Hygroscopic nature of betel quid: a cause for acinar cell degeneration and xerostomia

ABSTRACT LKB1 is a key regulator of energy homeostasis through the activation of AMP-activated protein kinase (AMPK) and is functionally linked to vascular development, cell polarity, and tumor suppression. In humans, germ line LKB1 loss-of-function mutations cause Peutz-Jeghers syndrome (PJS), which is characterized by a predisposition to gastrointestinal neoplasms marked by a high risk of pancreatic cancer. To explore the developmental and physiological functions of Lkb1 in vivo, we examined the impact of conditional Lkb1 deletion in the pancreatic epithelium of the mouse. The Lkb1-deficient pancreas, although grossly normal at birth, demonstrates a defective acinar cell polarity, an abnormal cytoskeletal organization, a loss of tight junctions, and an inactivation of the AMPK/MARK/SAD family kinases. Rapid and progressive postnatal acinar cell degeneration and acinar-to-ductal metaplasia occur, culminating in marked pancreatic insufficiency and the development of pancreatic serous cystadenomas, a tumor type associated with PJS. Lkb1 deficiency also impacts the pancreas endocrine compartment, characterized by smaller and scattered islets and transient alterations in glucose control. These genetic studies provide in vivo evidence of a key role for LKB1 in the establishment of epithelial cell polarity that is vital for pancreatic acinar cell function and viability and for the suppression of neoplasia.

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The Histopathologic Effects of l-Carnitine in a Sodium Taurocholate–Induced Severe Pancreatitis Model

International Surgery ◽

10.9738/intsurg-d-16-00058.1 ◽

2016 ◽

Vol 101 (5-6) ◽

pp. 241-248 ◽

Cited By ~ 2

Author(s):

Murat Karakahya ◽

Mehmet Gül ◽

Sevil Işık ◽

Cemalettin Aydın ◽

Birgül Yiğitcan ◽

...

Keyword(s):

Acinar Cell ◽

Cell Injury ◽

Sodium Taurocholate ◽

Active Role ◽

Male Rats ◽

Sprague Dawley ◽

Cell Degeneration ◽

Severe Pancreatitis ◽

Pancreatic Damage ◽

Histopathologic Findings

This study aims to evaluate the histopathologic effects of l-carnitine (LC) in an experimental severe pancreatitis (SP) model induced with sodium taurocholate. LC is an amino acid–like molecule that plays an active role in transporting fatty acids and producing acetyl CoA in mitochondrial matrix for β-oxidation to provide energy that is needed for metabolism. It has ameliorative effects on cell injury, as has been demonstrated in many studies. The present study focuses on evaluating the histopathologic effects of LC in an experimental SP model. A total of 32 Sprague-Dawley male rats were divided into 4 groups in a randomized fashion: control (C) group, l-carnitine (LC) group, pancreatitis (P) group, and pancreatitis and l-carnitine (P + LC) group. Pancreatitis was induced by a retrograde pancreatic duct injection of 4% sodium taurocholate, and LC was administered 200 mg/kg/d in the treatment group. Rats were euthanized with cardiac puncture under anesthesia at the 48th hour of the experiment for biochemical and histopathologic examination. In the P + LC group, the histopathologic findings of the pancreatitis were markedly reduced. Acinar cell degeneration was rarely seen. Interlobular and intralobular inflammation and edema was generally mild. The pancreatic damage score of the P + LC group was significantly lower than that of the P group (P < 0.05). This study revealed that LC has a significant histopathologic protective effect on acinar cell degeneration in a sodium taurocholate–induced SP model in rats.

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Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1519384112 ◽

2015 ◽

Vol 112 (45) ◽

pp. E6166-E6174 ◽

Cited By ~ 96

Author(s):

Laura Antonucci ◽

Johan B. Fagman ◽

Ju Youn Kim ◽

Jelena Todoric ◽

Ilya Gukovsky ◽

...

Keyword(s):

Er Stress ◽

Acinar Cell ◽

Molecular Mechanisms ◽

Cell Function ◽

Pancreatic Neoplasm ◽

Acinar Cells ◽

Pancreatic Acinar Cells ◽

Ductal Adenocarcinoma ◽

Autophagic Flux ◽

Cell Degeneration

Pancreatic acinar cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The cellular and molecular mechanisms that maintain acinar cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7Δpan mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial cells. Atg7Δpan mice exhibit severe acinar cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7Δpan mice also exhibit spontaneous activation of regenerative mechanisms that initiate acinar-to-ductal metaplasia (ADM), a process that replaces damaged acinar cells with duct-like structures.

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A complex network of “snake-like tubules” revealed by the NADPase cytochemical reaction in the acinar cell of pancreas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113214 ◽

1984 ◽

Vol 42 ◽

pp. 666-667

Author(s):

A.R. Beaudoin ◽

G. Grondin ◽

A. Lord ◽

M. Pelletier

Keyword(s):

Acinar Cell ◽

Lead Acetate ◽

Ultrastructural Localization ◽

Sodium Acetate Buffer ◽

Zymogen Granules ◽

Sprague Dawley ◽

Dense Bodies ◽

Sprague Dawley Rats ◽

Cytochemical Reaction ◽

Cellular Organelles

We have recently described the ultrastructural localization of NADPase activity in the exocrine pancreas of rat. The enzyme was found in the intermediate saccules of the Golgi apparatus, in dense bodies and lysosomes but was absent from zymogen granules. A very intense reaction was noticed in a peculiar structure which was termed “Snake-Like Tubule” (SLT). The purposes of the present study were firstly to delineate SLT distribution in the acinar cell and secondly to define any possible relationship or association with other cellular organelles.NADPase cytochemical reaction was performed on the pancreas of adult Sprague Dawley rats. Small lobules were excised and fixed for 50 min, at 4°C, in 2% glutaraldehyde buffered with 0.1M cacodylate at pH 7.2. Lobules were rinsed several times with the same buffer containing 570 sucrose and cut with a Mcllwayn tissue chopper. Sections were washed several times with buffer and incubated for 2 hr at 37°C in the following medium: 4mM NADPH; 40mM sodium acetate buffer, pH 5.0; 4mM lead acetate and 5% sucrose.

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Betel Quid Dependence Instrument

PsycTESTS Dataset ◽

10.1037/t71734-000 ◽

2019 ◽

Author(s):

Ming-Hsui Tsai ◽

Tsai-Chung Li ◽

Chia-Ing Li ◽

Ellen R. Gritz ◽

Cho Lam ◽

...

Keyword(s):

Betel Quid

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Histopathology of pancreatic acinar cell metaplasia in Barrett's esophagus

Zeitschrift für Gastroenterologie ◽

10.1055/s-2006-943512 ◽

2006 ◽

Vol 44 (05) ◽

Author(s):

L Tiszlavicz ◽

I Németh ◽

A Rosztóczy ◽

F Izbéki ◽

Z F. Kiss ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Acinar Cell ◽

Barrett's Esophagus ◽

Pancreatic Acinar Cell

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Role of Clinical Palpation in Evaluation of Cervical Lymph Node in Oral Squamous Cell Carcinoma

Update Dental College Journal ◽

10.3329/updcj.v1i2.13978 ◽

2013 ◽

Vol 1 (2) ◽

pp. 02-06

Author(s):

SM Anwar Sadat ◽

Sufia Nasrin Rita ◽

Shoma Banik ◽

Md Nazmul Hasan Khandker ◽

Md Mahfuz Hossain ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Oral Squamous Cell Carcinoma ◽

Lymph Nodes ◽

Cell Carcinoma ◽

Squamous Cell ◽

Predictive Value ◽

Cervical Lymph Node ◽

Betel Quid ◽

Cervical Lymph Nodes

A cross sectional study of 29 cases of oral squamous cell carcinoma with or without cervical lymph node metastasis was done among Bangladeshi patients from January 2006 to December 2007. Majority of the study subjects (34.5%) belonged to the age group of 40-49 years. 58.6% of the study subjects were male, while remaining 41.4% of them were female. 51.7% of the lesions were located in the alveolar ridge where the other common sites were buccal mucosa (27.6%) and retro molar area (13.8%). Half of the study subjects (51.7%) were habituated to betel quid chewing followed by 37.9% and 10.3% were habituated to smoking and betel quid-smoking respectively. Grade I lesions was most prevalent (75.9%) in the study subjects. Majority of cases presented with Stage IV lesions (55.2%). The sensitivity, specificity, positive predictive value, negative predictive value & accuracy of clinical palpation method for determining metastatic cervical lymph nodes were 93.33%, 64.29%, 73.68%, 90% and 79.3% respectively. Careful and repeated clinical palpation plays important role in evaluation of cervical lymph nodes though several modern techniques may help additionally in the management of oral cancer.DOI: http://dx.doi.org/10.3329/updcj.v1i2.13978 Update Dent. Coll. j. 2011: 1(2): 02-06

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