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71.
72.
73.
Carrier S 《The Canadian journal of urology》2003,10(Z1):12-16
The phosphodiesterase enzymes, of at least 11 types, are ubiquitous throughout the body, and perform a variety of functions. Phosphodiesterase type 5 (PDE5) is the predominant enzyme in the corpus cavernosum, and plays a crucial role in penile erection. Inhibitors of PDE5 are the most effective oral agents in the treatment of erectile dysfunction. Sildenafil, tadalafil, and vardenafil are all potent inhibitors of PDE5 and show the same mechanism of action, although they have some pharmacological differences that may translate into varying clinical effects. 相似文献
74.
J. Serge LeBel M.D. Dr. Sharad D. Deodhar M.D. Ph.D. Charles H. Brown M.D. 《Diseases of the colon and rectum》1972,15(2):111-115
Conclusions Using basically the same reagents and methodology, we have tried to duplicate the optimistic results of Goldet al. Of 578 samples submitted, 393 met the criteria for the study; results for these 393 are presented. Our results indicate
that CEA can be detected not only in a smaller proportion of gastrointestinal malignancies than that found by Gold and associates,
but also in a similar proportion of inflammatory bowel diseases. Furthermore, we found a significant number of positive in
nongastrointestinal malignancies, as well as chronic inflammatory diseases and collagenoses. Therefore, we feel that the assay,
in its present form, has limited value as a diagnostic tool in the detection of gastrointestinal malignancies. Better purification
procedures, less sensitive methods of detection, or an entirely new approach may produce results of more clinical value than
those we have obtained.
Symposium presented at the meeting of the American Proctologic Society Las Vegas, Nevada, May 10 to 13, 1971.
Presented in part at The Southern Medical Association Meeting, Dallas, Texas, November 16, 1970.
Supported in part by grants from the American Cancer Society, Ohio Division, The Randall Foundation, and a donation from Mr.
F. Ball. 相似文献
75.
beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release probability and presynaptic inhibition by opioids 下载免费PDF全文
Bradaïa A Berton F Ferrari S Lüscher C 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(8):3034-3039
Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions such as morphine. Surprisingly, however, the acute analgesic effect of morphine is enhanced in the absence of beta-arrestin2. To resolve this paradox, we examined the effects of morphine and fentanyl in acute brain slices of the locus coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We report that, in these mice, presynaptic inhibition of evoked inhibitory postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+) (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of miniature inhibitory postsynaptic currents was increased in beta-arrestin2 knockout mice, indicating a higher release probability compared to WT mice. The increased release probability resulted from increased cAMP levels because of impaired phosphodiesterase 4 function and conferred an enhanced efficacy of morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic inhibition by opioids independent of mu-opioid receptor-driven recruitment, which may make beta-arrestin2 a promising target for regulating analgesia. 相似文献
76.
Barold SS 《The American journal of geriatric cardiology》1993,2(6):12-29
Most pacemaker recipients are elderly, and advanced age does not constitute a contraindication to the implantation of a permanent pacemaker. However, pacing in the older patient should no longer be regarded simply as a way to prevent Stokes-Adams attacks or life-threatening bradyarrhythmia. A VVI pacemaker for everyone is now inappropriate, especially in active and otherwise healthy older patients. Selection of the optimal devise or pacing mode in older patients requires an understanding of how aging affects the cardiovascular system (left ventricular diastolic dysfunction) and the natural history of disease, especially sick sinus syndrome after pacemaker implantation. Many retrospective and nonrandomized studies focusing mostly on the sick sinus syndrome have indicated that atrial-based pacing improves the quality and duration of life when compared to single lead ventricle pacing. The lower incidence of chronic atrial fibrillation in patients with atrial-based pacemakers compared to VVI devices is of great importance in the elderly, in whom this arrhythmia is associated with greater morbidity and mortality than in younger individuals. The decreased mortality associated with atrial-based pacing compared to single lead ventricular pacing seems to favor patients older than 70 years. There is now a growing realization that implantation of dual chamber pacemakers in the elderly is cost-effective on a long-term basis by avoiding or reducing the complications associated with single lead ventricular pacing, thereby reducing the need for repeated hospitalizations and medical care. 相似文献
77.
Peter Blanckaert Annelies Cannaert Katleen Van Uytfanghe Fabian Hulpia Eric Deconinck Serge Van Calenbergh Christophe Stove 《Drug testing and analysis》2020,12(4):422-430
This paper reports on the identification and full chemical characterization of isotonitazene (N,N‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using 1H and 13C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (Emax 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder. 相似文献
78.
Zhen Lu Angelica Ortiz Ioannis I. Verginadis Amy R. Peck Farima Zahedi Christina Cho Pengfei Yu Rachel M. DeRita Hongru Zhang Ryan Kubanoff Yunguang Sun Andrew T. Yaspan Elise Krespan Daniel P. Beiting Enrico Radaelli Sandra W. Ryeom J. Alan Diehl Hallgeir Rui Constantinos Koumenis Serge Y. Fuchs 《The Journal of clinical investigation》2021,131(10)
Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects. 相似文献
79.
Martin Sjgrd Vincent Wens Jeroen Van Schependom Lars Costers Marie D'hooghe Miguel D'haeseleer Mark Woolrich Serge Goldman Guy Nagels Xavier De Tige 《Human brain mapping》2021,42(3):626
The pathophysiology of cognitive dysfunction in multiple sclerosis (MS) is still unclear. This magnetoencephalography (MEG) study investigates the impact of MS on brain resting‐state functional connectivity (rsFC) and its relationship to disability and cognitive impairment. We investigated rsFC based on power envelope correlation within and between different frequency bands, in a large cohort of participants consisting of 99 MS patients and 47 healthy subjects. Correlations were investigated between rsFC and outcomes on disability, disease duration and 7 neuropsychological scores within each group, while stringently correcting for multiple comparisons and possible confounding factors. Specific dysconnections correlating with MS‐induced physical disability and disease duration were found within the sensorimotor and language networks, respectively. Global network‐level reductions in within‐ and cross‐network rsFC were observed in the default‐mode network. Healthy subjects and patients significantly differed in their scores on cognitive fatigue and verbal fluency. Healthy subjects and patients showed different correlation patterns between rsFC and cognitive fatigue or verbal fluency, both of which involved a shift in patients from the posterior default‐mode network to the language network. Introducing electrophysiological rsFC in a regression model of verbal fluency and cognitive fatigue in MS patients significantly increased the explained variance compared to a regression limited to structural MRI markers (relative thalamic volume and lesion load). This MEG study demonstrates that MS induces distinct changes in the resting‐state functional brain architecture that relate to disability, disease duration and specific cognitive functioning alterations. It highlights the potential value of electrophysiological intrinsic rsFC for monitoring the cognitive impairment in patients with MS. 相似文献
80.
Lars Costers Jeroen Van Schependom Jorne Laton Johan Baijot Martin Sjgrd Vincent Wens Xavier De Tige Serge Goldman Miguel D'Haeseleer Marie Beatrice D'hooghe Mark Woolrich Guy Nagels 《Human brain mapping》2021,42(5):1376
Working memory (WM) problems are frequently present in people with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a visual‐verbal 2‐back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event‐related fields and theta (4–8 Hz) and alpha (8–13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = .014). This theta power increase value correlated negatively with reaction time on the task in MS (r = −.32, p = .029). Evidence was provided that this relationship could not be explained by a ‘common cause’ confounding relationship with MS‐related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS. 相似文献