ABSTRACT
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.
Subject(s)
COVID-19 , ErbB Receptors , SARS-CoV-2 , Submandibular Gland , Xerostomia , COVID-19/pathology , COVID-19/virology , COVID-19/metabolism , Animals , Submandibular Gland/virology , Submandibular Gland/pathology , Submandibular Gland/metabolism , SARS-CoV-2/physiology , Mice , Xerostomia/etiology , Xerostomia/pathology , Xerostomia/virology , Xerostomia/metabolism , ErbB Receptors/metabolism , Humans , Angiotensin-Converting Enzyme 2/metabolism , Mucin-5B/metabolism , Acinar Cells/pathology , Acinar Cells/metabolism , Acinar Cells/virology , Interleukin-1beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Disease Models, AnimalABSTRACT
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.
Subject(s)
Humans , Male , Middle Aged , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnostic imaging , Skin Neoplasms , Carcinoma, Acinar Cell/complications , Carcinoma, Acinar Cell/pathology , Pancreas/pathology , Acinar Cells/pathology , Abdomen/pathology , LipaseABSTRACT
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.
Subject(s)
Carcinoma, Acinar Cell , Pancreatic Neoplasms , Skin Neoplasms , Male , Humans , Middle Aged , Carcinoma, Acinar Cell/complications , Carcinoma, Acinar Cell/pathology , Acinar Cells/pathology , Pancreas/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Abdomen/pathology , Lipase , Pancreatic NeoplasmsABSTRACT
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.
Subject(s)
Centrosome/metabolism , Epithelial-Mesenchymal Transition , NIMA-Related Kinases/metabolism , Triple Negative Breast Neoplasms/enzymology , Acinar Cells/pathology , Aneuploidy , Animals , Carcinogenesis , Cell Line, Tumor , Cell Movement , Chromosomal Instability , Epithelial Cells/pathology , Female , Humans , Mice , Neoplasm Invasiveness , Snail Family Transcription Factors/metabolism , Survival Analysis , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
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 (â¼32% 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.
Subject(s)
Melatonin/pharmacology , Prostate/pathology , Acinar Cells/drug effects , Acinar Cells/pathology , Adiposity/drug effects , Animals , Collagen/metabolism , Diet, High-Fat , Epithelium/drug effects , Epithelium/pathology , Male , Oxidative Stress/drug effects , Proliferating Cell Nuclear Antigen/metabolism , Prostate/drug effects , Rats , Receptors, Androgen/metabolism , Retroperitoneal Space/pathologyABSTRACT
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.
Subject(s)
Acinar Cells/pathology , Chagas Disease/pathology , Salivary Glands/pathology , Tongue/pathology , Aged , Chronic Disease , Female , Humans , Hypertrophy , Immunohistochemistry , MaleABSTRACT
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.
Subject(s)
Animals , Female , Rats , Parotid Gland/pathology , Submandibular Gland/surgery , Parotid Gland/surgery , Models, Animal , Acinar Cells/pathology , MucusABSTRACT
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.
Subject(s)
Parotid Gland/pathology , Submandibular Gland/surgery , Acinar Cells/pathology , Animals , Female , Models, Animal , Mucus , Parotid Gland/surgery , RabbitsABSTRACT
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.
Subject(s)
Acinar Cells/metabolism , Aquaporin 1/biosynthesis , Aquaporin 5/biosynthesis , Gamma Rays/adverse effects , Gene Expression Regulation/radiation effects , Submandibular Gland/metabolism , Acinar Cells/pathology , Animals , Dose-Response Relationship, Radiation , Female , Rats , Rats, Wistar , Submandibular Gland/pathologyABSTRACT
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.
Subject(s)
Acinar Cells/metabolism , Pancreas, Exocrine/metabolism , Pancreatic Ducts/metabolism , Transforming Growth Factor beta/metabolism , Acinar Cells/pathology , Animals , Cells, Cultured , Flow Cytometry , Gene Expression , Humans , Metaplasia , Mice , Pancreatic Ducts/pathology , Paracrine Communication , Reverse Transcriptase Polymerase Chain Reaction , Tissue Culture Techniques , Transforming Growth Factor beta/geneticsABSTRACT
ABSTRACT Background Prostate-specific antigen densities have limited success in diagnosing prostate cancer. We emphasise the importance of the peripheral zone when considered with its cellular constituents, the “prostatocrit”. Objective Using zonal volumes and asymmetry of glandular acini, we generate a peripheral zone acinar volume and density. With the ratio to the whole gland, we can better predict high grade and all grade cancer. We can model the gland into its acinar and stromal elements. This new “prostatocrit” model could offer more accurate nomograms for biopsy. Materials and Methods 674 patients underwent TRUS and biopsy. Whole gland and zonal volumes were recorded. We compared ratio and acinar volumes when added to a “clinic” model using traditional PSA density. Univariate logistic regression was used to find significant predictors for all and high grade cancer. Backwards multiple logistic regression was used to generate ROC curves comparing the new model to conventional density and PSA alone. Outcome and results Prediction of all grades of prostate cancer: significant variables revealed four significant “prostatocrit” parameters: log peripheral zone acinar density; peripheral zone acinar volume/whole gland acinar volume; peripheral zone acinar density/whole gland volume; peripheral zone acinar density. Acinar model (AUC 0.774), clinic model (AUC 0.745) (P=0.0105). Prediction of high grade prostate cancer: peripheral zone acinar density (“prostatocrit”) was the only significant density predictor. Acinar model (AUC 0.811), clinic model (AUC 0.769) (P=0.0005). Conclusion There is renewed use for ratio and “prostatocrit” density of the peripheral zone in predicting cancer. This outperforms all traditional density measurements.
Subject(s)
Humans , Male , Aged , Prostate/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , Acinar Cells/pathology , Reference Standards , Biopsy , Logistic Models , Predictive Value of Tests , Reproducibility of Results , ROC Curve , Stromal Cells , Neoplasm Grading , Middle AgedABSTRACT
BACKGROUND: Prostate-specific antigen densities have limited success in diagnosing prostate cancer. We emphasise the importance of the peripheral zone when considered with its cellular constituents, the "prostatocrit". OBJECTIVE: Using zonal volumes and asymmetry of glandular acini, we generate a peripheral zone acinar volume and density. With the ratio to the whole gland, we can better predict high grade and all grade cancer. We can model the gland into its acinar and stromal elements. This new "prostatocrit" model could offer more accurate nomograms for biopsy. MATERIALS AND METHODS: 674 patients underwent TRUS and biopsy. Whole gland and zonal volumes were recorded. We compared ratio and acinar volumes when added to a "clinic" model using traditional PSA density. Univariate logistic regression was used to find significant predictors for all and high grade cancer. Backwards multiple logistic regression was used to generate ROC curves comparing the new model to conventional density and PSA alone. OUTCOME AND RESULTS: Prediction of all grades of prostate cancer: significant variables revealed four significant "prostatocrit" parameters: log peripheral zone acinar density; peripheral zone acinar volume/whole gland acinar volume; peripheral zone acinar density/whole gland volume; peripheral zone acinar density. Acinar model (AUC 0.774), clinic model (AUC 0.745) (P=0.0105). Prediction of high grade prostate cancer: peripheral zone acinar density ("prostatocrit") was the only significant density predictor. Acinar model (AUC 0.811), clinic model (AUC 0.769) (P=0.0005). CONCLUSION: There is renewed use for ratio and "prostatocrit" density of the peripheral zone in predicting cancer. This outperforms all traditional density measurements.
Subject(s)
Acinar Cells/pathology , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Aged , Biopsy , Humans , Logistic Models , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , ROC Curve , Reference Standards , Reproducibility of Results , Stromal CellsABSTRACT
The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC.
Subject(s)
Cyprinodontiformes/growth & development , Disorders of Sex Development/etiology , Ethinyl Estradiol/toxicity , Gonads/drug effects , Liver/drug effects , Acinar Cells/drug effects , Acinar Cells/pathology , Animals , Cyprinodontiformes/physiology , Disorders of Sex Development/pathology , Disorders of Sex Development/veterinary , Fatty Liver/etiology , Fatty Liver/veterinary , Female , Gonads/growth & development , Gonads/pathology , Liver/metabolism , Liver/pathology , Male , Necrosis , Oocytes/drug effects , Oocytes/growth & development , Oocytes/pathology , Testis/drug effects , Testis/growth & development , Testis/pathologyABSTRACT
Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer.
Subject(s)
Acinar Cells/pathology , Islets of Langerhans/pathology , Karwinskia/toxicity , Pancreatitis, Acute Necrotizing/pathology , Animals , Disease Models, Animal , Immunohistochemistry , Rats , Rats, WistarABSTRACT
UNLABELLED: Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. OBJECTIVE: The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. MATERIAL AND METHODS: 186 cadavers' glands were allocated to age groups: I (0-30 years); II (31-60), and III (61-90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman's correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). RESULTS: There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. CONCLUSION: Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.
Subject(s)
Acinar Cells/pathology , Autolysis/pathology , Sublingual Gland/pathology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Autopsy , Cadaver , Child , Child, Preschool , Female , Humans , Infant , Male , Microscopy, Electron, Transmission , Middle Aged , Mucous Membrane/pathology , Sex Factors , Statistics, Nonparametric , Time Factors , Young AdultABSTRACT
Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05).Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Acinar Cells/pathology , Autolysis/pathology , Sublingual Gland/pathology , Age Factors , Autopsy , Cadaver , Microscopy, Electron, Transmission , Mucous Membrane/pathology , Sex Factors , Statistics, Nonparametric , Time FactorsABSTRACT
AIM: To compare the prevalence of diverse histopathologic features among patients with Sjögren's syndrome (SS) and controls, and to evaluate their relationship with age, a focus score (FS) ≥ 1 and some clinical and serological SS features. METHODS: A blinded pathologist examined 63 SS and 11 control minor salivary gland biopsies. Focal lymphocytic sialadenitis (FLS) was defined as a focus score (FS) ≥ 1. We also evaluated lymphoepithelial lesions, germinal centers (GCs), epithelial metaplasia, dilatation and hyperplasia in the main secretory duct, perivascular cell infiltrate, adipose infiltration, acinar atrophy, interstitial fibrosis and lymphocytes/plasma cells remote from the FLS. We registered demographics, anti-Ro/La status and clinical features. We used Kendall's tau coefficients and logistic regression analysis. RESULTS: Sjögren's syndrome patients had a higher frequency of FS ≥ 1 (92% vs. 27%), acinar atrophy (78% vs. 18%), lymphocytes and plasma cells external to the FSL (92% vs. 64%) and stromal fibrosis (68% vs. 36%). A FS ≥ 1 correlated with the presence of GCs and acinar atrophy; whereas age correlated with duct dilation, duct epithelial hyperplasia, adipose infiltration and fibrosis. SS patients with hepatic involvement exhibited more frequent duct dilatation. After adjusting by age, anti-Ro/SSA (odds ratio [OR] 30.8, 95% CI 2.2-423.5, P = 0.01), a FS ≥ 1 (OR 54.3, 95% CI 4.8-612, P = 0.001) and fibrosis (OR 15.2, 95% CI 1.2-186.2, P = 0.03) were associated with SS. CONCLUSION: Other histologic findings coexist with FLS, but only GC formation and acinar atrophy correlated with a FS ≥ 1. Age is mostly correlated with the remaining histological features. However, the clinical relevance of these findings is unknown.
Subject(s)
Sialadenitis/pathology , Sjogren's Syndrome/pathology , Acinar Cells/pathology , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Salivary Ducts/pathologyABSTRACT
Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). Results: Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements. .
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Mouth, Edentulous/pathology , Sublingual Gland/anatomy & histology , Acinar Cells/pathology , Adipose Tissue/anatomy & histology , Aging/physiology , Cadaver , Hypertrophy/pathology , Mouth Floor , Reference Values , Statistics, Nonparametric , Stromal CellsABSTRACT
Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.
Subject(s)
Acinar Cells/pathology , Breast Neoplasms/pathology , Collagen/metabolism , Cyclooxygenase 2/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Monocyte-Macrophage Precursor Cells/enzymology , Acinar Cells/metabolism , Breast Neoplasms/genetics , Cell Communication/genetics , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Coculture Techniques , Dinoprostone/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Extracellular Matrix/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Models, Biological , Monocyte-Macrophage Precursor Cells/pathology , Neoplasm Invasiveness , Phenotype , Proteolysis , Solubility , Up-RegulationABSTRACT
UNLABELLED: Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. OBJECTIVE: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. MATERIAL AND METHODS: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). RESULTS: Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.