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  • 1
    Online Resource
    Online Resource
    S. Karger AG ; 2021
    In:  Medical Cannabis and Cannabinoids Vol. 4, No. 2 ( 2021-6-21), p. 97-106
    In: Medical Cannabis and Cannabinoids, S. Karger AG, Vol. 4, No. 2 ( 2021-6-21), p. 97-106
    Abstract: For centuries, cannabis and its components have been used to manage a wide variety of symptoms associated with many illnesses. Gastrointestinal (GI) diseases are no exception in this regard. Individuals suffering from inflammatory bowel disease (IBD) are among those who have sought out the ameliorating properties of this plant. As legal limitations of its use have eased, interest has grown from both patients and their providers regarding the potential of cannabis to be used in the clinical setting. Similarly, a growing number of animal and human studies have been undertaken to evaluate the impact of cannabis and cannabinoid signaling elements on the natural history of IBD and its associated complications. There is little clinical evidence supporting the ability of cannabis or related products to treat the GI inflammation underlying these disorders. However, 1 recurring theme from both animal and human studies is that these agents have a significant impact on several IBD-related symptoms, including abdominal pain. In this review, we discuss the role of cannabis and cannabinoid signaling in visceral pain perception, what is currently known regarding the efficacy of cannabis and its derivatives for managing pain, related symptoms and inflammation in IBD, and what work remains to effectively utilize cannabis and its derivatives in the clinical setting.
    Type of Medium: Online Resource
    ISSN: 2504-3889
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2908431-3
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 2017
    In:  American Journal of Physiology-Renal Physiology Vol. 313, No. 2 ( 2017-08-01), p. F522-F534
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 313, No. 2 ( 2017-08-01), p. F522-F534
    Abstract: Novel therapeutic interventions for preventing or attenuating kidney injury following ischemia-reperfusion injury (IRI) remain a focus of significant interest. Currently, there are no definitive therapeutic or preventive approaches available for ischemic acute kidney injury (AKI). Our objective is to determine 1) whether renal arginase activity or expression is increased in renal IRI, and 2) whether arginase plays a role in development of renal IRI. The impact of arginase activity and expression on renal damage was evaluated in male C57BL/6J (wild type) and arginase-2 (ARG2)-deficient ( Arg2 −/− ) mice subjected to bilateral renal ischemia for 28 min, followed by reperfusion for 24 h. ARG2 expression and arginase activity significantly increased following renal IRI, paralleling the increase in kidney injury. Pharmacological blockade or genetic deficiency of Arg2 conferred kidney protection in renal IRI. Arg2 −/− mice had significantly attenuated kidney injury and lower plasma creatinine and blood urea nitrogen levels after renal IRI. Blocking arginases using S-(2-boronoethyl)-l-cysteine (BEC) 18 h before ischemia mimicked arginase deficiency by reducing kidney injury, histopathological changes and kidney injury marker-1 expression, renal apoptosis, kidney inflammatory cell recruitment and inflammatory cytokines, and kidney oxidative stress; increasing kidney nitric oxide (NO) production and endothelial NO synthase (eNOS) phosphorylation, kidney peroxisome proliferator-activated receptor-γ coactivator-1α expression, and mitochondrial ATP; and preserving kidney mitochondrial ultrastructure compared with vehicle-treated IRI mice. Importantly, BEC-treated eNOS-knockout mice failed to reduce blood urea nitrogen and creatinine following renal IRI. These findings indicate that ARG2 plays a major role in renal IRI, via an eNOS-dependent mechanism, and that blocking ARG2 activity or expression could be a novel therapeutic approach for prevention of AKI.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2017
    detail.hit.zdb_id: 1477287-5
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 2010
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 298, No. 5 ( 2010-05), p. L678-L686
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 298, No. 5 ( 2010-05), p. L678-L686
    Abstract: Prolonged exposure to hyperoxia contributes to aberrant lung growth in premature infants. Of the deleterious effects induced by hyperoxia, alterations in protein synthesis are likely to be of great importance to the developing lung. Regulation of mRNA translation occurs predominantly at the level of initiation via control of mRNA/ribosome binding by proteins known as eukaryotic initiation factors (eIF). Although hyperoxia is known to suppress mRNA translation in adult lungs, little is known regarding the effects in newborns or the involved mechanism. This study was performed to determine the effect of exposure to 95% O 2 on pulmonary protein synthesis in 4-day-old Sprague-Dawley rat pups. We found that hyperoxia suppressed the incorporation of [ 3 H]phenylalanine into lung protein over time, resulting in a 23% reduction after 72 h compared with pups reared in room air. This effect was preceded by a shift in total lung RNA to lower order polysomes. Hyperoxia increased eIF4G-eIF4E binding, a surrogate maker of eIF4F complex assembly, and initially activated, then suppressed, the phosphorylation of ribosomal S6 kinase 1 and ribosomal S6 protein, downstream targets of mammalian target of rapamycin. Exposure to 95% O 2 enhanced the phosphorylation of the translational repressor eIF2α in whole lung extracts and the immunoreactivity of phosphorylated eIF2α in epithelial cells. Cell culture studies further demonstrated that hyperoxia increases eIF2α phosphorylation in lung epithelial cells, but not in lung fibroblasts. These findings illustrate that hyperoxia-induced suppression of mRNA translation in the newborn lung is accompanied by increased phosphorylation of eIF2α in the epithelium.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2012
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 302, No. 1 ( 2012-01-01), p. L27-L35
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 302, No. 1 ( 2012-01-01), p. L27-L35
    Abstract: Diverse environmental stresses stimulate eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, leading to a stress-resistant state characterized by global attenuation of protein synthesis and induction of cytoprotective genes. The signal transduction network culminating in these effects is referred to as the integrated stress response (ISR) or, when initiated by misfolded proteins within the endoplasmic reticulum (ER), the unfolded protein response (UPR). Given that we previously reported that exposure of 4-day-old Sprague-Dawley rats to 95% O 2 (Ox) diminishes global pulmonary protein synthesis and increases eIF2α phosphorylation, we conducted the current study to determine whether Ox activates the ISR or UPR. We found that Ox-induced alterations in ER morphology of alveolar type II cells and interstitial fibroblasts were not associated with activation of the UPR sensors PERK or activating transcription factor (ATF) 6 or with X-box binding protein-1 mRNA splicing in whole lung extracts. Exposure to Ox enhanced ATF4 immunoreactivity and nuclear protein content, followed by a 2- and 5-fold increase in ATF3 protein and mRNA expression, respectively. The accumulation of nuclear ATF4 protein coincided with induction of glutamate-cysteine ligase catalytic subunit, an ISR-responsive gene. Immunohistochemistry revealed that changes in ATF3/4 expression were prominent in the alveolus, whereas primary cell culture implicated epithelial and endothelial cells as targets. Finally, induction of ISR intermediates in the intact lung occurred in the absence of the phosphorylation of PKR, JNK, ERK1/2, and p38 MAPK. These findings demonstrate that Ox activates the ISR within the newborn lung and highlight regional and cell-specific alterations in the expression ISR transcription factors that regulate redox balance.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2012
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2014
    In:  Molecular and Cellular Biology Vol. 34, No. 9 ( 2014-05-01), p. 1659-1669
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 34, No. 9 ( 2014-05-01), p. 1659-1669
    Type of Medium: Online Resource
    ISSN: 1098-5549
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2014
    detail.hit.zdb_id: 1474919-1
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  • 6
    Online Resource
    Online Resource
    American Society for Pharmacology & Experimental Therapeutics (ASPET) ; 2021
    In:  Journal of Pharmacology and Experimental Therapeutics Vol. 376, No. 2 ( 2021-02), p. 204-212
    In: Journal of Pharmacology and Experimental Therapeutics, American Society for Pharmacology & Experimental Therapeutics (ASPET), Vol. 376, No. 2 ( 2021-02), p. 204-212
    Type of Medium: Online Resource
    ISSN: 0022-3565 , 1521-0103
    Language: English
    Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
    Publication Date: 2021
    detail.hit.zdb_id: 1475023-5
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2014
    In:  Inflammatory Bowel Diseases Vol. 20 ( 2014-12), p. S92-S93
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 20 ( 2014-12), p. S92-S93
    Type of Medium: Online Resource
    ISSN: 1078-0998
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Inflammatory Bowel Diseases Vol. 27, No. Supplement_1 ( 2021-01-21), p. S54-S55
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 27, No. Supplement_1 ( 2021-01-21), p. S54-S55
    Abstract: Polysubstance Use (PSU), the use of two or more substances of abuse, has been associated with increased risk for development of psychiatric conditions and early death compared to both monosubstance use or no substance use. The vast majority of clinical research on prescription or recreational drug consumption in patients with inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and ulcerative colitis (UC), has focused on use of individual substances. We evaluated the incidence and impact of PSU in IBD and assessed potential predisposing factors in this setting. Methods We performed a retrospective analysis using a consented IBD natural history registry from a single tertiary care referral center between 1/1/2015–8/31/2019. Demographics, endoscopic severity (using Mayo endoscopy sub-score for UC and Simple Endoscopic Score for CD), totals and sub-scores of surveys (Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, Hospital Anxiety and Depression Scale, Short IBD Questionnaire) assessing for symptoms (abdominal pain, fatigue, anxiety/depression, gas, diarrhea, rectal bleeding, and fecal urgency), substance use (tobacco, alcohol, marijuana, cocaine, methamphetamine, heroin, opiates, or benzodiazepine), and antidepressant or anxiolytic medication were abstracted. PSU was defined as concurrent use of two or more non-prescription drugs or substances, and healthcare resource utilization was defined as any IBD-related imaging, emergency room visit, hospitalization, or surgery over the prior 12 months. We computed descriptive statistics and performed contingency table analyses in order to identify associations between PSU and a variety of demographic and clinical characteristics. Multivariable logistic regression models were fit incorporating the clinical factors described above. Results 315 consecutively enrolled IBD patients (166f:149m; 214 CD and 101 UC) were included. Sixty-six patients (21.0%) were polysubstance users. Of these patients, 40.9% had moderate to severe disease activity, 47.0% had extra-intestinal manifestations (EIM), and 36.4% demonstrated an anxious or depressed state. EIM and antidepressant or anxiolytic use were positively associated with PSU on bivariate analysis (Table 1) and multivariable analysis (Table 2). Conclusions PSU is common in IBD, including both CD and UC. Interestingly, disease activity, IBD therapy type, and IBD-related symptoms were not associated with PSU. EIM and antidepressant or anxiolytic use were the only statistically significant predictors of PSU among patients with IBD in the multivariable logistic regression models. Our study represents the first evaluation of PSU within IBD and reinforces the importance of appropriate substance use screening among IBD patients, particularly among those with EIM and antidepressant or anxiolytic use.
    Type of Medium: Online Resource
    ISSN: 1078-0998 , 1536-4844
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 9
    In: Journal of Digestive Diseases, Wiley, Vol. 22, No. 12 ( 2021-12), p. 706-713
    Abstract: We aimed to evaluate the incidence, predisposing factors and impacts of polysubstance use (PSU) (ie, the concurrent use or abuse of two or more drugs or substances) in inflammatory bowel disease (IBD). Methods Data of patients enrolled between 1 January 2015 and 31 August 2019 from a single tertiary care referral center were retrospectively collected. Patients’ baseline and clinical characteristics and their antidepressant and/or anxiolytic medications were abstracted. Associations between PSU and patients’ characteristics were analyzed. Multivariate logistic regression models were fit, incorporating significant clinical factors. Results Altogether 315 patients with IBD (166 women, 149 men; 214 with Crohn's disease and 101 ulcerative colitis) were enrolled. Of them, 66 (21.0%) exhibited PSU (CD 21.5%, UC 19.8%); 37.5% had moderate to severe disease activity, 34.3% with extraintestinal manifestations (EIM), 41.6% with an anxious or depressed state and 69.8% had used healthcare resources in the prior 12 months. Moreover, 71.2% used two substances, while 27.3% used three substances. In the total cohort, EIM (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14‐3.34, P  = 0.019) and antidepressant or anxiolytic use (OR 2.51, 95% CI 1.45‐4.39, P   〈  0.001) were positively associated with PSU on multivariate analysis. PSU was associated with increased rate of IBD‐associated imaging (57.6% vs 47.0%, P   〈  0.05). Conclusions PSU is common in IBD. EIM, antidepressant and/or anxiolytic use and imaging studies were independently associated with PSU. This study reinforces the importance of screening patients with IBD for substance use, particularly those with EIM and using antidepressants and/or anxiolytics.
    Type of Medium: Online Resource
    ISSN: 1751-2972 , 1751-2980
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2317117-0
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  • 10
    In: Virology, Elsevier BV, Vol. 389, No. 1-2 ( 2009-06), p. 141-148
    Type of Medium: Online Resource
    ISSN: 0042-6822
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 1471925-3
    SSG: 12
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