Submandibular Gland Pathogenesis Following SARS-CoV-2 Infection and Implications for Xerostomia.

Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1ß were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1ß immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.

CFTR expression in human salivary gland acinar cells.

The key role of CFTR in secretory epithelia has been extensively documented. Additionally, CFTR plays a significant role in ion absorption in exocrine glands, including salivary and sweat glands. Most of the knowledge about CFTR expression comes from animal models such as the mouse or the rat, but there is limited information about CFTR expression in human tissues. In the present study, we assessed the expression of CFTR in human submandibular and parotid glands. Consistent with findings in rodent salivary glands, our immunolocalization studies show that CFTR is expressed in duct cells. However, CFTR expression in human salivary glands differs from that in rodents, as immunolocalization and single-cell RNA sequencing analysis from a previous study performed in the human parotid gland revealed the presence of CFTR protein and transcripts within a distinct cell cluster. Based on cell marker expression, this cluster corresponds to acinar cells. To obtain functional evidence supporting CFTR expression, we isolated human parotid acinar cells through collagenase digestion. Acinar cells displayed an anion conductance that was activated in response to cAMP-increasing agents and was effectively blocked by CFTRInh172, a known CFTR blocker. This study provides novel evidence of CFTR expression within acinar cells of human salivary glands. This finding challenges the established model positioning CFTR exclusively in duct cells from exocrine glands.NEW & NOTEWORTHY This study addresses the uncertainty about the impact of CFTR on human salivary gland function. We found CFTR transcripts in a subset of duct cells known as ionocytes, as well as in acinar cells. Isolated human parotid acinar cells exhibited Cl- conductance consistent with CFTR activity. This marks the first documented evidence of functional CFTR expression in human salivary gland acinar cells.

Effect of pancreatin on acute pancreatitis resulting from L-arginine administration in mice, a morpho-histopathological and biochemical study

Abstract Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.

Síndrome de hipersecreción de lipasa y lesiones óseas en el cáncer de células acinares del páncreas / Lipase hypersecretion syndrome and bone lesions in acinar cell cancer of the pancreas. Report of one case

Lipase hypersecretion syndrome (LHS) is a rare paraneoplastic syndrome, associated with acinar cell carcinoma of the pancreas (ACCP) in 10% to 15% of patients. Clinically, LHS manifests itself with the appearance of subcutaneous fibrocystic nodules, associated with trophic changes in the overlying skin, such as ulcers or fistulas that are difficult to manage, mainly affecting the lower extremities. Additionally, lipolysis near the joints and in the intraosseous adipose tissue can cause bilateral arthralgias, especially of the knees and ankles. We report a 57-year-old man, with a history of insulin resistance and allergic rhinitis, who presented in June 2019 with multiple subcutaneous nodules in the lower extremities, predominantly in both ankles, associated with arthralgia in that region. Additionally, a CT scan of the abdomen revealed a significant abdominal mass, measuring approximately 17 cm and in contact with the body and tail of the pancreas, pathologically compatible with an ACCP. Treatment with capecitabine was started with a favorable progression. The patient currently presents a small left lateral retro malleolar fistula, which, given the analyzes, studies and reviewed literature is concluded to be a lesion in the context of LHS.

[Lipase hypersecretion syndrome and bone lesions in acinar cell cancer of the pancreas. Report of one case]. / Síndrome de hipersecreción de lipasa y lesiones óseas en el cáncer de células acinares del páncreas.

Lipase hypersecretion syndrome (LHS) is a rare paraneoplastic syndrome, associated with acinar cell carcinoma of the pancreas (ACCP) in 10% to 15% of patients. Clinically, LHS manifests itself with the appearance of subcutaneous fibrocystic nodules, associated with trophic changes in the overlying skin, such as ulcers or fistulas that are difficult to manage, mainly affecting the lower extremities. Additionally, lipolysis near the joints and in the intraosseous adipose tissue can cause bilateral arthralgias, especially of the knees and ankles. We report a 57-year-old man, with a history of insulin resistance and allergic rhinitis, who presented in June 2019 with multiple subcutaneous nodules in the lower extremities, predominantly in both ankles, associated with arthralgia in that region. Additionally, a CT scan of the abdomen revealed a significant abdominal mass, measuring approximately 17 cm and in contact with the body and tail of the pancreas, pathologically compatible with an ACCP. Treatment with capecitabine was started with a favorable progression. The patient currently presents a small left lateral retro malleolar fistula, which, given the analyzes, studies and reviewed literature is concluded to be a lesion in the context of LHS.

Activation of the Ae4 (Slc4a9) cation-driven Cl-/HCO3- exchanger by the cAMP-dependent protein kinase in salivary gland acinar cells.

Ae4 transporters are critical for Cl- uptake across the basolateral membrane of acinar cells in the submandibular gland (SMG). Although required for fluid secretion, little is known about the physiological regulation of Ae4. To investigate whether Ae4 is regulated by the cAMP-dependent signaling pathway, we measured Cl-/HCO3- exchanger activity in SMG acinar cells from Ae2-/- mice, which only express Ae4, and found that the Ae4-mediated activity was increased in response to ß-adrenergic receptor stimulation. Moreover, pretreatment with H89, an inhibitor of the cAMP-activated kinase (PKA), prevented the stimulation of Ae4 exchangers. We then expressed Ae4 in CHO-K1 cells and found that the Ae4-mediated activity was increased when Ae4 is coexpressed with the catalytic subunit of PKA (PKAc), which is constitutively active. Ae4 sequence analysis showed two potential PKA phosphorylation serine residues located at the intracellular NH2-terminal domain according to a homology model of Ae4. NH2-terminal domain Ser residues were mutated to alanine (S173A and S273A, respectively), where the Cl-/HCO3- exchanger activity displayed by the mutant S173A was not activated by PKA. Conversely, S273A mutant kept the PKA dependency. Together, we conclude that Ae4 is stimulated by PKA in SMG acinar cells by a mechanism that probably depends on the phosphorylation of S173.NEW & NOTEWORTHY We found that Ae4 exchanger activity in secretory salivary gland acinar cells is increased upon ß-adrenergic receptor stimulation. The activation of Ae4 was prevented by H89, a nonselective PKA inhibitor. Protein sequence analysis revealed two residues (S173 and S273) that are potential targets of cAMP-dependent protein kinase (PKA). Experiments in CHO-K1 cells expressing S173A and S273A mutants showed that S173A, but not S273A, is not activated by PKA.

The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells.

Nek2 (NIMA-related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53-/- xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6's chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high-fat diet damages.

Imbalance of sexual steroids milieu and oxidative stress are often observed during aging and correlated to prostate disorders. Likewise, high-fat intake has been related to prostate damage and tumor development. Melatonin (MLT) is an antioxidant whose secretion decreases in elderly and is also suggested to protect the gland. This study evaluated the impact of a long-term high-fat diet during aging on prostate morphology and antioxidant system of rats and tested the effects of MLT supplementation under these conditions. Male rats were assigned into four groups: control, treated with MLT, high-fat diet and high-fat diet treated with MLT. The high-fat diet was provided from the 24th week of age, MLT from the 48th (100 µg/kg/day) and rats were euthanized at the 62nd week. The high-fat diet increased body weight, retroperitoneal fatness, glycaemia, and circulating estrogen levels. It aggravated the aging effects, leading to epithelial atrophy (∼32% reduction of epithelial height) and collagen fibers increase (83%). MLT alone did not alter biometric and physiological parameters, except for the prostate weight decrease, whereas it alleviated biometric as well as ameliorated acinar atrophy induced by high-lipid intake. Systemic oxidative stress increased, and prostatic glutathione peroxidase activity decreased fivefold with the high-fat diet despite the indole. Regardless of the diet, MLT triggered epithelial desquamation, reduced androgen receptor-positive cells, increased smooth muscle layer thickness (12%), decreased at least 50% corpora amylacea formation, and stimulated prostatic gluthatione-S-transferase activity. In conclusion, MLT partially recovered prostate damage induced by aging and the long-term high-fat diet and ameliorated degenerative prostate alterations.

Aberrant MUC1 accumulation in salivary glands of Sjögren's syndrome patients is reversed by TUDCA in vitro.

OBJECTIVES: Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. METHODS: Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-α or IFN-γ and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-κB subunit), TNF-α, IL-1ß, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. RESULTS: MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-α and IFN-γ, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. CONCLUSION: Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.

Lingual salivary gland hypertrophy and decreased acinar density in chagasic patients without megaesophagus.

Although the salivary glands present several functions, there are few studies evaluating these glands in Chagas disease (CD). This study aimed to compare the percentage of collagen, the presence of inflammation, the density of chimase and tryptase mast cells, the area and density of lingual salivary gland acini in autopsied individuals with and without (CD). We analyzed 400 autopsy reports performed in a tertiary public hospital from 1999 to 2015 and selected all the cases in which tongue fragments were collected (27 cases), 12 with chronic CD without megaesophagus (CH) and 15 without CD (non-chagasic - NC). The histological sections of the tongue were stained by Picrosirius red for collagen evaluation and Hematoxylin-eosin for morphometric evaluation of salivary gland acini and inflammation. Anti-chimase and anti-tryptase antibodies were used for the immunohistochemical evaluation of mast cells. The chagasic patients presented higher volume and lower density of salivary glands acini. There was no difference in the collagen percentage, inflammation and density of mast cell chymase and tryptase between the groups. Although we did not observe a significant difference between the groups regarding the collagen percentage, inflammatory process and mast cell density, our results suggest that even without megaesophagus, chagasic patients present hypertrophy of the lingual salivary glands and lower acinar density probably due to mechanisms independent of the esophagus-glandular stimulus.

Histopathological changes in parotid gland following submandibular gland failure: an experimental animal study / Alterações histopatológicas na glândula parótida após insuficiência da glândula submandibular: estudo experimental em animais

Abstract Introduction: Submandibular glands are exposed to many effects due to diseases and therapeutic interventions. A study evaluating the effect of submandibular gland dysfunction on the parotid gland has not been presented in the literature. Objective: The aim of this study was to evaluate the histopathological changes in the parotid gland following submandibular gland failure. Methods: Three groups of seven randomly selected female New Zealand rabbits weighing 2500-3000 g were studied. Unilateral and bilateral submandibular glands were removed in Groups 1 and 2, respectively. No procedure was performed in Group III, the control group. The parotid glands were removed 30 days later. Histological parameters were evaluated and graded between 0 (none) and 3 (severe). Differences between groups were compared using the Mann-Whitney U test. Results: Mean mucus accumulation in acinar cells was 2.57 ± 0.53 and 1.71 ± 0.75 in Groups 1 and 2, respectively (p < 0.05). This value was 0.57 ± 0.53 in Group 3, which was significantly lower than in Groups 1 and 2 (p < 0.05). Mean dilatation of the intercalated ducts' lumen was 1.28 ± 0.48 and 1.57 ± 0.53 in Groups 1 and 2, respectively (p > 0.05). This value was 0.28 ± 0.48 in Group 3, which was significantly lower than in Groups 1 and 2 (p < 0.05). Mean mucus accumulation in the intercalated ducts' lumen was 2.00 ± 0.81 and 1.00 ± 0.57 in Groups 2 and 3, respectively (p < 0.05). Conclusion: The findings of this study indicate that only 1 month after submandibular gland failure, the parotid glands exhibit significant changes.

Resumo Introdução: As glândulas submandibulares estão expostas a muitos efeitos causados por doenças e intervenções terapêuticas. Estudos que avaliam o efeito da disfunção da glândula submandibular na glândula parótida ainda não foram reportados na literatura. Objetivo: O objetivo deste estudo foi avaliar as alterações histopatológicas na glândula parótida após insuficiência da glândula submandibular. Método: Três grupos de sete coelhas fêmeas da raça Nova Zelândia, selecionadas aleatoriamente, pesando entre 2.500 e 3.000 gramas foram estudadas. As glândulas submandibulares unilaterais e bilaterais foram removidas nos Grupos 1 e 2, respectivamente. Nenhum procedimento foi realizado no Grupo III, o grupo controle. As glândulas parótidas foram removidas 30 dias depois. Os parâmetros histológicos foram avaliados e classificados entre 0 (nenhum) e 3 (grave). As diferenças entre os grupos foram comparadas usando o teste U de Mann-Whitney. Resultados: O acúmulo médio de muco nas células acinares foi de 2,57 ± 0,53 e 1,71 ± 0,75 nos Grupos 1 e 2, respectivamente (p < 0,05). Esse valor foi de 0,57 ± 0,53 no Grupo 3, significativamente menor do que nos Grupos 1 e 2 (p < 0,05). A dilatação média do lúmen dos dutos intercalados foi de 1,28 ± 0,48 e 1,57 ± 0,53 nos Grupos 1 e 2, respectivamente (p > 0,05). Esse valor foi de 0,28 ± 0,48 no Grupo 3, significativamente menor do que nos Grupos 1 e 2 (p < 0,05). O acúmulo médio de muco no lúmen dos dutos intercalados foi 2,00 ± 0,81 e 1,00 ± 0,57 nos Grupos 2 e 3, respectivamente (p < 0,05). Conclusão: Os achados deste estudo indicam que apenas um mês após a insuficiência da glândula submandibular as glândulas parótidas apresentam alterações significativas.

Measuring Autophagy in Pancreatitis.

Acute pancreatitis is one of the first pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion, and cell death are early cellular events in acute pancreatitis. Recent advances in understanding autophagy highlight its importance in pathological conditions. However, methods for monitoring autophagic activity during complex diseases, involving highly differentiated secretory cells, are complicated, and the results are sometimes misinterpreted. Here, we describe methods used to identify autophagic structures and to measure autophagic flux in cultured cell models and animal models of pancreatitis. We also briefly describe the pancreas specific autophagy mouse model that was useful to understand the actual role of autophagy in pancreatitis and to identify a novel selective autophagy pathway named zymophagy. Lastly, we describe the immunomagnetic isolation of autophagosomes and the detection of autophagy in pancreatic tissue samples derived from humans.

The exocrine pancreas is an extracardiac source of atrial natriuretic peptide.

Previous studies have shown that atrial natriuretic peptide (ANP) regulates exocrine pancreatic function in health and disease. As extracardiac sources of ANP have been identified and ANP-like immunoreactivity has been reported in the exocrine pancreas, in the present work we sought to establish whether ANP was produced in the rat exocrine pancreas and if conditions like fasting/feeding or acute pancreatitis were reflected on ANP expression. By using RT-PCR, immunoblotting, and immunofluorescence microscopy assays, it was found that both mRNA and protein ANP were present in the acinar cells of the exocrine pancreas. The amount of ANP in the pancreas was lower in than the atrium but similar to other tissues like the kidney and liver. Immunogold labeling electron microscopy studies revealed that ANP was localized in zymogen granules and the endoplasmic reticulum suggesting local synthesis and package into granules. ANP protein expression was significantly increased not only in fasting but also in acute pancreatitis, the latter probably related to impaired secretion. Natriuretic peptide receptor type C which mediates ANP biological effects in the exocrine pancreas was also present in acinar cells and its expression did not change with either fasting or acute pancreatitis. Present findings show that the exocrine pancreas is a relatively important extracardiac source of ANP and further support previous studies strongly suggesting the active role of the peptide in pancreatic physiology and pathophysiology.

Histopathological changes in parotid gland following submandibular gland failure: an experimental animal study.

INTRODUCTION: Submandibular glands are exposed to many effects due to diseases and therapeutic interventions. A study evaluating the effect of submandibular gland dysfunction on the parotid gland has not been presented in the literature. OBJECTIVE: The aim of this study was to evaluate the histopathological changes in the parotid gland following submandibular gland failure. METHODS: Three groups of seven randomly selected female New Zealand rabbits weighing 2500-3000g were studied. Unilateral and bilateral submandibular glands were removed in Groups 1 and 2, respectively. No procedure was performed in Group III, the control group. The parotid glands were removed 30 days later. Histological parameters were evaluated and graded between 0 (none) and 3 (severe). Differences between groups were compared using the Mann-Whitney U test. RESULTS: Mean mucus accumulation in acinar cells was 2.57±0.53 and 1.71±0.75 in Groups 1 and 2, respectively (p<0.05). This value was 0.57±0.53 in Group 3, which was significantly lower than in Groups 1 and 2 (p<0.05). Mean dilatation of the intercalated ducts' lumen was 1.28±0.48 and 1.57±0.53 in Groups 1 and 2, respectively (p>0.05). This value was 0.28±0.48 in Group 3, which was significantly lower than in Groups 1 and 2 (p<0.05). Mean mucus accumulation in the intercalated ducts' lumen was 2.00±0.81 and 1.00±0.57 in Groups 2 and 3, respectively (p<0.05). CONCLUSION: The findings of this study indicate that only 1 month after submandibular gland failure, the parotid glands exhibit significant changes.

Regeneration of Salivary Gland Defects of Diabetic Wistar Rats Post Human Dental Pulp Stem Cells Intraglandular Transplantation on Acinar Cell Vacuolization and Interleukin-10 Serum Level

Abstract Objective: To investigate the regeneration of rat's salivary gland diabetic defect after intraglandular transplantation of Human Dental Pulp Stem Cells (HDPSCs) on acinar cell vacuolization and Interleukin-10 (IL-10). Material and Methods: HDPSCs isolated from the dental pulp of first premolars #34. HDPSCs from the 3rd passage was characterized by immunocytochemistry of CD73, CD90, CD105 and CD45. Twenty-four male Wistar rats, 3-month-old, 250-300 grams induced with Streptozotocin 30 mg/kg body weight to create diabetes mellitus (DM) divided into 4 groups (n=6); positive control group on Day-7; positive control group on Day-14; treatment group Day-7 (DM+5.105HDPSCs); treatment group on Day-14. On Day-7 and Day-14, rats were sacrificed. Histopathological examination performed to analyze acinar cells vacuolization while Enzyme-linked Immunoabsorbent Assay to measure IL-10 serum level. Data obtained were analyzed statistically using multiple comparisons Bonferroni test, Kruskal Wallis, Shapiro-Wilk and Levene's test result Results: The highest acinar cell vacuolization found in control group Day 14 (0.239 ± 0.132), meanwhile the lowest acinar cell vacuolization found in treatment group Day 7 (0.019 ± 0.035) with significant difference (p=0.003). The highest IL-10 serum level found in treatment group Day 14 (175.583 ± 120.075) with significant difference (p=0.001) Conclusion: Transplantation of HDPSC was able to regenerate submandibular salivary gland defects in diabetic rats by decreasing acinar cell vacuolization and slightly increase IL-10 serum level.

Effect of low radiation dose on the expression and location of aquaporins in rat submandibular gland.

Head and neck cancers are common in several regions of the world and the treatment usually includes radiotherapy. This treatment can generate adverse effects to the salivary flow, with a relationship between the dose and the damage caused. Salivary gland cells are highly permeable to water and therefore, they express aquaporins (AQPs). This study analyzed changes in the expression and location of these proteins and identified morphological changes induced by low radiation in rat submandibular gland. Female rats were divided into control and irradiated groups. Immunohistochemistry analysis allowed confirming the presence of AQP1 in the blood vessel endothelium. Intense and steady labelling granules were also observed in the cytoplasm of submandibular gland ductal cells. In addition, there was AQP5 positive labelling in ductal cells delimiting the lumen of intercalated duct, in the cytoplasm and membrane of acinar cells. Finally, the decrease of AQP labelling in irradiated animal glands validated their radiosensitivity. Thus, the decrease in AQP1 protein levels in the endothelium and AQP5 in gland ductal cells of irradiated animals may have hindered the removal of water from the lumen of ductal cells, inducing a delay in water absorption and triggering a slight lumen increase.

Carcinoma de células acinares de glándula lacrimal metastásico en columna torácica. Reporte de un caso y revisión de la literatura / Acinar cell carcinoma of lacrimal gland metastatic a thoracic spine. Case report and literature review

Resumen El carcinoma de células acinares es una neoplasia poco frecuente que se presenta principalmente en las glándulas salivales. Presentamos el caso de un paciente femenino de 48 años con dolor, paresia palpebral derecha y aumento de volumen. Biopsia que confirma diagnóstico, manejada con exenteración orbitaria derecha más RT. Durante seguimiento seis años después se presenta dolor columna dorsal, RMN con lesión osteoblástica en T2 biopsia con metástasis de carcinoma de células acinares. Debido a su baja incidencia el comportamiento del carcinoma de células acinares de la glán dula lacrimal es incierto, no hay reportes en la literatura de lesiones metastásicas únicas en columna.

Abstract Acinar cell carcinoma is a rare neoplasm occurs primarily in the salivary glands. We report the case of a female patient of 48 years with pain, right palpebral paresis, and increased volume. Biopsy confirmed diagnosis, handled right exenteration more RT. During follow-up six years after dorsal spine pain, MRI with T2 lesion biopsy osteoblastic metastatic carcinoma of acinar cells. Because of its low incidence behavior acinar cell carcinoma of the lacrimal gland is uncertain, there are no reports in the literature of metastatic lesions unique column.

Paracrine Secretion of Transforming Growth Factor ß by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues.

OBJECTIVE: We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. METHODS: We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. RESULTS: A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor ß (TGF-ß) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-ß to induce ADM in human acinar cells. In addition, we found that TGF-ß cannot induce ADM of murine acinar cells. CONCLUSIONS: Ductal cells are the major source of TGF-ß that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.

The expression of water channel proteins during human salivary gland development: a topographic study of aquaporins 1, 3 and 5.

Some members of aquaporin family (AQP) plays crucial functions in salivary synthesis and secretion. These proteins expression has already been reported during salivary gland formation, however no previous studies in human developing glands have been performed. We evaluated AQP1, 3 and 5 expression through the stages of human salivary gland morphogenesis and discuss the possible role of AQP for glandular maturation. Human salivary glands derived from foetuses aged between 14 and 25 weeks were submitted to immunohistochemistry. At the bud stage, membrane expression of AQP1, 3 and 5 were observed within the epithelial bud cells presenting a similar apicolateral pattern, also found at the pseudoglandular stage, present within the terminal portions of future acini, while AQP5 was also particularly strong at the apical membrane of pre-acinar and pre-ductal cells. AQP5 was co-localised with Cytokeratin 7. Similar AQP1, 3 and 5 expression were observed at the following canalicular stage, where distinct and strongly luminal and acinar AQP5 expression is present. During the final terminal bud stage, AQP1 was only identified in serous acini, myoepithelial and endothelial cells, while differentiated mucous acinar cells and ducts were negative. AQP3 was detected at apicolateral membranes of both mucous and serous acini. AQP5 also showed a diffuse expression in mucous and serous acini, in addition to strong apical membrane expression within lumen of intercalated ductal cells. This topographic analysis of AQP1, 3 and 5 revealed differences in the expression pattern throughout salivary gland developmental stages, suggesting different roles for each protein in human glandular maturation.

Salivary epidermal growth factor concentrations in patients with Sjögren syndrome and laryngopharyngeal reflux.

Sjögren syndrome was chosen as a clinical model to study acinar salivary deficiencies in the development of laryngopharyngeal reflux (LPR). The objective of this prospective cohort study was to compare salivary epidermal growth factor (EGF) concentrations of patients with Sjögren syndrome with and without LPR and gastroesophageal reflux disease (GERD) with normal controls. LPR was diagnosed with positive scores on the Reflux Symptom Index and Reflux and Reflux Finding Score, corroborated by esophagogastroduodenoscopy and/or 24-hour pH-metry. Salivary EGF concentrations of both unstimulated and mechanically stimulated saliva were established using enzyme-linked immunosorbent assay, and the significance level was set at 95%. Twenty-one patients and 19 controls were studied. All patients had LPR and 60% also had GERD. The mean salivary EGF concentration of unstimulated and stimulated saliva in the control group was 1,751.37 pg/ml and 544.76 pg/ml, respectively. Unstimulated and stimulated salivary EGF concentrations in the study group were 2,534.65 pg/ml and 920.69 pg/ml, respectively. These differences were not statistically significant. Body mass index, presence of erosive esophagitis, or severity of hyposalivation did not significantly influence salivary EGF concentrations. LPR and GERD are highly prevalent in patients with Sjögren syndrome. Unlike previous studies in which significant EGF deficiencies were found in patients with reflux laryngitis and GERD, patients with Sjögren syndrome seem to have reflux caused by a decrease in clearance capacity and not in specific salivary components.