatment markedly depletes SMG-MSP in a dose- and time-dependent manner. However, MSP depleted from SMG, far exceeds that recovered in SMG-saliva. Blood, submandibular lymph nodes and kidney of IPR-treated males showed MSP crossreactions and SDS-PAGE of their urine revealed profuse MSP excretion; this was undetectable in IPR-treated-SMG-ablated males, confirming that a substantial amount of MSP depleted from SMG after IPR treatment enters circulation and is excreted in urine. Treatments with specific β1- or β2-adrenergic agonists also reduced SMG-MSP levels and resulted in copious urinary excretion of MSP. Co-treatments with specific β1/β2-blockers indicated that above effects of IPR, β1- and even β2-agonists are very likely mediated by β1-adrenoceptors. MSP’s detection by SDS-PAGE in urine after β-agonist treatment is a compelling and easily demonstrable evidence of release into circulation of a salivary gland protein. The possible means (endocrine-like or otherwise) of MSP’s release into circulation and significance of its presence in saliva, blood and urine of male hamsters are discussed.

Concepts: Blood, Secretion, Pancreas, Glands, Hamster, Salivary gland, Exocrine system, Submandibular gland

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Sanguivorous leeches are ectoparasites having access to body fluids of potential hosts only infrequently. During feeding, salivary proteins are released from unicellular salivary glands into the wound. These substances, among them anti-coagulants, anti-inflammatory or anti-microbial agents, allow these animals proper feeding and long-term storage of host blood in their crops for several months. Using histological, protein biochemical and molecular techniques, we investigated whether synthesis of salivary proteins and refilling of salivary gland cells occur immediately after feeding or later when stored nutrients in the crop are getting scarce. The results of the histological analyses showed that gland cell area was significantly smaller right after feeding when compared with those in unfed animals. This parameter recovered quickly and reached the control level at 1 week after feeding. 2D gel electrophoresis and analysis of the abundance of individual proteins in extracts of leech tissues revealed that a subset of proteins that had been present in extracts of unfed animals virtually disappeared during feeding, but re-appeared within 1 week of feeding (most probably secretory proteins) while another subset did not change during the experimental period (most probably housekeeping proteins). Semi-quantitative PCR analysis of hirudin cDNA prepared from leech RNA samples revealed that the amount of hirudin transcripts increased immediately after feeding, peaked at 5 days after feeding and declined to control values thereafter. Our results indicate that bloodsucking leeches synthesize salivary proteins and refill their salivary gland cell reservoirs within a week of a blood meal to be prepared for another feeding opportunity.

Concepts: DNA, Protein, Molecular biology, Gel electrophoresis, Glands, Salivary gland, Leech, Hematophagy

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Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells and detected in saliva. Pathophysiological roles for salivary exosomes are beginning to be recognized in diseases including cancer, highlighting potential biomarkers and biological functions. Since early detection of cancer is vital for successful treatment, salivary exosomes would be advantageous in achieving a better survival rate due to their ready availability and noninvasiveness. The use of salivary exosomes may therefore be promising in the accurate detection of premalignant lesions and early-stage cancers, also for better our understanding of the molecular basis of tumorigenesis. In this chapter, we review our current knowledge of salivaomics, focusing on nucleic acids and proteins in saliva as potential cancer biomarkers. Since salivaomics is a rapidly evolving field, we hope to expand frameworks toward salivary exosomes, integrate new and existing information, and bridge salivaomics with other biomedical researches. Furthermore, we would like to coin the term “saliva-exosomics” as the next-generation salivaomics. Our goal in this chapter is to provide the most updated information on cancer-derived exosomes in the saliva as natural carriers of biomarkers and signaling molecules. Major advances include definitive structure analysis and molecular characterization of salivary exosomes. We also highlight the exosome biogenesis and cargo trafficking mechanisms in which recent animal studies have expanded our understanding of exosome-mediated transfer of cancer-derived products from distal tumor to salivary gland. The potential roles of the salivary exosomes in cancer progression and immune surveillance are also addressed.

Concepts: DNA, Cancer, Saliva, Oncology, Cell membrane, Atom, Neoplasm, Salivary gland

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The proper ablation of any neoplasm of the head and neck requires the inclusion of linear and anatomic barrier margins surrounding the neoplasm. Extirpative surgery of the major and minor salivary glands is certainly no exception to this surgical principle. To this end, the selection and execution of the most appropriate ablative surgical procedure for a major or minor benign salivary gland neoplasm is an essential exercise in oral and maxillofacial surgery. Of equal importance is the intraoperative identification and preservation of the pseudocapsule surrounding the benign neoplasm. This article reviews these important elements specifically related to ablative surgery of benign neoplasms of the parotid, submandibular and minor salivary glands with strict attention to observed nomenclature.

Concepts: Benign tumor, Sjögren's syndrome, Oral and maxillofacial surgery, Glands, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland

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The most common tumour of salivary gland is pleomorphic adenoma (PA). They are benign, painless, can grow into big tumours but usually do not affect nerves or lymph nodes. PA most commonly occurs in the parotid gland but it may involve submandibular, lingual and minor salivary glands also. They can attain giant proportions and weigh several kilograms. We report a giant PA arising in the submandibular gland and treated by complete surgical excision without any complication. A female patient presented with a tumour in the submandibular region and front of neck with a history of more than 18 years. The weight of the resected mass was 4.35 kg. Patient’s fear of surgery and lack of awareness were the main reasons for her long-standing swelling. Such giant PAs of the submandibular gland are very rare in medical literature.

Concepts: Mass, Sjögren's syndrome, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland, Mumps, Serous fluid