Impact of Transplantation Timing on Renal Graft Survival Outcomes and Perioperative Complications.

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT'AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation's impact (8:00 p.m.-8:00 a.m.) versus daytime (8:00 a.m.-8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors' rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.

[Feasibility of chorionic villous sampling outside a prenatal diagnosis center]. / Faisabilité de la biopsie de trophoblaste en maternité de niveau 2 hors centre de référence de diagnostic prénatal.

OBJECTIVES: According to new recommendations, a high combined risk for Down syndrome in the first trimester of pregnancy must indicate the need for a prenatal diagnosis. This is possible thanks to chorionic villous sampling. The objective of our study was to show that chorionic villous sampling is achievable in everyday practice, even outside research centers for pre-natal diagnosis. PATIENTS AND METHODS: It was a descriptive, retrospective study. All the patients who underwent a chorionic villous sampling in our level II maternity center from November 2005 to September 2009 were included. Success and complications rates linked with the procedure were calculated. RESULTS: One hundred and fourteen pregnancies were included. A definitive diagnosis was given in 98.25% of cases. A secondary amniocentesis was necessary in 1.75% of cases. A medical termination of the pregnancy was done in 18.42% of cases. Without accounting for underlying pathology, fetal loss rate was up to 5.75%. Only one case of unexpected fetal loss was noted (1.15% of the ongoing pregnancies). CONCLUSION: Our study shows that the presence of trained professional allows for onsite performance chorionic villous sampling.

Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis.

Resistance to stress-induced apoptosis was examined in cells in which the expression of hsp70 was either constitutively elevated or inducible by a tetracycline-regulated transactivator. Heat-induced apoptosis was blocked in hsp70-expressing cells, and this was associated with reduced cleavage of the common death substrate protein poly(ADP-ribose) polymerase (PARP). Heat-induced cell death was correlated with the activation of the stress-activated protein kinase SAPK/JNK (c-Jun N-terminal kinase). Activation of SAPK/JNK was strongly inhibited in cells in which hsp70 was induced to a high level, indicating that hsp70 is able to block apoptosis by inhibiting signaling events upstream of SAPK/JNK activation. In contrast, SAPK/JNK activation was not inhibited by heat shock in cells with constitutively elevated levels of hsp70. Cells that constitutively overexpress hsp70 resist apoptosis induced by ceramide, a lipid signaling molecule that is generated by apoptosis-inducing treatments and is linked to SAPK/JNK activation. Similar to heat stress, resistance to ceramide-induced apoptosis occurs in spite of strong SAPK/JNK activation. Therefore, hsp70 is also able to inhibit apoptosis at some point downstream of SAPK/JNK activation. Since PARP cleavage is prevented in both cell lines, these results suggest that hsp70 is able to prevent the effector steps of apoptotic cell death. Processing of the CED-3-related protease caspase-3 (CPP32/Yama/apopain) is inhibited in hsp70-expressing cells; however, the activity of the mature enzyme is not affected by hsp70 in vitro. Caspase processing may represent a critical heat-sensitive target leading to cell death that is inhibited by the chaperoning function of hsp70. The inhibition of SAPK/JNK signaling and apoptotic protease effector steps by hsp70 likely contributes to the resistance to stress-induced apoptosis seen in transiently induced thermotolerance.

Quantification of ketotifen and its metabolites in human plasma by gas chromatography mass spectrometry.

Gas chromatography mass spectrometry with selected ion monitoring has been used to develop a method for the quantification of ketotifen and its demethylated, 10-hydroxy and 10-hydroxy demethylated metabolites in human plasma. The minimum detectable concentrations for ketotifen and its demethylated metabolites were 50 pg ml-1 and 300 pg ml-1 for the 10-hydroxy metabolite. The methodology has been applied in studies of the kinetics of the drug in man, and plasma levels of the unchanged drugs and its metabolites in free and conjugated form are reported.

Determination of 3-hydroxy-guanfacine in biological fluids by electron-capture gas-liquid chromatography.

An electron-capture gas-liquid chromatographic method was developed for measuring 3-hydroxy-guanfacine, the main metabolite of guanfacine in human plasma and urine. After extraction, the metabolite was derivatized by condensing the amidino group with hexafluoroacetylacetone and by methylating the NH and OH groups with methyl iodide. The obtained derivative possessed good bioanalytical gas chromatographic properties, using a capillary column. The O-glucuronide was measured after enzymatic hydrolysis. Unchanged guanfacine could be determined in urine together with its 3-hydroxy metabolite by this method.