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  1. Article ; Online: Practice Patterns Affecting Delays in Care of Testicular Torsion.

    Zhao, Kelley / Lu, Jennifer Y / Shkolnik, Brian / Davis, Rachel Bennett

    Urology

    2023  Volume 184, Page(s) 83–86

    Abstract: Objectives: To compare impact of day or on-call team, pediatric or adult attending, and patient age on testicular torsion management and outcomes.: Methods: A retrospective study of patients with testicular torsion between 2012 and 2022 at a single ... ...

    Abstract Objectives: To compare impact of day or on-call team, pediatric or adult attending, and patient age on testicular torsion management and outcomes.
    Methods: A retrospective study of patients with testicular torsion between 2012 and 2022 at a single institution was conducted. Variables impacting management time were assessed using univariate analyses.
    Results: One hundred and thirty-four patients were included: 49 underwent orchiectomies and 84 underwent orchiopexies. There was no significant difference between efficiency of on-call vs day team regarding time to ultrasound or time to operating room (OR). There were no significant differences between pediatric vs adult attending surgeons for time to surgery, intraoperative length of surgery, or testicular salvage rates. However, when patients were stratified by age greater or younger than 18years, older patients had significantly longer symptom duration (91.9 vs 20.0 minutes, P = .005), time to receive an ultrasound from emergency room registration (152 vs 87 minutes, P < .001), time to OR from emergency room registration (268 vs 185 minutes, P < .001), and time to OR from ultrasound read (187 vs 123 minutes, P = .03). Older patients also had lower rates of testicular salvage approaching significance (orchiectomy rate 48.8% vs 31.5%, P = .057).
    Conclusion: While no significant delays in testicular torsion management were detected between management by on-call vs day team nor pediatric vs adult attending, increased age of patient was associated with delays in definitive surgical management. Greater index of suspicion for testicular torsion diagnosis in adult patients may improve the rate of testicular salvage.
    MeSH term(s) Adult ; Male ; Humans ; Child ; Adolescent ; Spermatic Cord Torsion/diagnosis ; Spermatic Cord Torsion/surgery ; Retrospective Studies ; Orchiectomy ; Emergency Service, Hospital ; Health Facilities
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 192062-5
    ISSN 1527-9995 ; 0090-4295
    ISSN (online) 1527-9995
    ISSN 0090-4295
    DOI 10.1016/j.urology.2023.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Is the "Pandemic Diet" Nonlithogenic?

    Shkolnik, Brian / Zhao, Kelley / Lu, Jennifer Y / Kothari, Pankti / Herfel, Scott / Schulsinger, Hailey / Schulsinger, David

    Journal of endourology

    2024  

    Abstract: Introduction and Objective: ...

    Abstract Introduction and Objective:
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 356931-7
    ISSN 1557-900X ; 0892-7790
    ISSN (online) 1557-900X
    ISSN 0892-7790
    DOI 10.1089/end.2023.0535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 20-HETE Activates the Transcription of Angiotensin-Converting Enzyme via Nuclear Factor-κB Translocation and Promoter Binding.

    Garcia, Victor / Shkolnik, Brian / Milhau, Laura / Falck, John R / Schwartzman, Michal Laniado

    The Journal of pharmacology and experimental therapeutics

    2016  Volume 356, Issue 3, Page(s) 525–533

    Abstract: Increased vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 arachidonic acid metabolite, promotes vascular dysfunction, injury, and hypertension that is dependent, in part, on the renin angiotensin system (RAS). We have shown that, in ...

    Abstract Increased vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 arachidonic acid metabolite, promotes vascular dysfunction, injury, and hypertension that is dependent, in part, on the renin angiotensin system (RAS). We have shown that, in human microvascular endothelial cells, 20-HETE increases angiotensin-converting enzyme (ACE) mRNA, protein, and ACE activity via an epidermal growth factor receptor (EGFR)/tyrosine kinase/mitogen-activated protein kinase (MAPK)/inhibitor of κB kinase (IKK)β-mediated signaling pathway. In this work, we show that, similar to epidermal growth factor (EGF), 20-HETE (10 nM) activates EGFR by stimulating tyrosine phosphorylation; however, unlike 20-HETE, EGF does not induce ACE expression, and pretreatment with a neutralizing antibody against EGF does not prevent the 20-HETE-mediated ACE induction. Inhibition of nuclear factor κB (NF-κB) activation prevented the 4.58-fold (±0.78; P < 0.05) 20-HETE-mediated induction of ACE. The 20-HETE increased NF-κB-binding activity in nuclear extracts and the activity of both the somatic and germinal ACE promoters by 4.37-fold (±0.18; P < 0.05) and 2.53-fold (± 0.24; P < 0.05), respectively. The 20-HETE-stimulated ACE promoter activity was abrogated by the 20-HETE antagonist 20-hydroxy-6,15-eicosadienoic acid and by inhibitors of EGFR, MAPK, IKKβ, and NF-κB activation. Sequence analysis demonstrated the presence of two and one putative NF-κB binding sites on the human somatic and germinal ACE promoters, respectively. Chromatin immunoprecipitation assay indicated that 20-HETE stimulates the translocation and subsequent binding of NF-κB to each of the putative binding sites (S1, 3.43 ± 0.3-fold enrichment versus vehicle; S2, 3.72 ± 0.68-fold enrichment versus vehicle; S3, 3.20 ± 0.18-fold enrichment versus vehicle; P < 0.05). This is the first study to identify NF-κB as a transcriptional factor for ACE and to implicate a distinct EGFR/MAPK/IKK/NF-κB signaling cascade underlying 20-HETE-mediated transcriptional activation of ACE mRNA and stimulation of ACE activity.
    MeSH term(s) Cells, Cultured ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Humans ; Hydroxyeicosatetraenoic Acids/pharmacology ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Promoter Regions, Genetic/drug effects ; Promoter Regions, Genetic/physiology ; Protein Binding/physiology ; Transcription, Genetic/drug effects ; Transcription, Genetic/physiology
    Chemical Substances Hydroxyeicosatetraenoic Acids ; NF-kappa B ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2016-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3106-9
    ISSN 1521-0103 ; 0022-3565
    ISSN (online) 1521-0103
    ISSN 0022-3565
    DOI 10.1124/jpet.115.229377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (G

    Garcia, Victor / Gilani, Ankit / Shkolnik, Brian / Pandey, Varunkumar / Zhang, Frank Fan / Dakarapu, Rambabu / Gandham, Shyam K / Reddy, N Rami / Graves, Joan P / Gruzdev, Artiom / Zeldin, Darryl C / Capdevila, Jorge H / Falck, John R / Schwartzman, Michal Laniado

    Circulation research

    2017  Volume 120, Issue 11, Page(s) 1776–1788

    Abstract: Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as ... ...

    Abstract Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases.
    Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists. The present study was undertaken to identify a receptor to which 20-HETE binds and through which it activates a signaling cascade that culminates in many of the functional outcomes attributed to 20-HETE in vitro and in vivo.
    Methods and results: Using crosslinking analogs, click chemistry, binding assays, and functional assays, we identified G-protein receptor 75 (GPR75), currently an orphan G-protein-coupled receptor (GPCR), as a specific target of 20-HETE. In cultured human endothelial cells, 20-HETE binding to GPR75 stimulated Gα
    Conclusions: This is the first report to identify a GPCR target for an eicosanoid of this class. The discovery of 20-HETE-GPR75 pairing presented here provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases.
    MeSH term(s) Animals ; Cells, Cultured ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiology ; Humans ; Hydroxyeicosatetraenoic Acids/metabolism ; Hydroxyeicosatetraenoic Acids/pharmacology ; Hydroxyeicosatetraenoic Acids/toxicity ; Hypertension/chemically induced ; Hypertension/metabolism ; Male ; Mice ; Mice, Transgenic ; Protein Binding/physiology ; Rats ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Vascular Remodeling/drug effects ; Vascular Remodeling/physiology
    Chemical Substances GPR75 protein, human ; Hydroxyeicosatetraenoic Acids ; Receptors, G-Protein-Coupled ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3)
    Language English
    Publishing date 2017-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.116.310525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Angiotensin II receptor blockade or deletion of vascular endothelial ACE does not prevent vascular dysfunction and remodeling in 20-HETE-dependent hypertension.

    Garcia, Victor / Joseph, Gregory / Shkolnik, Brian / Ding, Yan / Zhang, Frank Fan / Gotlinger, Katherine / Falck, John R / Dakarapu, Rambabu / Capdevila, Jorge H / Bernstein, Kenneth E / Schwartzman, Michal Laniado

    American journal of physiology. Regulatory, integrative and comparative physiology

    2015  Volume 309, Issue 1, Page(s) R71–8

    Abstract: Increased vascular 20-HETE is associated with hypertension and activation of the renin-angiotensin system (RAS) through induction of vascular angiotensin-converting enzyme (ACE) expression. Cyp4a12tg mice, whose Cyp4a12-20-HETE synthase expression is ... ...

    Abstract Increased vascular 20-HETE is associated with hypertension and activation of the renin-angiotensin system (RAS) through induction of vascular angiotensin-converting enzyme (ACE) expression. Cyp4a12tg mice, whose Cyp4a12-20-HETE synthase expression is under the control of a tetracycline (doxycycline, DOX) promoter, were used to assess the contribution of ACE/RAS to microvascular remodeling in 20-HETE-dependent hypertension. Treatment of Cyp4a12tg mice with DOX increased systolic blood pressure (SBP; 136 ± 2 vs. 102 ± 1 mmHg; P < 0.05), and this increase was prevented by administration of 20-HEDGE, lisinopril, or losartan. DOX-induced hypertension was associated with microvascular dysfunction and remodeling of preglomerular microvessels, which was prevented by 20-HEDGE, a 20-HETE antagonist, yet only lessened, but not prevented, by lisinopril or losartan. In ACE 3/3 mice, which lack vascular endothelial ACE, administration of 5α-dihydrotestosterone (DHT), a known inducer of 20-HETE production, increased SBP; however, the increase was about 50% of that in wild-type (WT) mice (151 ± 1 vs. 126 ± 1 mmHg). Losartan and 20-HEDGE prevented the DHT-induced increase in SBP in WT and ACE 3/3 mice. DHT treatment increased 20-HETE production and microvascular remodeling in WT and ACE 3/3 mice; however, remodeling was attenuated in the ACE 3/3 mice as opposed to WT mice (15.83 ± 1.11 vs. 22.17 ± 0.92 μm; P < 0.05). 20-HEDGE prevented microvascular remodeling in WT and ACE 3/3 mice, while losartan had no effect on microvascular remodeling in ACE 3/3. Taken together, these results suggest that RAS contributes to 20-HETE-mediated microvascular remodeling in hypertension and that 20-HETE-driven microvascular remodeling independent of blood pressure elevation does not fully rely on ACE activity in the vascular endothelium.
    MeSH term(s) Angiotensin II/metabolism ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Antihypertensive Agents/pharmacology ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Dihydrotestosterone ; Disease Models, Animal ; Endothelial Cells/drug effects ; Endothelial Cells/enzymology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/enzymology ; Endothelium, Vascular/physiopathology ; Female ; Hydroxyeicosatetraenoic Acids/metabolism ; Hypertension/chemically induced ; Hypertension/drug therapy ; Hypertension/enzymology ; Hypertension/genetics ; Hypertension/physiopathology ; Male ; Mice, Transgenic ; Microvessels/drug effects ; Microvessels/enzymology ; Microvessels/physiopathology ; Peptidyl-Dipeptidase A/deficiency ; Peptidyl-Dipeptidase A/genetics ; Renin-Angiotensin System/drug effects ; Time Factors ; Vascular Remodeling/drug effects
    Chemical Substances Angiotensin II Type 1 Receptor Blockers ; Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Hydroxyeicosatetraenoic Acids ; Dihydrotestosterone (08J2K08A3Y) ; Angiotensin II (11128-99-7) ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2015-04-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603839-6
    ISSN 1522-1490 ; 0363-6119
    ISSN (online) 1522-1490
    ISSN 0363-6119
    DOI 10.1152/ajpregu.00039.2015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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