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  • 1
    Online Resource
    Online Resource
    Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
    Elsevier BV ; 2023
    In:  The Lancet Diabetes & Endocrinology Vol. 11, No. 12 ( 2023-12), p. 905-914
    Details
    In: The Lancet Diabetes & Endocrinology, Elsevier BV, Vol. 11, No. 12 ( 2023-12), p. 905-914
    Type of Medium: Online Resource
    ISSN: 2213-8587
    URL: Article
    DOI: 10.1016/S2213-8587(23)00253-X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-08-17)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-08-17)
    Abstract: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis -regulatory elements as contributing mechanisms to ICP susceptibility.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-29931-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 3
    Online Resource
    Online Resource
    Intramuscular accumulation of prostaglandins during static contraction of the cat triceps surae
    American Physiological Society ; 1991
    In:  Journal of Applied Physiology Vol. 71, No. 5 ( 1991-11-01), p. 1837-1842
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 71, No. 5 ( 1991-11-01), p. 1837-1842
    Abstract: We previously demonstrated that muscle afferent endings are sensitized by exogenous prostaglandins during static contraction of skeletal muscle. The purpose of this study was to determine whether 30 s of static hindlimb contraction, induced by electrical stimulation of the cat sciatic nerve, increases the concentration of immunoreactive prostaglandin E2 (iPGE2) and 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2) in muscle tissue. In addition, the role of ischemia in augmenting prostanoid production was examined. Gastrocnemius muscle was obtained by freeze-clamping tissue, and prostaglandins were extracted from muscle homogenates and measured by radioimmunoassay. Compared with precontraction values, high-intensity (68% of maximal tension) static contraction elevated gastrocnemius iPGE2 and i6-keto-PGF1 alpha by 45 and 53%, respectively (P less than 0.01). Likewise, when blood flow to the gastrocnemius was attenuated by arterial occlusion during and 2 min before low-intensity contraction (29% maximal tension), the intramuscular iPGE2 concentration was increased by 71% (P less than 0.01). Conversely, low-intensity contraction (30% of maximal tension) and arterial occlusion without contraction did not alter the concentration of either prostanoid. Our findings demonstrate that prostaglandins accumulate in muscle during static contraction. We believe that local muscle ischemia may provide a stimulus for this phenomenon. These prostaglandins therefore are available to sensitize afferent endings responsible for reflex adjustments during static muscle contraction.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/jappl.1991.71.5.1837
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1991
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    Development of coronary collateral circulation in left circumflex Ameroid-occluded swine myocardium
    American Physiological Society ; 1987
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 253, No. 5 ( 1987-11-01), p. H1279-H1288
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 253, No. 5 ( 1987-11-01), p. H1279-H1288
    Abstract: Coronary collateral development was examined in 34 pigs after gradual occlusion of the left circumflex coronary artery (LCX) with an Ameroid constrictor. Collateral development was assessed by measurements of myocardial blood flow and regional myocardial function at rest and during exercise over a 16-wk period after placement of the constrictor. Coronary collateral development was adequate to prevent severe infarction and restore blood flow to the collateral-dependent LCX region within 3-7 wk. Infarction averaged 5.0 +/- 1.3% of the LCX region. Blood flows at rest were 1.05 +/- 0.14 and 1.13 +/- 0.15 ml.min-1.g-1 in the subendocardium of the collateral and control regions, respectively, 7 wk postoperatively. Concurrently, collateral vessel development supported normal myocardial function at rest as determined by systolic wall thickening in the LCX region. However, collateral development was limited, since blood flows during moderate and severe exercise were reduced in the LCX region compared with control and left anterior descending and right coronary regions. Blood flow ratios (collateral/control flow) during severe exercise 3 wk postoperatively were 0.23 +/- 0.03 and 0.57 +/- 0.05 in the subendocardium and subepicardium and were constant throughout the 16-wk period throughout the study. Myocardial function of the collateral region also was reduced during exercise and a 30-min recovery period. We suggest that this limited coronary collateral circulation, which develops in response to gradual coronary occlusion in swine, serves as a model for the human collateral circulation for the study of protocols to alter growth and development of coronary collateral vessels.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.1987.253.5.H1279
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1987
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Total plasma creatinine: an accurate measure of total striated muscle mass
    American Physiological Society ; 1981
    In:  Journal of Applied Physiology Vol. 51, No. 3 ( 1981-09-01), p. 762-766
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 51, No. 3 ( 1981-09-01), p. 762-766
    Abstract: Creatinine is a metabolite unique to striated muscle. Measurement of 24-h urinary creatinine excretion is an established method for estimating striated muscle mass. However, accurate assessment of urinary creatinine excretion is often impractical. We investigated the hypothesis that total plasma creatinine could be used instead of urinary creatinine excretion to estimate body composition. In 24 men, plasma volume and plasma creatinine concentration were measured, and total plasma creatinine was calculated as the product of these two measurements. Other measurements included urinary creatinine excretion, total body water, and anthropometry. Total plasma creatinine correlated strongly with urinary creatinine excretion (r = 0.82) and with weight, total body water, and anthropometrically estimated lean body mass. Muscle mass could be predicted by the equation: 0.88 x total plasma creatinine (mg). To verify this relationship, total plasma creatinine was prospectively measured in four dogs, then their total striated muscle was removed and weighed. Predicted muscle mass was within +/- 3.9% (range = 0.5–10.8%) of observed muscle mass. The ability to estimate muscle mass conveniently and accurately from total plasma creatinine should prove valuable for future studies in physiology and body composition.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/jappl.1981.51.3.762
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1981
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 6
    Online Resource
    Online Resource
    Training effects on regional blood flow response to maximal exercise in foxhounds
    American Physiological Society ; 1987
    In:  Journal of Applied Physiology Vol. 62, No. 4 ( 1987-04-01), p. 1724-1732
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 62, No. 4 ( 1987-04-01), p. 1724-1732
    Abstract: The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8–12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/jappl.1987.62.4.1724
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1987
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 7
    Online Resource
    Online Resource
    Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine
    American Physiological Society ; 1992
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 262, No. 1 ( 1992-01-01), p. R112-R119
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 262, No. 1 ( 1992-01-01), p. R112-R119
    Abstract: Both histamine and bradykinin induce gastric-cardiovascular reflexes and are released during several pathophysiological conditions. This study examined the possibility that histamine modulates the magnitude of the reflex response to stimulation by bradykinin. Thus in chloralose anesthetized cats, the cardiovascular response to stimulation of the gastric serosa with 1 microgram/ml bradykinin was monitored before and after topical application of 100 micrograms/ml histamine (n = 6) or 1 mg/ml diphenhydramine (H1-receptor antagonist) and histamine (n = 5). After application of histamine, bradykinin-induced increases in mean arterial pressure and left ventricular pressure were attenuated by 23 and 27%, respectively. Conversely, when the H1-receptors on the serosal surface of the stomach were blocked (n = 5) before application of histamine, the pressor response to bradykinin was augmented by 26%. To determine the afferents that might contribute to the attenuating effect of histamine, we recorded single unit activity in 14 A delta and 21 C visceral afferent fibers in response to bradykinin stimulation before and after histamine stimulation. We observed that the impulse activity of 10 of the A delta and 14 of the C fibers to bradykinin stimulation was reduced after treatment with histamine. These results suggest that histamine induces an inhibitory effect on the nerve endings of visceral A delta and C fibers to the action of bradykinin through an H1-receptor mechanism. This inhibitory effect attenuates the magnitude of the consequent cardiovascular reflex response.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.1992.262.1.R112
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1992
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    RECEPTOR-MEDIATED CORONARY ARTERY CONSTRICTION AFTER ISCHEMIA: INFLUENCE OF EXERCISE TRAINING.
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Medicine & Science in Sports & Exercise Vol. 31, No. Supplement ( 1999-05), p. S227-
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. Supplement ( 1999-05), p. S227-
    Type of Medium: Online Resource
    ISSN: 0195-9131
    URL: Article
    DOI: 10.1097/00005768-199905001-01070
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 9
    Online Resource
    Online Resource
    Cardiovascular reflexes evoked by histamine stimulation of the stomach
    American Physiological Society ; 1991
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 260, No. 4 ( 1991-04-01), p. H1098-H1105
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 260, No. 4 ( 1991-04-01), p. H1098-H1105
    Abstract: This study examined the potential for histamine to cause cardiovascular reflexes when applied to the serosal or mucosal surface of the stomach. Thus, in chloralose-anesthetized cats, histamine was applied to the serosal surface of the stomach in concentrations ranging from 0.5 to 1,000 micrograms/ml. This resulted in graded increases in mean arterial pressure (MAP), maximal left ventricular pressure over time (dP/dt), and heart rate ranging from 9 +/- 4 to 30 +/- 3 mmHg, 450 +/- 103 to 1,710 +/- 610 mmHg/s, and 2 +/- 1 to 13 +/- 4 beats/min, respectively. Histamine stimulation of the gastric serosa evoked a greater pressor response than that observed when the same concentration of histamine (100 micrograms/ml) was applied to the gastric mucosa (43 +/- 7 vs. 13 +/- 3 mmHg, respectively). In six cats, celiac ganglionectomy abolished the previously observed cardiovascular response to histamine stimulation of the serosal surface of the stomach. When the gastric serosa was treated with the H1-receptor antagonist diphenhydramine (1 mg/ml) (n = 5), the cardiovascular response to histamine was abolished. In five other cats, administration of the H2-antagonist ranitidine (1 mg/ml) had no effect on the histamine-induced responses. When indomethacin (2-5 mg/ml), was applied to the serosal surface of the stomach (n = 6), histamine-induced increases in MAP and dP/dt were attenuated. However, application of PGE2 (1 microgram/ml) restored these two responses. These results suggest that histamine stimulates H1-receptors in the gastric wall to cause reflex cardiovascular responses that are dependent, in part, on the local production of prostaglandins.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.1991.260.4.H1098
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1991
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Role of spinal NMDA and non-NMDA receptors in the pressor reflex response to abdominal ischemia
    American Physiological Society ; 2002
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 282, No. 3 ( 2002-03-01), p. R850-R857
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 282, No. 3 ( 2002-03-01), p. R850-R857
    Abstract: Abdominal ischemia induces a pressor reflex caused mainly by C-fiber afferent stimulation. Because excitatory amino acids, such as glutamate, bind to N-methyl-d-aspartate (NMDA) and non-NMDA [ dl-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)] receptors and serve as important spinal neurotransmitters, we hypothesized that both receptors play a role in the abdominal ischemia pressor reflex. In chloralose-anesthetized cats, NMDA receptor blockade with 25.0 mM dl-2-amino-5-phosphonopentanoate did not alter the pressor reflex (33 ± 9 to 33 ± 7 mmHg, P 〉 0.05, n = 4), whereas AMPA receptor blockade with 4.0 mM 6-nitro-7-sulfamylbenzo( f)quinoxaline-2,3-dione significantly attenuated the reflex (29 ± 5 to 16 ± 4 mmHg, P 〈 0.05, n = 6). Because several studies suggest that anesthesia masks the effects of glutamatergic receptors, this experiment was repeated on decerebrate cats, and in this group, NMDA receptor blockade with 25.0 mM dl-2-amino-5-phosphonopentanoate significantly altered the pressor reflex (36 ± 3 to 25 ± 4 mmHg, P 〈 0.05, n = 5). Our combined data suggest that spinal NMDA and AMPA receptors play a role in the abdominal ischemia pressor reflex.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.00297.2001
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2002
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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