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91.
92.
Mohamad Kassem Ali El Habhab Guillaume Kreutter Lamia Amoura Philippe Baltzinger Malak Abbas Noura Sbat Fatiha Zobairi Valérie B. Schini-Kerth Laurence Kessler Florence Toti 《Transplantation proceedings》2021,53(5):1736-1743
BackgroundIschemia-driven islet isolation procedure is one of the limiting causes of pancreatic islet transplantation. Ischemia-reperfusion process is associated with endothelium dysfunction and the release of pro-senescent microvesicles. We investigated whether pro-senescent endothelial microvesicles prompt islet senescence and dysfunction in vitro.Material and methodsPancreatic islets were isolated from male young rats. Replicative endothelial senescence was induced by serial passaging of primary porcine coronary artery endothelial cells, and microvesicles were isolated either from young passage 1 (P1) or senescent passage 3 (P3) endothelial cells. Islet viability was assessed by fluorescence microscopy, apoptosis by flow cytometry, and Western blot. Function was assessed by insulin secretion and islet senescence markers p53, p21, and p16 by Western blot. Microvesicles were stained by the PKH26 lipid fluorescent probe and their islet integration assessed by microscopy and flow cytometry.ResultsRegardless of the passage, half microvesicles were integrated in target islets after 24 hours incubation. Insulin secretion significantly decreased after treatment by senescent microvesicles (P3: 1.7 ± 0.2 vs untreated islet: 2.7 ± 0.2, P < .05) without altering the islet viability (89.47% ± 1.69 vs 93.15% ± 0.97) and with no significant apoptosis. Senescent microvesicles significantly doubled the expression of p53, p21, and p16 (P < .05), whereas young microvesicles had no significant effect.ConclusionPro-senescent endothelial microvesicles specifically accelerate the senescence of islets and alter their function. These data suggest that islet isolation contributes to endothelial driven islet senescence. 相似文献
93.
94.
Oulimata Dieng MD Valerie Laurence MD Christelle Logerot PhD Youlia M. Kirova MD 《The breast journal》2021,27(10):787-790
Eribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin. 相似文献
95.
Anoop N. Koshy Jefferson Ko Omar Farouque Shamil D. Cooray Hui-Chen Han Benjamin Cailes Paul J. Gow Laurence Weinberg Adam Testro Han S. Lim Andrew W. Teh 《American journal of transplantation》2021,21(2):593-603
Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study. 相似文献
96.
Lucie Matrat MD Mathias Ruiz MD Emmanuelle Ecochard-Dugelay MD Irène Loras-Duclaux MD Stéphanie Marotte MD Sophie Heissat MD Pierre Poinsot MD Anne-Laure Sellier-Leclerc MD Justine Bacchetta MD PhD Laurence Dubourg MD PhD Noël Peretti MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2022,46(1):180-189
97.
98.
Eight elderly patients (mean age +/- SD, 73.2 +/- 9.5 years) were studied with Holter electrocardiographic monitoring for 24 h before and 24 h after an electroconvulsive therapy (ECT) treatment. Patients with a history of cardiac disease but who were not experiencing any active cardiac symptoms were chosen for study. They were not receiving either cardioactive medications or psychotropic agents that can effect cardiac rhythm or conduction. Each patient served as his own control, with direct comparison of the periods before and after the treatment. There were no differences before and after ECT in the electrocardiogram. One minute after the seizure, patients were hypertensive and tachycardic. ECT does not appear to pose additional risk in stable, elderly patients with a history of cardiac disease. 相似文献
99.
Nika Adham Laurence A. Borden Lee E. Schechter Eric L. Gustafson Tamara L. Cochran Pierrre J.-J. Vaysse Richard L. Weinshank Theresa A. Branchek 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(6):566-575
We recently described the cloning of a fifth member of the 5-hydroxytryptamine (5-HT)1 (serotonin1) receptor class that inhibits adenylyl cyclase, namely the human 5-HT1F receptor (Adham et al. 1993 a). In the present study we have examined in greater detail the functional coupling of the 5-HT1F receptor in two different cell lines, NIH-3T3 and LM(tk–) fibroblasts (receptor densities of 1.7 and 4.4 pmol/mg protein, respectively). The maximal inhibitory response elicited by 5-HT was significantly greater in NIH-3T3 as compared to LM(tk–) cells, whereas the EC50 values were comparable.To investigate the relationship between receptor occupancy and inhibition of cAMP accumulation mediated by 5-HT1F receptors in NIH-3T3 cells (and hence the degree of receptor reserve), we used the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The half-maximal response required only about 10% receptor occupancy, consistent with a receptor reserve of 90% (88±2.1%, n = 4) for 5-HT-induced inhibition of FSCA. Despite the presence of such a high degree of receptor reserve, a range of intrinsic activities was displayed by structurally diverse classes of compounds. For example, sumatriptan and lysergol were as efficacious as 5-HT itself and thus acted as full agonists, whereas metergoline and 1-NP behaved as partial agonists and as shown previously (Adham et al. 1993a), methiothepin was a silent antagonist (Kb = 438 nM).We have also investigated activation of additional signal transduction pathways by the 5-HT1F receptor and found that the responses differ in the two cell lines with respect to stimulation of phospholipase C. For example, in NIH-3T3 cells no elevation of inositol phosphates (IP) of [Ca2+]i was observed even at very high agonist concentrations (100 M). In contrast, in LM(tk–) cells concentrations of 5-HT as low as 10 nM induced stimulation of IP and a rapid increase of [Ca2+]i. The 5-HT1F receptor failed to alter arachidonic acid release in either cell line.The maximal increase in IP accumulation in LM(tk–) cells was modest, averaging about 100% above basal. The increases of IP and [Ca2+]i required 5-HT concentrations less than one order of magnitude greater than those inhibiting FSCA (EC50 = 17, 55 and 8 nM, respectively), and both responses were blocked by 100 M methiothepin. All three responses (cAMP, IP, and [Ca2+]i) were sensitive to pertussis toxin pre-treatment, suggesting the involvement of Gi/Go protein(s) in these signal transduction pathways. [Ca2+]i was also elevated by sumatriptan, which may provide a mechanism by which this drug causes constriction of the vasculature. In conclusion, these data indicate that the human 5-HT1F receptor can couple to multiple effectors, and that this coupling is cell-type dependent.Abbreviations FSCA
forskolin-stimulated cAMP accumulation
- [Ca2+]
intracellular free calcium concentration
- AA
arachidonic acid
- EEDQ
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
- CHO
chinese hamster ovary cell
- LM(tk–)
mouse fibroblast cell
- Bmax
maximal binding site density
- Ki
apparent dissociation constant obtained from competition binding studies
- G protein
guanine nucleotide-binding protein
- HBS
HEPES-buffered saline
- IP
inositol phosphates
- IP3
inositol 1,4,5 trisphosphate
- PLC
phospholipase C
- Kb
antagonist dissociation constant
- Kd
equilibrium dissociation constant
- N-1F-6
stable NIH-3T3 cells expressing the cloned 5-HT1F receptor
- L-1F-3
stable LM(tk–) cells expressing the cloned 5-HT1F receptor
- PTX
pertussis toxin
- BSA
bovine serum albumin
- METH
methiothepin
- SUMA
sumatriptan
- 5-MeO-DMT
5-methoxy-N,N-dimethyltryptamine
- 1-NP
1-(1-napthyl)piperazine
- 5-CT
5-carboxyamidotryptamine
Correspondence to: N. Adham at the above address 相似文献
100.
Grummer-Strawn LM Rice SP Dugas K Clark LD Benton-Davis S 《Maternal and child health journal》1997,1(1):35-42
Objective: This study evaluates the effectiveness of a peer counseling program at increasing breastfeeding by participants in the Mississippi Special Supplemental Nutrition Program for Women, Infants and Children (WIC). Methods: Data from the 1989–1993 Pediatric Nutrition Surveillance System were analyzed to compare breastfeeding rates in clinics with and without peer counseling programs. A questionnaire completed by program staff to describe the program in greater detail helped identify characteristics associated with greater success. Results: The incidence of breastfeeding rose from 12.3% to 19.9% in those clinics with peer counseling programs, but only from 9.2% to 10.7% in clinics without a program. Clinics that started a program earlier showed greater changes in breastfeeding incidence. However, the presence of lactation specialists or consultants in the clinic appeared to be more important than the presence of less-trained peer counselors. Peer counselors who spent more than 45 minutes per participant were more effective than those spending less time. Conclusions: The peer counseling program significantly increased the incidence of breastfeeding, particularly in clinics with lactation specialists and consultants. Success can be enhanced by ensuring that peer counselors spend a great deal of time with the participants. 相似文献