Interlobular Ducts Research Articles

Allergy-Related Sialodochitis: A Preliminary Cohort Study.

To explore the clinically feasible diagnosis criteria and treatment outcomes of allergy-related sialodochitis (ARS). Prospective Cohort Study. Ninety-six consecutive patients were enrolled by the following criteria: 1) recurrent swelling of ≥2 large salivary glands that lasted for ≥3 months; 2) with mucus plug exudations; 3) with atopic diseases; 4) ductal stenosis and/or ectasia. Sixty-four patients with elevation of peripheral blood eosinophil (PBE) and/or serum IgE level comprised group A (highly-suspected ARS group), while the remaining 32 comprised group B (patients without confirmed evidence of ARS). These patients were treated with interventional endoscopy. A chronic obstructive sialadenitis symptom (COSS) questionnaire was used to quantify the treatment outcomes. In group A, Serum IgE was elevated in 84.4% of patients and PBE was elevated in 34.4% of patients. Percentage of submandibular gland involvement was higher in group A than group B (48.4% vs. 18.8%). On sialograms, the snowflake changes of branch ducts were seen in higher percentage of group A compared with group B (59% vs. 35% for parotid glands, 27% vs. 8% for submandibular glands, respectively). Mucus plug smears showed abundant eosinophils in 14 group A patients. Biopsy of five group A patients revealed significant eosinophil infiltration around the main and interlobular ducts. During follow-up, the COSS scores were significantly decreased in both groups, and group B was improved better than group A. PBE and serum IgE are important diagnostic indexes of ARS. Mucus plug smear or histopathology verifies the diagnosis. Interventional endoscopy is helpful for ARS cases. 3 Laryngoscope, 131:2030-2035, 2021.

Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells

BackgroundStem cells from human exfoliated deciduous teeth (SHED) have been reported to show the in vivo and in vitro hepatic differentiation, SHED-Heps; however, the cholangiogenic potency of SHED-Heps remains unclear. Here, we hypothesized that SHED-Heps contribute to the regeneration of intrahepatic bile duct system in chronic fibrotic liver.MethodsSHED were induced into SHED-Heps under cytokine stimulation. SHED-Heps were intrasplenically transplanted into chronically CCl4-treated liver fibrosis model mice, followed by the analysis of donor integration and hepatobiliary metabolism in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile duct system in the recipient liver. Furthermore, SHED-Heps were induced under the stimulation of tumor necrosis factor alpha (TNFA).ResultsThe intrasplenic transplantation of SHED-Heps into CCl4-treated mice showed that donor SHED-Heps behaved as human hepatocyte paraffin 1- and human albumin-expressing hepatocyte-like cells in situ and ameliorated CCl4-induced liver fibrosis. Of interest, the integrated SHED-Heps not only expressed biliary canaliculi ATP-binding cassette transporters including ABCB1, ABCB11, and ABCC2, but also recruited human keratin 19- (KRT19-) and KRT17-positive cells, which are considered donor-derived cholangiocytes, regenerating the intrahepatic bile duct system in the recipient liver. Furthermore, the stimulation of TNFA induced SHED-Heps into KRT7- and SRY-box 9-positive cells.ConclusionsCollectively, our findings demonstrate that infused SHED-Heps showed cholangiogenic ability under the stimulation of TNFA in CCl4-damaged livers, resulting in the regeneration of biliary canaliculi and interlobular bile ducts in chronic fibrotic liver. Thus, the present findings suggest that SHED-Heps may be a novel source for the treatment of cholangiopathy.

Giant Hepatic Regenerative Nodule in a 17-year-old Woman with Alagille Syndrome: A Case Report

Author(s): Majumdar, Shamaita; Iskander, Paul; Luhar, Aarti | Abstract: Alagille Syndrome is a multisystem genetic disorder characterized by paucity of interlobular bile ducts, which can lead to early cirrhosis and increase the risk of developing focal liver lesions including hepatocellular carcinoma. As a result, routine imaging surveillance is often performed in these patients.nnHowever, it can be challenging to distinguishing incidentally found benign liver tumors from their malignant counterparts in this subset of patients. Here we present the case of a giant regenerative hepatic nodule in a 17-year-old female with Alagille syndrome, and the associated imaging characteristics that favored a benign diagnosis, with benign pathology confirmed by image-guided core needle biopsy.n

Vanishing bile duct syndrome in pediatric population: An updated case-based review

Vanishing bile duct syndrome (VBDS) is a rare and rapidly progressing condition where there is massive destruction or loss of the bile duct. The etiology of VBDS includes developmental abnormalities, immune-mediated, infectious disorders, drug-induced, neoplastic, and ischemic disorders. Certain drugs that are responsible for the development of this disease are non-steroidal anti-inflammatory drugs, sex steroids, antidepressants, immunomodulators, and antibiotics. The exact mechanism behind the progression of this condition is not established. The clinical presentation ranges from the presence of dark urine, discolored stools, pruritus, maculopapular rashes, jaundice, and liver failure in extreme cases. A confirmatory test for the diagnosis of VBDS is the presence of ductopenia, which is a 50% reduction of the interlobular bile duct in liver biopsy. Currently, treatment is to remove the offending agent and provide supportive care with drugs like Ursodeoxycholic acid, corticosteroids, and immunosuppressants. Prognosis varies from hepatic failure to liver transplantation and it may also result in death. This case-based review briefs the seven documented pediatric cases of acute drug-related VBDS. Based on these articles, different treatment options were analyzed to provide a better prognosis for patients who are suffering from VBDS.

Small salivary glands in the paratonsillar space in children

Was to study the changes in the small salivary glands in chronic tonsillitis and paratonsillar abscess in children. A histological examination of the palatine tonsils of 22 children aged 5 to 14 years old who had a paratonsillar abscess and 18 children suffering from chronic tonsillitis was carried out. Fragments of small salivary glands, located both superficially, in the mucous membrane between the stratified squamous non-keratinizing epithelium and the lymphoid tissue of the palatine tonsils, and between the muscles of the amygdala were found in 42 of the 80 (52.5%) tonsils studied. Along with the unchanged glandular structure, 26 (61.9%) samples revealed areas of destruction foci in small salivary glands with signs of inflammatory and compensatory regenerative activity. The presence of separate interlobular ducts of the salivary glands with pronounced periductal lymph - macrophage infiltration was noted. The subepithelial lymph-macrophage infiltrates found in the lamina propria are associated with the exit of the excretory ducts of the salivary glands to the surface of the mucous membrane. Many thin-walled veins are surrounded by perivascular lymphocellular infiltrates. The inflammatory and post-inflammatory changes in the small salivary glands revealed by us in children with chronic tonsillitis do not exclude their participation in the pathogenesis of paratonsillitis. At the same time, inflammation in the salivary gland can be both primary, as a result of its infection with live microorganisms from the tissues of the tonsil, and secondary, due to the compression of the excretory ducts by the edematous tissue of the tonsil in acute tonsillitis.

Macroscopical Anatomy and Radiographic Study of the Non-Lactating Udder of Adult Local Iraqi Cow (Bos taurus)

The purpose of this study was to describe some anatomical and radiological features of the non-lactating udder of adult local Iraqi cow. Eight udder of local breed cow clinically appeared healthy and aged between 2-5 years were obtained from a local slaughterhouse located at Baghdad province. Five udders were used for anatomical study and the rest 3 udders were used for the radiological study. The study primed to describe the macroscopic anatomy of the udder and investigate the udder’s normal blood supply using red-colored latex. The mammography method was to describe the duct system of the glandular tissue of the mammary gland which was performed using the iodine compound and barium sulphate as contrast media. The results showed that the udder was located in the inguinal region and covered by pigmented skin with fine hair and composed of four quarters. Each quarter has one teat which was long, cylindrical in shape, opened with one orifice; and internally has longitudinal folds in its mucous membrane. The blood supply of udder by the external pudendal arteries (left and right) branched into cranial and caudal mammary ones. The radiological study showed that the glandular tissue of udder was composed of complex ducal system which included the teat canal (long narrow), teat sinus (spindle-shaped cavity), lactiferous sinus (large round structure), lactiferous ducts, cistern ducts, interlobular duct, intralobular duct and alveoli (round sac like).In conclusion, this study is considered as an important contribution of describing the anatomical features, main blood supply and a pathway of the intraglandular duct system of the non-lactating udder in local cow breed which is necessary for surgical operations in several cases of the udder.

Histomorphological and Histochemical Studies on Proventriculus in Guinea Fowl (Numida meleagris)

Background: The proventriculus, component of digestive system of bird secretes hydrochloric acid and pepsinogen which helps the churning of food material that takes place in ventriculus. Pepsinogen produces pepsin and it smashes the peptide bonds of amino acid of food material. Methods: The twelve proventriculus samples of Guinea fowl birds were fixed in 10% neutral buffered formalin and Bouin’s fluid for histological procedure while chilled acetone and chilled ethanol were used as the fixatives for histochemical studies. The fresh unfixed samples were used on cryostat for studies of succinic dehydrogenase enzyme.Result: Histomorphologically the proventriculus of Guinea fowl was observed as the typical tubular component with four tunics from inside to outside as tunica mucosa, tunica sub mucosa, tunica muscularis and tunica serosa. The submucosal layer comprised with proventricular submucosal gland (PVSMG) which was encapsulated by elastic fibers. Tunica muscularis was inner longitudinal and outer circular layer, while the tunica serosa was observed with surrounding adipose tissue as the connective tissue constituent to endow the access of nutritional supply in the form of blood vessels. The luminal surface of proventricular submucosal glands has shown the significant activity of glycogen while intercalated, intralobular and interlobular ducts have exhibited the weak activity towards the same. The glandular cell rod of PVSMG, serosal layer and adjoining connective tissue with blood vessels has exhibited very weak activity of alkaline phosphatase. Mucosal folds and lumen of PVSMG has shown the weak activity of acidic phosphatase but the serosal limiting membrane has shown very weak activity. The succinic dehydrogenase activity was seen in the connective tissue septa of submucosal glandular cellular rods and the intense activity was observed at tunica muscularis.

Glandular structures in the major interlobular and extrapancreatic ducts in the guinea pig.

The morphology of the pancreatic duct system did not receive much attention as compared to the microanatomy of the exocrine and endocrine pancreas. The histological peculiarities of the excretory duct system are of major importance especially in laboratory animals like guinea pigs. The paper describes the histological peculiarities of the major interlobular and extrapancreatic ducts in guinea pigs. The pancreatic tissue samples were collected from five guinea pigs. For histological investigation, several pancreatic fragments underwent fixation in 10% buffered formalin and were later processed by the standard paraffin technique. Subsequentially, tissue sections were stained by Goldner's trichrome staining. The mucous substances were assessed by Alcian blue and Periodic acid-Schiff staining methods. The interlobular and main pancreatic ducts in the guinea pig present a simple columnar epithelium surrounded by a thick layer of dense connective tissue. The aforementioned epithelium of the main pancreatic ducts includes principal cells, goblet cells and basal cells. Additionally, the ductal epithelium presents occasional unicellular multiloculated intraepithelial mucous glands and prominent extraepithelial glands. The latter adopts a simple or compound tubular feature. The mucus elaborated by the three glandular types is mostly neutral in goblet cells, predominantly acidic in extraepithelial ductal glands, and a similar amount of acidic and neutral mucin in intraepithelial glands. In conclusion, the epithelium-associated mucous glands in the interlobular and main pancreatic ducts in the guinea pig are restricted not only to goblet cells. A substantial mucous discharge probably with a protecting role against irritative pancreatic juice derives from the main ductal intraepithelial and extraepithelial glands.

S2498 Vismodegib, a Hedgehog Pathway Inhibitor, Causing Severe Liver Injury

INTRODUCTION: Vismodegib, a hedgehog pathway inhibitor used to treat locally advanced and metastatic basal cell carcinoma, can lead to severe hepatotoxicity. Patients who develop nausea, loss of appetite, and dysgeusia should have liver enzymes evaluated. Early detection of liver insult could lead to early discontinuation of the drug to prevent worsening liver injury, further workup and unnecessary hospitalization. CASE DESCRIPTION/METHODS: A 53 year old female with invasive basal cell carcinoma on vismodegib, presented with loss of appetite, RUQ abdominal pain and jaundice. Labs revealed a total bilirubin of 7.4 mg/dL, alkaline phosphatase 545 IU/L, AST 163 IU/L, and ALT 471 IU/L. Viral hepatitis and autoimmune panel was unremarkable. MRCP and an endoscopic ultrasound did not show any biliary obstruction. However, the biliary ducts appeared unusually small. Her bilirubin continued to increase, and the idea of vismodegib causing cholestatic liver injury and vanishing bile duct syndrome was entertained. However, ERCP revealed a normal cholangiogram. Liver biopsy was pursued and showed marked zone 3 canalicula cholestasis and marked duct injury in portal tracts suggesting vismodegib causing cholestatic liver injury. DISCUSSION: There have been a few cases now reporting vismodegib-induced liver injury. Luckily our patient slowly improved with drug withdrawal. However, there has been life-threatening hepatotoxicity and even death, especially in patients taking drugs with potential hepatotoxic effects. Liver enzymes can mimic the pattern of acute viral or autoimmune hepatitis or ischemic liver injury. Our initial suspicion given our patient's MRCP and EUS findings, with bile ducts appearing abnormally small, was drug-induced vanishing bile duct syndrome. Vanishing bile duct syndrome in adults is typically caused by autoimmune diseases, neoplasms such as Hodgkin’s lymphoma, infections such as CMV and drugs such as allopurinol. The diagnosis is made through liver biopsy containing at least 10 portal tracts, showing loss of interlobular bile ducts in > 50% of the portal tracts. Clinically, patients will have fatigue, weight loss, loss of appetite, and abdominal pain as a result of intrahepatic cholestasis. Treatment includes discontinuation of offending drug but others have trialed ursodiol. Our patient’s liver biopsy did not suggest this rare syndrome but we suspect that if she had continued vismodegib, her outcome could have been worse and her liver biopsy could have progressed to vanishing bile duct syndrome.Figure 1.: Magnetic resonance cholangiopancreatography did not show any evidence of obstruction. Biliary ducts appeared small.Figure 2.: Endoscopic retrograde cholangiopancreatography was unremarkable, without evidence of obstruction.

S2617 Autoimmune Hepatitis vs Primary Biliary Cholangitis: A Case of Overlap Syndrome

INTRODUCTION: Immune-mediated liver diseases including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are rare. Overlap between these entities comprises an even smaller group with AIH-PBC being the most common. We present the case of a woman complaining of pruritus and elevated liver enzymes leading to diagnosis of AIH-PBC overlap syndrome. CASE DESCRIPTION/METHODS: A 43 year woman with history of hyperlipidemia presented with diffuse pruritus and bruising for 2 weeks. On presentation, the patient was hemodynamically stable. Her physical exam showed mild abdominal tenderness and excoriations on her extremities. Laboratory analysis demonstrated an elevated Alkaline phosphatase 1334, AST 243 and ALT 310. Total bilirubin was mildly elevated at 1.4, direct bilirubin 0.6 and GGT 1145. Hepatitis panel was non reactive. ANA screen was positive with titer 1:1280 in a dense fine speckled pattern. Anti-mitochondrial and anti-smooth muscle antibodies were negative. A liver biopsy denoted absence of interlobular bile ducts, portal lymphoplasmacytic infiltrates with interface hepatitis, mild portal fibrosis with no bridging fibrosis or cirrhosis and collections of histiocytes appearing as poorly formed granulomas. Upper endoscopy was unremarkable. Based on these findings, the diagnosis of AIH-PBC overlap was made. She was referred to transplant hepatology and was treated with ursodeoxycholic acid (UDCA), corticosteroids and mycophenylate mofetil. Subsequent testing showed significant improvement in liver function tests with normalization of bilirubin levels. DISCUSSION: AIH-PBC is the most common type of overlap syndrome found in approximately 8–10% in patients. Overlapping features include symptoms, clinical findings, biochemical tests, a variety of immunological findings and histology. These criteria were supported in our patient with findings of portal lymphoplasmacytic infiltrates with interface hepatitis, absence of interlobular bile ducts and collections of histiocytes appearing as granulomas on liver biopsy. More specifically our patient fell into the sub-entity, often named autoimmune cholangitis or AMA negative PBC which typically presents with elevated antinuclear antibodies with or without smooth muscle antibodies. Since most patients of AIH-PBC overlap syndrome required additional treatment with an immunosuppressive regimen in addition to UDCA, the distinction of this overlap condition should neither be delayed nor missed.Figure 1.: Lymphoplasmacytic infiltrates.

Distinct EpCAM-Positive Stem Cell Niches Are Engaged in Chronic and Neoplastic Liver Diseases.

In normal human livers, EpCAMpos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAMpos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAMpos progenitor cells within bile ductules are engaged in driving regenerative processes in chronic diseases affecting hepatocytes or interlobular bile ducts. The EpCAMpos population within peribiliary glands is activated when regenerative needs are finalized to repair large intra- or extra-hepatic bile ducts affected by chronic pathologies, including primary sclerosing cholangitis and ischemia-induced cholangiopathies after orthotopic liver transplantation. Finally, the presence of distinct EpCAMpos cell populations may explain the histological and molecular heterogeneity characterizing cholangiocarcinoma, based on the concept of multiple candidate cells of origin. This review aimed to describe the precise anatomical distribution of EpCAMpos populations within the liver and the biliary tree and to discuss their contribution in the pathophysiology of human liver diseases, as well as their potential role in regenerative medicine of the liver.

Antidiabetic property of Chrysophyllum albidumextract in Streptozotozin- induced diabetic rats

This study is aimed at evaluating the anti-diabetes property of Chrysophyllum albidum on Streptozotozininduced Diabetic mellitus in rats. Diabetic mellitus induced intraperitoneally with streptozotocin (STZ) using standard dose of 40 mg/kg after fasted for 12 hours as protocol implies. Blood glucose levels were determined using Accu-check glucometer before and during treatment of 10 and 30 mg/kg C. albidum when compared with Metformin and diabetic control groups. Animals whose blood glucose level was above 200 mg/dL were considered diabetic. After 28 days of treatment, blood and tissue samples were isolated for fasting blood sugar, haematological, bioassay and histopathological study using standard procedures. Result revealed a significant decrease (p<0.05) in the treated groups specifically at 30 mg/kg body C. albidum ethanol extract when compared with metformin and diabetic control group from weeks 0 to 5. The haematological result showed slight significant difference (p>0.05) now some parameters across treated groups excluding 10 mg/kg of C. albidum of MCH that showed a significant difference when compared with metformin and control group. Result showed a significant increase in the level of CAT, SOD, MDA and GST across the treated groups (10 and 30 mg/kg C. albidum) ethanol extract when compared with standard (10 mg/kg metformin) and diabetic control. The histopathological alteration observed in this study include; severe interlobular oedema and fatty droplets in the interlobular ducts and connective tissues. These alterations were prominent in the diabetic control group while 30 mg/kg of C. albidum showed prominent reduction in damage done by an anti-diabetonic agent (streptozotocin). This study showed that C. albidum is effective in the management of diabetes, which concord with its ethnomedicinal reports.

Features of the structural organization of the interlobular bile ducts under conditions of prolonged exposure to opioids in the experiment

The article contains new information on the current problem of the influence of endo- and exopathogenic factors on the structure of the digestive system. The purpose of the study was to establish the structural features of the interlobular bile ducts under the conditions of six weeks of exposure to nalbuphine in the experiment. The study was based on 30 white laboratory rats of male reproductive age. Histological sections of the liver were stained with hematoxylin and eosin according to conventional methods. The «Aver Media» computer system was used to photograph the micropreparations. The computer program ImageJ was used to measure the diameter of the lumen and the wall thickness of the interlobular bile duct. «Excel» and «Statistica» 6.0 software were used for statistical processing of the obtained digital data. The results of the study show that against the background of nalbuphine administration for six weeks there are morphological changes in the interlobular bile ducts of experimental animals, manifested by destructuring of the interlobular bile ducts, loss of their proper shape, expansion and unevenness of their lumens, deformation and thickening of the interstitial walls in 2-3 times, disorganization of cholangiocytes, thinning of the cell layer due to detachment of cholangiocytes, polymorphism of their nuclei, stratification, fragmentation of the lamina propria of the interlobular bile ducts, periductal edema, dilatation of interlobular portal tracts, "varicose" veins of the interlobular portal tracts, pronounced smooth muscle hyperplasia of the interlobular arteries, the presence of perivascular lymphocytic infiltrates. The data of the study can be used in practical medicine in the diagnosis and treatment of pathology of the bile ducts due to long-term use of opioids.

2062-P: Pancreatic Inflammation Implicates Increased Cellular Plasticity in the Pancreatic Duct Glands in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by endocrine/exocrine pancreas inflammation, fibrosis and, ultimately, decreased organ mass. Accumulating evidence suggests that this chronic inflammation may play a pivotal role in the initiation and progression of endogenous pancreatic cell plasticity. Pancreatic duct glands (PDGs), a potential stem/progenitor cell niche, represent a distinct anatomical compartment of the pancreas, forming blind-ending outpouchings from the main pancreatic duct and its branches. PDGs become activated in response to inflammation in T1D, evidenced by a high frequency of epithelial cell replication and an increase in progenitor-like cells. We addressed the hypothesis that in T1D, perturbation of hormone and non-hormone expressing cells in the interlobular ducts (ILD) and PDGs is a consequence of inflammation. Pancreatic sections from 21 T1D (disease duration 3 - 84 y) and 22 age-matched nondiabetic (ND) donors were evaluated for replication and expression of known pancreatic endocrine hormones in ducts and PDGs. We confirmed increased duct and PDG replication in T1D (T1D vs. ND— ILD: 2.8 ± 0.9 vs. 0.7 ± 0.1%, p<0.05; PDG: 3.4 ± 1.0 vs. 1.1 ± 0.4%, p<0.05) and reduced frequency of insulin expressing cells (T1D vs. ND— ILD: 0.0 ± 0.0 vs. 0.4 ± 0.1%, p<0.001; PDGs: 0.01 ± 0.01 vs. 0.8 ± 0.3%, p<0.05). The frequency of PDG cell replication was highest in T1D donors with acute pancreatitis. No differences were found in the frequency of other endocrine cell types regardless of the presence of pancreatic inflammation. These data suggest that increased pancreatic ductal cell replication in the PDG compartment of subjects with T1D is associated with sustained autoimmunity-related inflammation. Efforts are underway to determine specificity of pancreatic ductal cell changes to islet or acinar inflammation and the identity of replicating ILD and PDG cells, to better understand the mechanisms underlying pancreatic ductal cell plasticity. Disclosure S.S. Kulkarni: None. A.E. Butler: None. M.A. Atkinson: None.

Metabolism and disposition of oseltamivir (OS) in rats, determined by immunohistochemistry with monospecific antibody for OS or its active metabolite oseltamivir carboxylate (OC): A possibility of transporters dividing the drugs' excretion into the bile and kidney.

Among any drugs, no comparative pharmacological study on how prodrug and its active metabolite behave in animal bodies is available. Immunohistochemistry (IHCs) using newly prepared two monoclonal antibodies, AOS‐96 and AOC‐160, monospecific for oseltamivir (OS) and its metabolite oseltamivir carboxylate (OC) were developed, simultaneously detecting the uptake or excretion of OS and OC in the intestine, liver, and kidney of rats to which OS was orally administered. In the intestine, IHC for OS revealed OS highly distributed to the absorptive epithelia with heavily stained cytoplasmic small granules (CSGs). IHC for OC showed that OC also distributed highly in the epithelia, but without CSGs, suggesting that OS was partly converted to OC in the cells. In the liver, OS distributed in the hepatocytes and on their bile capillaries, as well as on the lumina from the bile capillaries to the interlobular bile ducts. OC distributed in the whole cell of the hepatocytes, but without CSGs nor on any lumina through the interlobular bile ducts. In the kidney, a few levels of OS distributed in the cytoplasm of almost all the renal tubule cells, but they contained numerous CSGs. In contrast, OC distributed highly in the proximal tubules, but very slightly in the lower renal tubules of the nephrons. Thus, it was concluded that the two drugs behave in completely different ways in rat bodies. This paper also discusses a possibility of the correlation of OS or OC levels in tissue cells with their known transporters.

Identification of Telocytes in the Pancreas of Turtles-A role in Cellular Communication.

The existence of telocytes (TCs) has not yet been established in the pancreases of aquatic reptiles. Here, we report TCs in the exocrine pancreas of Pelodiscus sinensis using transmission electron microscope (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) techniques. TCs surrounded the acini and ducts of the connective tissue of the exocrine pancreas and between lobules and gland cells. The cells were located preferably close to the blood vessels, interlobular ducts, and nerve fibers. Ultrastructurally, TCs exhibited small and large bodies with thick and thin portions, podoms, and podomers, and prolongations that form dichotomous branching with hetero-cellular and homo-cellular junctions. The podom (thick) portions showed caveolae, mitochondria, rough endoplasmic reticulum, and vesicles. The nucleus carries heterochromatin and is irregular in shape. The shape of TCs depends on the number of telopodes (Tps) bearing long, short, spindle, triangular, and “beads on a string” shapes with twisted, tortuous prolongations and ramifications. Shed extracellular vesicles and exosomes were found frequently released from projections and Tps within connective tissue in the vicinity of the acini and collagen fibers. IHC and IF results showed CD34+, α-SMA+, and vimentin+, long and triangle-shaped TCs, consistent with the TEM findings. The presence of shaded vesicles from TCs might implicate their possible role in immune surveillance, tissue regeneration as well as regulatory functions in the reptilian pancreas.

Canal of Hering loss is an initiating step for primary biliary cholangitis (PBC): A hypothesis

The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC. As a potential target of inflammatory or toxic injury, CoH loss may initiate rather than follow the cascade of events leading to duct injury and loss and their sequelae. Toxins may be exogenous in origin, such as environmental toxins or drug exposures, or endogenous, resulting from genetic or epigenetic alterations in canalicular bile transporters upstream from the CoH. In turn, this hypothesis suggests that loss of CoH would lead to altered bile flow and composition injurious to downstream bile ducts, because bile composition has not been modulated by normal CoH physiologic functions or because, in the absence of CoH, canalicular fluid flow into the biliary tree is disrupted interfering with soluble trophic factors important for bile duct integrity. Regardless of the pathogenic mechanism causing CoH loss, only following such loss would the characteristic diagnostic findings of PBC become evident: damage to downstream interlobular and sub-lobular bile ducts. To the extent that the causal mechanisms for CoH loss can be identified, clinical identification (as through early identification of CoH loss) and intervention (depending on the inciting cause) may offer promise for treatment of this enigmatic disease.

Inherited Cholestatic Diseases in the Era of Personalized Medicine.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-mack a video presentation of this article.

Etiologies of neonatal cholestasis at a tertiary hospital in Bangladesh

Background Neonatal cholestasis is an important etiology of chronic liver disease in young children. It has a varied etiology. There is considerable delay in presentation and diagnosis of neonatal cholestasis in Bangladesh. Lack of awareness and knowledge among the pediatricians regarding etiological diagnosis and outcome of neonatal cholestasis is the reasons for poor outcome in major portion of cases in Bangladesh.
 Objective To evaluate the etiological spectrum of neonatal cholestasis.
 Methods This retrospective study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. We reviewed medical records of children who were diagnosed with neonatal cholestasis. Complete diagnostic profiles of every cases with age of presentation, male-female ratio and final diagnosis were analyzed.
 Results A total of 114 children with neonatal cholestasis were evaluated. Subjects’ male-female ratio was 1.92: 1.0, and mean age at hospitalization was 92.7 (SD 39.5) days. Biliary atresia was the most common etiology (47.4%), followed by idiopathic neonatal hepatitis/INH (21.9%). Other identified etiologies were, toxoplasmosis, others (syphilis, varicella-zoster, parvovirus b19), rubella, cytomegalovirus (CMV), and herpes/TORCH infection (8.61%), progressive familial intrahepatic cholestasis/PFIC (4.4%), galactosemia (4.4%), choledochal cyst (3.5%), sepsis (1.8%), urinary tract infection/UTI (1.8%), hypothyroidism (1.8%), lipid storage disease/Niemann-Pick disease (0.9%), non-syndromic paucity of interlobular bile ducts (2.67%), and Caroli’s disease (0.9%).
 Conclusion In Bangladesh, neonatal cholestasis cases are most often due to obstructive causes, particularly biliary atresia. Idiopathic (INH), infectious (primarily TORCH), metabolic, and endocrine causes followed in terms of frequency.

Etiologies of neonatal cholestasis at a tertiary hospital in Bangladesh

Background Neonatal cholestasis is an important etiology of chronic liver disease in young children. It has a varied etiology. There is considerable delay in presentation and diagnosis of neonatal cholestasis in Bangladesh. Lack of awareness and knowledge among the pediatricians regarding etiological diagnosis and outcome of neonatal cholestasis is the reasons for poor outcome in major portion of cases in Bangladesh.
 Objective To evaluate the etiological spectrum of neonatal cholestasis.
 Methods This retrospective study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. We reviewed medical records of children who were diagnosed with neonatal cholestasis. Complete diagnostic profiles of every cases with age of presentation, male-female ratio and final diagnosis were analyzed.
 Results A total of 114 children with neonatal cholestasis were evaluated. Subjects’ male-female ratio was 1.92: 1.0, and mean age at hospitalization was 92.7 (SD 39.5) days. Biliary atresia was the most common etiology (47.4%), followed by idiopathic neonatal hepatitis/INH (21.9%). Other identified etiologies were, toxoplasmosis, others (syphilis, varicella-zoster, parvovirus b19), rubella, cytomegalovirus (CMV), and herpes/TORCH infection (8.61%), progressive familial intrahepatic cholestasis/PFIC (4.4%), galactosemia (4.4%), choledochal cyst (3.5%), sepsis (1.8%), urinary tract infection/UTI (1.8%), hypothyroidism (1.8%), lipid storage disease/Niemann-Pick disease (0.9%), non-syndromic paucity of interlobular bile ducts (2.67%), and Caroli’s disease (0.9%).
 Conclusion In Bangladesh, neonatal cholestasis cases are most often due to obstructive causes, particularly biliary atresia. Idiopathic (INH), infectious (primarily TORCH), metabolic, and endocrine causes followed in terms of frequency.