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Drug Metabolism and Disposition: the... May 2024Heart failure (HF) is a chronic disease affecting 1-2% of the global population. I-labeled -iodobenzylguanidine (mIBG) is FDA-approved for cardiac imaging and prognosis...
Heart failure (HF) is a chronic disease affecting 1-2% of the global population. I-labeled -iodobenzylguanidine (mIBG) is FDA-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. and mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, adrenal gland). No difference was observed in overall plasma exposure between mice. Strikingly, cardiac mIBG was depleted in mice, resulting in 83% reduction in overall cardiac exposure (AUC: 12.7 versus 2.1 µghr/g). mIBG tissue exposure (AUC) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung respectively in mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo; and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. I-mIBG is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that mIBG tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, we have demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Our findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG imaging and further suggest OCT3 as a risk factor for disease progression in heart failure patients.
PubMed: 38811159
DOI: 10.1124/dmd.124.001709 -
Cancer Treatment and Research... May 2024Adenoid cystic carcinoma (ACC) of the salivary glands has poor long-term prognosis and a high metastatic rate. Toll-like receptors (TLRs), first-line immune activators,...
OBJECTIVES
Adenoid cystic carcinoma (ACC) of the salivary glands has poor long-term prognosis and a high metastatic rate. Toll-like receptors (TLRs), first-line immune activators, have been associated with both tumor progression and suppression. We aimed to study TLR3 and TLR7 behavior in ACC.
MATERIALS AND METHODS
We studied TLR3 and TLR7 immunoexpression of 46 minor salivary gland ACCs diagnosed at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland over the period 1974-2012. The associations of TLR3 and TLR7 immunoexpression with clinicopathological factors were evaluated by χ-test and Fisher's exact test.
RESULTS
In the majority of samples, both TLR3 and TLR7 were immunoexpressed in cytoplasm. The immunoexpression was heterogeneous between individual tumors. Stronger TLR7 immunoexpression associated with recurrence rate and poorer disease-specific survival (DSS). TLR3 did not associate significantly with survival although we found an inverse correlation between TLR3 and TLR7 immunopositivity. Hence, when TLR3 immunoexpression was negative or mild, TLR7 immunoexpression was moderate to strong, and vice versa.
CONCLUSIONS
TLR3 and TLR7 are immunoexpressed in minor salivary gland ACC. TLR7 is potentially an independent prognostic marker for recurrence rate and DSS.
PubMed: 38810370
DOI: 10.1016/j.ctarc.2024.100822 -
CoDAS 2024To verify the immediate effects of photobiomodulation on the production of salivary flow and the correlation of demographic, anthropometric and medication use data. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To verify the immediate effects of photobiomodulation on the production of salivary flow and the correlation of demographic, anthropometric and medication use data.
METHODS
The study included 100 healthy individuals, aged between 18 and 76 years (mean 27.2 years), randomly split into an experimental group and a placebo group. Assessments of anthropometric measurements, self-perception of saliva production and sialometry were performed. Next, LASER irradiation was carried out at an infrared wavelength (808 nanometers) with 100 milliwatts (mw) of power at five intraoral points: on the sublingual glands and bilaterally on the submandibular and parotid glands, at doses of 9, 18 and 24 joules (J). Sialometry was repeated after each application. The control group received the same procedures with placebo equipment.
RESULTS
There was a statistical association in the self-perception of reduced saliva in the experimental group for the 24J dose and in sialometry and in the reduction in salivary flow for the 18J and 24J doses and an increase to 9J, in both groups. There was no association when comparing the experimental and placebo groups. Multiple multinomial regression analysis revealed that the reduction or increase in salivary flow is independent of demographic, anthropometric and medication use variables.
CONCLUSION
The bioinhibitory action of photobiomodulation on healthy salivary glands occurred at a dose of 18J and 24J, while the biostimulant action happened at a dose of 9J, regardless of demographic, anthropometric variables and medication use. The self-perception of reduced salivary flow occurred at 24J.
Topics: Humans; Adult; Low-Level Light Therapy; Middle Aged; Adolescent; Young Adult; Male; Female; Saliva; Aged; Salivation; Salivary Glands
PubMed: 38808859
DOI: 10.1590/2317-1782/20242023224pt -
BMC Oral Health May 2024This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. (Comparative Study)
Comparative Study
OBJECTIVE
This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate.
METHODS
One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test.
RESULTS
Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively.
CONCLUSION
GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.
Topics: Animals; Rats; Xerostomia; Parotid Gland; Ki-67 Antigen; Methotrexate; Gum Arabic; Thiophenes; Caspase 3; Male; Rats, Wistar; Quinuclidines
PubMed: 38807094
DOI: 10.1186/s12903-024-04374-8 -
Seminars in Arthritis and Rheumatism Aug 2024To assess whether addition of the salivary gland ultrasonography (SGUS) OMERACT score influences the performance of the 2016 ACR/EULAR classification criteria for...
OBJECTIVES
To assess whether addition of the salivary gland ultrasonography (SGUS) OMERACT score influences the performance of the 2016 ACR/EULAR classification criteria for Sjögren's disease (SjD) in daily clinical practice.
METHODS
Patients visiting the Sjögren Expertise centre in the University Medical Center Groningen for a diagnostic trajectory because of a suspicion of SjD were included. SGUS was performed of both parotid and submandibular glands. ROC analysis was used to assess the accuracy to predict clinical diagnosis of SjD with the SGUS OMERACT score, and by adding the SGUS OMERACT score to the ACR/EULAR criteria. Furthermore, the performance of the SGUS OMERACT and total SGUS Hocevar score were compared.
RESULTS
In total, 419 consecutive patients were included. ROC analysis of the highest SGUS OMERACT score out of all four salivary glands (range 0-3) showed good accuracy (AUC 0.849) to predict clinical diagnosis of SjD, comparable to the accuracy of the total SGUS OMERACT score (range 0-12; AUC 0.868) and total Hocevar score (range 0-48; AUC 0.864). When incorporating the highest SGUS OMERACT score (cut-off score of ≥2) as additional item in the ACR/EULAR criteria, accuracy remained excellent (AUC 0.974), and clinical diagnosis could be predicted with a sensitivity of 96.4% and specificity of 86.5%.
CONCLUSION
The accuracy of the ACR/EULAR classification criteria for predicting the clinical diagnosis of SjD remained excellent after incorporating the SGUS OMERACT score and extends the diagnostic options in patients suspected with SjD.
Topics: Humans; Ultrasonography; Female; Middle Aged; Male; Salivary Glands; Sjogren's Syndrome; Aged; Adult; Severity of Illness Index
PubMed: 38805898
DOI: 10.1016/j.semarthrit.2024.152473 -
BMC Cancer May 2024This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with...
Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.
BACKGROUND
This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC).
METHODS
Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses.
RESULTS
Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (D) and V of parotid glands; D and V of submandibular glands; and D of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The D of the parotid and sublingual glands was a risk factor for xerostomia. The D of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia.
CONCLUSIONS
Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.
Topics: Humans; Deglutition Disorders; Male; Xerostomia; Female; Nasopharyngeal Carcinoma; Middle Aged; Radiotherapy, Intensity-Modulated; Retrospective Studies; Follow-Up Studies; Nasopharyngeal Neoplasms; Adult; Aged; Radiation Injuries; Deglutition; Salivary Glands; Radiotherapy Dosage; Prognosis; Young Adult
PubMed: 38802747
DOI: 10.1186/s12885-024-12391-7 -
Journal of Oral and Maxillofacial... 2024c-KIT is an important diagnostic marker in salivary gland tumours and is expressed in most adenoid cystic carcinomas. Histologically similar salivary gland tumours with... (Review)
Review
c-KIT is an important diagnostic marker in salivary gland tumours and is expressed in most adenoid cystic carcinomas. Histologically similar salivary gland tumours with variable immunohistochemical expression for c-KIT pose a challenge and make diagnostic reliability ambivalent. An electronic search was performed in MEDLINE by PubMed, Google Scholar, Scopus, Trip, Cochrane Library, and EMBASE up to 31 December 2023, without period restriction. The articles that investigated CD117 or c-KIT in salivary gland tumours were included for review. Sensitivity, specificity, and positive and negative predictive values of c-KIT immunohistochemical expressions were derived and subjected to meta-analysis using Open Meta analyst for Sierra software. The risk of bias in selected studies was analysed using the QUADAS-2 tool, and RevMan 5.4 was used to output the result. Forty-three articles were reviewed, and 2285 salivary gland cases were analysed. Adenoid cystic carcinoma had an overall expression of 84.9%. A similar expression was found in epimyoepithelial carcinoma (79.1%), lymphoepithelial carcinoma (75%), myoepithelial carcinoma (60.8%), monomorphic adenoma (94.1%), and pleomorphic adenoma (74.7%). The sensitivity, specificity, and positive and negative predictive values of c-KIT/CD117 for adenoid cystic carcinoma with other salivary gland tumours were 84.99%, 69.09%, 84.79%, and 69.41%, respectively. Current evidence shows that c-KIT, despite its sensitivity, is not specific and therefore cannot be a useful diagnostic marker for distinguishing adenoid cystic carcinoma from other salivary gland tumours. Further research on other salivary gland tumours that exhibit comparable expression is necessary to validate the diagnostic accuracy of c-KIT.
PubMed: 38800447
DOI: 10.4103/jomfp.jomfp_70_24 -
Journal of Oral and Maxillofacial... 2024Low-grade intraductal carcinoma (LG-IC), is a rare malignant tumour of the salivary glands which has a very good prognosis and must be differentiated from the other...
RATIONALE
Low-grade intraductal carcinoma (LG-IC), is a rare malignant tumour of the salivary glands which has a very good prognosis and must be differentiated from the other types of salivary gland malignant tumours, which have a totally different behaviour and a worse prognosis.
PATIENT CONCERNS
A case is presented of a 52-year-old woman who was first diagnosed and treated in another clinic in 2019 for an LG-IC in the left submandibular gland space. Two years later, she was admitted to our department with a new lesion, this time in the upper jaw lip on the left side, which also turned out to be LG-IC.
DIAGNOSIS
Magnetic resonance imaging and positron emission tomography-computed tomography were performed in order to diagnose and adequately stage the disease prior to the therapeutic intervention.
OUTCOMES
A 6-month follow-up reveals no sign of recurrence.
TAKEAWAY LESSONS
Literature on this rare histopathological entity, as well as the differential diagnosis with the other malignant lesions of the salivary glands and the frequency of metastasis, were reviewed.
PubMed: 38800436
DOI: 10.4103/jomfp.jomfp_500_22 -
Journal of Oral and Maxillofacial... 2024Pleomorphic adenoma (PA) is a benign epithelial tumour originating from the salivary gland, specifically the parotid gland. This study aims to comprehensively analyse...
INTRODUCTION
Pleomorphic adenoma (PA) is a benign epithelial tumour originating from the salivary gland, specifically the parotid gland. This study aims to comprehensively analyse the clinical and pathological features of PA by examining the characteristics of the tumour, including its histological structure and immunohistochemical profile.
MATERIALS AND METHODS
Over 8 years, beginning in October 2015 and ending in October 2023, an exhaustive retrospective study was conducted in the Department of Pathology, Kasturba Medical College, Mangalore, Manipal University, Karnataka, India. The research focused on 100 cases of pleomorphic adenoma and involved a meticulous examination of the clinical and pathological characteristics obtained by retrieving the pertinent files.
RESULTS
Out of all the primary tumours, the majority ( = 70) was found in the parotid gland, followed by PA that developed from the minor salivary glands of the palate ( = 07), the submandibular gland ( = 17), and the lacrimal gland ( = 04). Only two cases had a primary tumour located in the lips. Females were more susceptible to these tumours than males. The parotid gland tumours showed a distinct trend in laterality, with 73 cases observed on the right side. In 85%, the initial symptom of the condition was painless swelling.
CONCLUSION
Salivary gland PA is typically a benign tumour. However, a subset of these tumours can exhibit a malignant phenotype. The preferred treatment is surgical excision with adequate margins.
PubMed: 38800432
DOI: 10.4103/jomfp.jomfp_452_23 -
Radiology Case Reports Aug 2024Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with...
Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with lung metastases on which F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) was performed. We report the case of a 57-year-old Japanese woman with an adenoid cystic carcinoma of the sublingual gland with lung metastases in whom the FDG uptake of the lung metastasis was low despite high FDG uptake in the primary lesion. The pathological examination revealed that solid components were more visible and the Ki-67 index was more positive in the primary lesion compared to the metastatic lesion. We speculate that differences in tumor growth ability might have resulted in the differences in FDG uptake. This case demonstrates that significant differences might occur in the FDG uptake between primary and metastatic tumors.
PubMed: 38800080
DOI: 10.1016/j.radcr.2024.04.037