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21.
F. Pagani A. Brambilla A. Schiavone A. Giachetti 《Naunyn-Schmiedeberg's archives of pharmacology》1985,329(1):45-49
Summary In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mol/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mol/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mol/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors ( and ) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of prosecretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh. 相似文献
22.
B. Wilffert P. N. M. van Heiningen M. J. Mathy A. de Jonge M. J. M. c. Thoolen P. B. M. W. M. Timmermans P. A. van Zwieten 《Naunyn-Schmiedeberg's archives of pharmacology》1984,328(1):76-82
Summary Interactions between the putative calcium entry promotor Bay k 8644 and both -1 and 1-adrenocepter mediated increases in diastolic pressure were studied in the pithed normotensive rat. The 1-adrenocepter mediated pressor responses elicited by B-HT920, TL-99, DP-6,7-ADTN and B-HT958 were potentiated by Bay k 8644, reflected by a leftward shift and an increase in the maximum of the log dose-pressor respinse curves. The -1-adrenocepter effects elicited by cirazoline, methoxamine, (–)-amidephrine, St 587, (–)-phenylephrine and Sgd 101/75 were less enhanced by Bay k 8644. Only a leftward shift of the dose-response curves was observed, which was most pronounced for (–)-phenylephrine and Sgd 101/75. The -1 and 2-adrenocepter pressor components of (–)-noradrenaline were similarly distinguished by Bay k 8644 as observed for the selective -1 or 2-adrenocepter agonists.Effects of Bay k 8644 on the increase in diastolic pressure mediated by B-HT 920, St 587 and cirazoline were also studied after pretreatment with the calcium entry blocker nifedipine. After additional pretreatment with nifedipine the potentiation by Bay k 8644 observed for B-HT 920 and St 587 was more pronounced. The presence of nifedipine had no effect on the interaction between Bay k 8644 and cirazoline.It is concluded that Bay k 8644 behaves as a mirror image of nifedipine. The observation that Bay k 8644 enhances 2-adrenocepter mediated pressor effects more effectively than 1-adrenocepter increases in diastolic pressure is in accordance with the hypothesis of the more pronounced calcium dependency of 2-adrenocepter mediated pressor responses. The data obtained for ceptor mediated pressor responses. The data obtained for St 587 and (–)-phenylephrine are in apparent contradiction to the finding that the pressor responses to the former drug are more markedly inhibited by calcium entry blockade than those of the latter. It is suggested that St 587 employs calcium channels which are already maximally modulated and that (–)-phenylephrine makes use of calcium channels which are in a rather inactive state. The hypothesis is put forward that the intrinsic activity of 2-adrenocepter agonists reflects their ability to bring calcium channels in an active state. 相似文献
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24.
William A. Werbel Sunjae Bae Sile Yu Fawaz Al Ammary Dorry L. Segev Christine M. Durand 《American journal of transplantation》2021,21(2):717-726
Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: 1.081.612.41, P = .04) and over the study period (aHR: 1.021.391.90, P = .03), without difference in death-censored graft failure (aHR 0.600.911.36, P = .33) or mortality (aHR: 0.751.151.77, P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable. 相似文献
25.
Rabea Asleh Hilmi Alnsasra Amir Lerman Alexandros Briasoulis Naveen L. Pereira Brooks S. Edwards Takumi Toya John M. Stulak Alfredo L. Clavell Richard C. Daly Sudhir S. Kushwaha 《American journal of transplantation》2021,21(2):626-635
We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk. 相似文献
26.
Jonathan Kentley Rina Allawh Swati Rao Alden Doyle Amar Ahmad Kumar Nadhan Charlotte Proby Catherine A. Harwood Christina L. Chung 《American journal of transplantation》2021,21(3):1215-1226
Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin. 相似文献
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28.
Christina D. Mejia Adam M. Frank Pooja Singh Anju Yadav 《American journal of transplantation》2021,21(3):1322-1325
Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies against inhibitory receptors on T cells resulting in anticancer activity. In kidney transplant (KT) recipients, ICPI use has been associated with acute allograft rejection. In failed allografts, however, the effects of ICPIs are unknown. We present a case of a 66-year-old man with a history of diabetes, renal cell cancer, left native nephrectomy, and end-stage kidney disease. He received a deceased donor KT which failed after 6 years due to biopsy-proven recurrent diabetic nephrosclerosis. He was started on hemodialysis and his immunosuppression was gradually weaned off. A year later, he was diagnosed with renal cell cancer in his right native kidney requiring nephrectomy. He later developed metastasis and was started on combination ICPIs. He developed hematuria, allograft pain, and malaise consistent with graft intolerance syndrome 28 days after starting ICPIs. Urine culture and cystoscopy were normal. A computed tomography scan of his abdomen revealed an enlarged allograft with patchy enhancement. After a multidisciplinary discussion, he underwent transplant nephrectomy. Histopathology showed chronic active T cell–mediated rejection. As ICPI use becomes prevalent, practitioners need to be aware of its potential complications among KT recipients both with functioning and failed allografts. 相似文献
29.
Benjamin Coiffard Philipp M. Lepper Eloi Prud’Homme Florence Daviet Nadim Cassir Heinrike Wilkens Sami Hraiech Frank Langer Pascal A. Thomas Martine Reynaud-Gaubert Robert Bals Hans-Joachim Schäfers Laurent Papazian Frederik Seiler 《American journal of transplantation》2021,21(4):1586-1596
It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19. 相似文献
30.
Hanno Niess Nikolaus Börner Maximilian Muenchhoff Elham Khatamzas Manfred Stangl Alex Graf Philipp Girl Enrico Georgi Dionysios Koliogiannis Gerald Denk Michael Irlbeck Jens Werner Markus Guba 《American journal of transplantation》2021,21(4):1629-1632
To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA. 相似文献