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  1. Article ; Online: Alkaline phosphatase: Need for an earlier time-table.

    Javitt, Norman B

    Liver international : official journal of the International Association for the Study of the Liver

    2023  Volume 43, Issue 9, Page(s) 2046

    MeSH term(s) Humans ; Alkaline Phosphatase ; Liver
    Chemical Substances Alkaline Phosphatase (EC 3.1.3.1)
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2102783-3
    ISSN 1478-3231 ; 1478-3223
    ISSN (online) 1478-3231
    ISSN 1478-3223
    DOI 10.1111/liv.15675
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  2. Article ; Online: Hepatic Bile Formation: Developing a New Paradigm.

    Javitt, Norman B

    Pharmacological reviews

    2023  Volume 75, Issue 5, Page(s) 1036–1042

    Abstract: In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium ... ...

    Abstract In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium taurocholate, and the hormone secretin to stimulate bile flow led to conflicting data and a moratorium on attempts to further develop the initial proposal. However, current data amplify the initial proposal and indicate both paracellular and transcellular water flow into hepatic ductules and the canalicular conduit in response to an osmotic gradient. Also, the need to further modify the initial proposal became apparent with the recognition that bile acid aggregates (micelles), which form in the canalicular conduit, generate lecithin-cholesterol vesicles that contain water unrelated to an osmotic gradient. As part of this development is the recent introduction of the fluorescent localization after photobleaching technique for direct determination of hepatic duct flow and clarification of the role of biomarkers such as mannitol and polyethylene glycol 900. With the new paradigm, these biomarkers may prove useful for quantifying paracellular and transcellular water flow, respectively. SIGNIFICANCE STATEMENT: It is essential to identify and characterize all the sites for water flow during hepatic bile formation to obtain more precision in evaluating the causes and possible therapeutic approaches to cholestatic syndromes. Updating the Sperber proposal provides a new paradigm that addresses the advances in knowledge that have occurred.
    MeSH term(s) Humans ; Bile ; Liver ; Bile Acids and Salts ; Cholestasis ; Water
    Chemical Substances Bile Acids and Salts ; Water (059QF0KO0R)
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 209898-2
    ISSN 1521-0081 ; 0031-6997
    ISSN (online) 1521-0081
    ISSN 0031-6997
    DOI 10.1124/pharmrev.122.000799
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  3. Article ; Online: Letter to the editor: Hyperosmolarity during hepatic bile formation: Overlooked significance.

    Javitt, Norman B

    Hepatology (Baltimore, Md.)

    2022  Volume 76, Issue 3, Page(s) E57

    MeSH term(s) Bile ; Liver
    Language English
    Publishing date 2022-05-26
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.32482
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  4. Article ; Online: Obeticholic acid and hepatic bile acids: Excellent study faulty conclusion.

    Javitt, Norman B

    Journal of hepatology

    2021  Volume 74, Issue 5, Page(s) 1267

    Language English
    Publishing date 2021-01-26
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2021.01.031
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  5. Article ; Online: Letter to the Editor: Intravital Dynamic and Correlative Imaging Reveals Diffusion-Dominated Canalicular and Flow-Augmented Ductular Bile Flux.

    Javitt, Norman B

    Hepatology (Baltimore, Md.)

    2021  Volume 74, Issue 2, Page(s) 1131–1132

    MeSH term(s) Bile ; Bile Acids and Salts ; Bile Canaliculi
    Chemical Substances Bile Acids and Salts
    Language English
    Publishing date 2021-06-22
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.31746
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  6. Article ; Online: Letter to the Editor: Blocking Sodum-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice.

    Javitt, Norman B

    Hepatology (Baltimore, Md.)

    2020  Volume 72, Issue 5, Page(s) 1885

    MeSH term(s) Animals ; Cholesterol ; Mice ; Peptides ; Phospholipids ; Sodium ; Taurocholic Acid
    Chemical Substances Peptides ; Phospholipids ; Taurocholic Acid (5E090O0G3Z) ; Cholesterol (97C5T2UQ7J) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2020-10-19
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.31292
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  7. Article ; Online: Hepatic bile formation: bile acid transport and water flow into the canalicular conduit.

    Javitt, Norman B

    American journal of physiology. Gastrointestinal and liver physiology

    2020  Volume 319, Issue 5, Page(s) G609–G618

    Abstract: Advances in molecular biology identifying the many carrier-mediated organic anion transporters and advances in microscopy that have provided a more detailed anatomy of the canalicular conduit make updating the concept of osmotically determined ... ...

    Abstract Advances in molecular biology identifying the many carrier-mediated organic anion transporters and advances in microscopy that have provided a more detailed anatomy of the canalicular conduit make updating the concept of osmotically determined canalicular flow possible. For the most part water flow is not transmembrane but via specific pore proteins in both the hepatocyte and the tight junction. These pores independently regulate the rate at which water flows in response to an osmotic gradient and therefore are determinants of canalicular bile acid concentration. Review of the literature indicates that the initial effect on hepatic bile flow of cholestatic agents such as Thorazine and estradiol 17β-glucuronide are on water flow and not bile salt export pump-mediated bile acid transport and thus provides new approaches to the pathogenesis of drug-induced liver injury. Attaining a micellar concentration of bile acids in the canaliculus is essential to the formation of cholesterol-lecithin vesicles, which mostly occur in the periportal region of the canalicular conduit. The other regions, midcentral and pericentral, may transport lesser amounts of bile acid but augment water flow. Broadening the concept of how hepatic bile flow is initiated, provides new insights into the pathogenesis of canalicular cholestasis.
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily B, Member 11 ; Animals ; Bile/metabolism ; Bile Acids and Salts/metabolism ; Bile Canaliculi/metabolism ; Biological Transport ; Body Water/metabolism ; Humans ; Liver/metabolism
    Chemical Substances ATP Binding Cassette Transporter, Subfamily B, Member 11 ; Bile Acids and Salts
    Language English
    Publishing date 2020-09-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00078.2020
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  8. Article ; Online: Letter to the Editor: On the mechanisms of biliary flux.

    Javitt, Norman B / Boyer, James L

    Hepatology (Baltimore, Md.)

    2021  Volume 75, Issue 2, Page(s) 492–493

    MeSH term(s) Biliary Tract
    Language English
    Publishing date 2021-12-15
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.32167
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  9. Article ; Online: Fasting and postprandial serum bile acids after RYGB surgery.

    Javitt, Norman B

    Scandinavian journal of gastroenterology

    2018  Volume 53, Issue 10-11, Page(s) 1425–1426

    MeSH term(s) Bile Acids and Salts/blood ; Fasting/blood ; Gastric Bypass ; Humans ; Postprandial Period ; Weight Loss/physiology
    Chemical Substances Bile Acids and Salts
    Language English
    Publishing date 2018-10-08
    Publishing country England
    Document type Letter
    ZDB-ID 82042-8
    ISSN 1502-7708 ; 0036-5521
    ISSN (online) 1502-7708
    ISSN 0036-5521
    DOI 10.1080/00365521.2018.1518483
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  10. Article ; Online: Breast cancer and (25R)-26-hydroxycholesterol.

    Javitt, Norman B

    Steroids

    2015  Volume 104, Page(s) 61–64

    Abstract: 25R)-26-Hydroxycholesterol (27-hydroxycholesterol) has been found to accumulate in breast tissue and to stimulate tumor growth via the estrogen receptor. Although most tissues express CYP27A1, the highest levels are in macrophages and most attention had ...

    Abstract (25R)-26-Hydroxycholesterol (27-hydroxycholesterol) has been found to accumulate in breast tissue and to stimulate tumor growth via the estrogen receptor. Although most tissues express CYP27A1, the highest levels are in macrophages and most attention had been given to the production of 27-hydroxycholesterol in sub-endothelial macrophages as part of reverse cholesterol transport. In view of the newly identified biologic activity, it is important to consider the determinants of the levels of 27-hydroxycholesterol in macrophages that infiltrate breast tissue. Among these determinants are the oxysterol binding proteins expressed in macrophages, the level of expression of CYP7B1, the oxysterol 7 alpha hydroxylase that generates an inactive triol, and further oxidation of 27-hydroxycholestrol to the C27 acid by multifunctional CYP27A1. Transport of 27-hydroxycholesterol from macrophages to plasma is HDL-associated. In many tissues the ratio of 27-hydroxycholesterol to cholesterol (ng/μg) is higher than that in plasma. Tamoxifen, an effective estrogen receptor antagonist that prevents breast cancer, also has the biologic property of blocking several steps in the lanosterol to cholesterol metabolic pathway. In genetically disposed women, tamoxifen may increase the amount of 27-hydroxycholesterol in breast tissue.
    MeSH term(s) Animals ; Antineoplastic Agents, Hormonal/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Humans ; Hydroxycholesterols/analysis ; Hydroxycholesterols/antagonists & inhibitors ; Hydroxycholesterols/metabolism ; Macrophages/chemistry ; Macrophages/metabolism ; Receptors, Estrogen/antagonists & inhibitors ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology
    Chemical Substances Antineoplastic Agents, Hormonal ; Hydroxycholesterols ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45) ; 27-hydroxycholesterol (6T2NA6P5SQ)
    Language English
    Publishing date 2015-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2015.08.012
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