Inducible nitric oxide synthase-mediated injury in a mouse model of acute salivary gland dysfunction.

AIM: Inducible nitric oxide synthase (iNOS) is a key regulator of the innate immune system. The aim of the current study was to explore whether innate immune-mediated iNOS and reactive nitrogen species acutely perturb acinar cell physiology and calcium homeostasis of exocrine salivary tissues. METHODS: Innate immunity in the submandibular gland of C57BL/6 mice was locally activated via intraductal retrograde infusion of polyinosinic:polycytidylic acid (poly (I:C). Expressions of iNOS and the activity of the reactive nitrogen species peroxynitrite, were evaluated by immunohistochemistry. Mice were pre-treated with the selective iNOS inhibitor aminoguanidine in order to substantiate the injurious effect of the nitrosative signal on the key calcium regulator sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2b) and calcium signalling. RESULTS: Challenging salivary gland innate immunity with poly (I:C) prompted upregulated expression of iNOS and the generation of peroxynitrite. Inhibition of iNOS/peroxynitrite revealed the role played by upregulated nitrosative signalling in: dysregulated expression of SERCA2b, perturbed calcium homeostasis and loss of saliva secretion. CONCLUSION: iNOS mediates disruption of exocrine calcium signalling causing secretory dysfunction following activation of innate immunity in a novel salivary gland injury model.

Bilateral subacute lacrimal gland enlargement mimicking dacryoadenitis in a 7-year-old boy: a rare adverse effect of valproic acid (sodium valproate).

A healthy 7-year-old boy presented with bilateral symmetrical lacrimal gland enlargement; a week later salivary gland enlargement was also noted. Clinical investigations suggested no diagnosis, and surgical biopsy was considered. Valproic acid (sodium valproate), which he was taking for absence seizures, has been reported to cause salivary gland swelling in adults. Suspecting that a similar mechanism could be causal, the drug was discontinued. Complete resolution of the lacrimal and salivary gland enlargement rapidly ensued. This is the first report of lacrimal gland enlargement caused by valproic acid.

Possible Drug-Associated Sialolithiasis From the Bicarbonate Anhydrase Inhibitor Topiramate: A Case Report and Literature Review.

Topiramate is an antiepileptic drug indicated for the treatment of seizure disorders, migraine prophylaxis, and, more recently, weight loss. This new indication will likely increase the use of this agent significantly. As a carbonic anhydrase inhibitor, topiramate can affect the pH of bodily fluids and is known to increase the risk of nephrolithiasis. However, as discussed in the present report, these properties also result in an as yet unaddressed risk of the development of sialoliths, calcified stones formed in the salivary duct or glands. The physiologic mechanisms for stone development in the salivary gland are reviewed and the pharmacologic effects of topiramate on sialolith formation discussed. The present report describes a female patient treated with topiramate for migraine prophylaxis who subsequently presented with a sialolith in the left submandibular duct.

Acute Submandibular Swelling Complicating Arteriography With Iodide Contrast: A Case Report and Literature Review.

Iodide mumps is an uncommon condition induced by iodide-containing contrast. We present the first reported case of iodide mumps in mainland China, which occurred after carotid artery intervention.The patient, a 65-year-old Chinese male, had a history of dizziness, hypertension, diabetes, and right arm weakness. He had no history of allergies and had never previously received iodide-containing contrast. The patient's kidney function and other laboratory findings were normal. He underwent stenting of the left internal carotid artery (LICA) opening and received approximately 250 mL of a nonionic contrast agent (ioversol). Approximately 5 hours after angioplasty, bilateral local swellings were noted near the mandible; the masses were moderately firm and nontender.Iodide mumps was diagnosed in the patient. Intravenous dexamethasone (10 mg) was administered. The submandibular glands had shrunk by 11 hours after angioplasty, and they gradually became softer. The mandibular salivary glands had completely recovered by 5 days after surgery.Iodide mumps represents a rare late reaction to iodine-containing contrast media. This condition can occur in any patient receiving any iodinated contrast agent and may recur upon repeated exposure, but self-resolution can be expected within 2 weeks. All clinicians who use contrast media or iodide should be aware of this condition.

[Mumps in a 80-year-old patient?]. / 80-jährige Patientin mit Mumps?

Iodide mumps is a bilateral swelling of the parotid glands which appears 1-2 days after the administration of iodated contrast material. It is caused by an iodide induced sialadenitis of parotid, submandibular or sublingual glands. The symptoms disappear spontaneously within one week is a rare complication Peripheral facial palsy. Therapeutic options are steroids or antihistamines, especially when there is an accompanying cutaneous vasculitis. This isn't a dangerous disease, but if diagnosed is made, unneccessary diagnostic investigations can be avoided.

The transduction of rat submandibular glands by an adenoviral vector carrying the human growth hormone gene is associated with limited and reversible changes at the infusion site.

Adenoviral vectors have been shown to efficiently deliver exogenous genes to salivary glands and have therefore been investigated as tools for the treatment of human disease. The purpose of this study was to evaluate the response of F344 rats to intraductal infusion of the right submandibular salivary gland with an adenoviral vector encoding the gene for human growth hormone (AdCMVhGH). Co-administration of hydroxychloroquine (HCQ) was used to redirect the secretion of human growth hormone (hGH) from saliva into serum. This paper documents the findings of the pathology evaluation of this National Toxicology Program study. The right submandibular salivary gland (infusion site) was the primary target organ, with microscopic lesions characteristic of a mild to moderate insult observed at 3 days post infusion in vector exposed animals. These lesions were characterized by variable degrees of acute glandular inflammation, degeneration and necrosis, with more severe lesions in the higher dose groups. Rats at 28 days post infusion had milder inflammation, degeneration and necrosis compared to day 3 rats, with variable degrees of regeneration. In conclusion, the effects on the salivary glands are reversible as indicated by the milder inflammation and degeneration in the day 28 rats concomitant with mild to moderate regeneration. Therefore, the vector appears relatively innocuous with limited tissue toxicity. [The supplemental data referenced in this paper is not printed in this issue of Toxicologic Pathology. It is available as a downloadable file in the online edition of Toxicologic Pathology, 34(4). In order to access the full article online, you must have either an individual subscription or a member subscription accessed through www.toxpath.org.].

Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects.

Sialadenosis has been defined as a non-inflammatory, parenchymatous salivary gland disease causing recurrent, bilateral swelling of the salivary glands. As an adverse drug reaction of valproic acid, sialadenosis is very rare. To our knowledge, it has been reported only once in the world literature to date. We present herein the case of a patient with valproic acid-associated sialadenosis of both the parotid and submandibular glands. This appears to be the first published case of a patient who received surgical treatment. On light and electron microscopy of all the affected salivary glands, granular sialadenosis with predominantly moderate electron-dense secretory cytoplasmatic granules was observed. No relevant degenerative alterations were seen. There was no histological evidence of peripheral neuropathy of the nerve supply, leading to disordered activity of acinar cells by loss of neurosecretory granules. Lateral parotidectomy, performed under neuromonitoring control for safety reasons, is the treatment of choice for chronic recurrent parotitis that does not respond to conservative therapy, particularly if the cosmetic deformity is unacceptable to the patient. If the submandibular glands are involved, partial removal is recommended.

Ultrasound findings of iodide mumps.

Iodide mumps, swelling of salivary glands after contrast medium injection, is a rare adverse reaction. We present a case in a 73-year-old man with advanced gastric cancer. About 10 min after a CT scan performed with intravenous injection of 140 ml of the low osmolality contrast agent Ioxaglate (Hexabrix 320, Guerbet, France), he complained of progressive swelling of the submandibular area. Ultrasound showed diffuse swelling and internal low echoic thick septa in the submandibular glands bilaterally. Approximately 1 h afterwards, the swelling of his submandibular glands started to regress and returned to normal within a day.

Captopril-induced bilateral parotid and submandibular sialadenitis.

Two cases of sialadenitis following treatment with captopril are described. In case 1, an upper chest and facial erythema and dryness of the mouth accompanied the swelling of the salivary glands. In case 2, a conjunctival erythema accompanied the sialadenitis. None of the patients had previously used captopril, and, in both cases, the swelling occurred within the first hour after the drug intake; the patients had a complete recovery within a few hours after captopril was withdrawn. It is possible that the reported effect was caused by a type-B idiosyncratic adverse drug reaction.

Induction of C-reactive protein, serum amyloid P component, and kininogens in the submandibular and lacrimal glands of rats with experimentally induced inflammation.

The mRNAs for acute-phase proteins and kininogens were found to be increased in the submandibular gland (SMG) and extraorbital and intraorbital lacrimal gland (ELG and ILG) in response to experimentally induced inflammation in rats; i.e., 24 hours after subcutaneous injection of turpentine oil, mRNAs for C-reactive protein (CRP), serum amyloid P component (SAP), and H- and T-kininogens were induced in the SMG, ELG, and ILG of rats, whereas these mRNAs were not detected in the same tissues of normal control rats. The induction of mRNAs for these inflammatory proteins by turpentine oil was preceded by a transient increase in the level of mRNA for tumor necrosis factor-alpha (TNF-alpha) at 6 hours after subcutaneous injection of the oil. This was confirmed by injection of another inflammation inducer, lipopolysaccharide (LPS), which induced the TNF-alpha mRNA in the same way at 6 hours as turpentine oil did. The up-regulation of acute-phase proteins including kininogens in the SMG, ELG, and ILG suggest the existence of a strict defense system in the exocrine glands.

[Inflammation of the salivary glands attributed to the use of nitrofurantoin]. / Ontsteking van de speekselklieren toegeschreven aan het gebruik van nitrofurantoïne.

In six patients, women of 49, 59, 71, 82, 76 and 64 years old, acute inflammation of parotid and submandibular salivary glands was diagnosed. All were using nitrofurantoin as treatment for urinary tract infection. The symptoms disappeared after the treatment was discontinued. There were no signs of hypersensitivity to nitrofurantoin. Three of the patients had similar complaints during previous treatment with nitrofurantoin.