Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

Serum-free purified Vero rabies vaccine is safe and immunogenic in children: Results of a randomized phase II pre-exposure prophylaxis regimen study

BackgroundA serum-free, highly purified Vero rabies vaccine (PVRV-NG) has been developed with no animal or human components and low residual DNA content. A phase II randomized clinical study aimed to demonstrate the non-inferiority of the immune response and assess the safety profile of PVRV-NG versus a licensed human diploid cell culture rabies vaccine (HDCV) in a pre-exposure regimen in healthy children and adolescents in the Philippines.MethodologyChildren aged 2–11 years and adolescents aged 12–17 years were randomized (2:1) to receive three injections of either PVRV-NG or HDCV (on day [D] 0, D7 and D28). Rabies virus-neutralizing antibodies (RVNA) were measured at D0, D42 and 6 months after the first injection (month [M] 6). Safety was assessed during the vaccination period and up to 28 days after the last vaccination. Serious adverse events were followed until 6 months after last vaccination.Principal findings342 healthy participants (171 children and 171 adolescents) were randomized and followed for 6 months after the last dose. All participants in both groups had an RVNA titer ≥ 0.5 IU/ml at D42, demonstrating non-inferiority in seroconversion rate for PVRV-NG versus HDCV. Over 90% of participants had RVNA titer ≥ 0.5 IU/ml at M6. PVRV-NG was well tolerated after each vaccination and up to 6 months following the last dose. There were no major safety concerns during the study, and the type and severity of solicited adverse events was similar for both treatment groups.ConclusionsThis study demonstrated the non-inferior immune profile of PVRV-NG compared with HDCV in a pre-exposure setting within a pediatric population. PVRV-NG was well tolerated with no safety concerns. This study is registered at ClinicalTrials.gov (NCT01930357) and EU Clinical Trials Register (2015–003203-30).     

FTY720免疫抑制和抗肿瘤双重作用的研究进展

FTY720是一种来源于冬虫夏草的新型药物,通过诱导淋巴细胞凋亡和归巢而表现出良好的免疫抑制效果。 同时,FTY720还能够诱导肿瘤细胞生长停滞和凋亡,抑制肿瘤的转移。本文综述了FTY720双重作用机制的研究进展。     

MTT法检测极低频弱磁场对SY细胞的影响

本文采用 MTT 示踪法,检测极低频弱磁场对 SY 细胞有无影响。结果发现:频率固定为50Hz 时变化磁场幅值,在150uT、300uT 下细胞吸光度值有明显降低;幅值固定为150uT 时变化磁场频率,在25Hz、50Hz、75Hz 磁场照射下吸光度值均有不同程度下降,而在10Hz、60Hz、100Hz、300Hz、500Hz 磁场照射下没有变化;幅值固定为300uT 时变化磁场频率,在500Hz、75Hz、100Hz、300Hz、磁场照射下吸光度值均有不同程度下降,而在10Hz、25Hz、60Hz、500Hz 磁场照射下没有变化。     

Striatal NPY-Containing Neurons Receive GABAergic Afferents and may also Contain GABA: An Electron Microscopic Study in the Rat

Dual labelling methods were applied to localize simultaneously neuropeptide Y (NPY) and glutamate decarboxylase (GAD) immunoreactivities on ultrathin sections of the rat caudate-putamen (CP). By means of a double peroxidase-anti-peroxidase technique, using 3,3'-diaminobenzidine and benzidine dihydrochloride as chromogens in animals with no colchicine pretreatment, GAD immunoreactivity was found to be present in terminals only whereas NPY immunoreactivity was detected in neurons displaying the features of aspiny type cells and processes. With this approach, we observed numerous synaptic associations of the symmetrical type between GAD-immunoreactive (-Ir) axonal boutons and NPY-Ir cell bodies and dendrites. By combining immunoperoxidase and radioimmunocytochemical labelling in animals pretreated with colchicine, NPY was again detected in a single population of aspiny type neurons whereas GAD immunoreactivity was observed in neurons which could be classified as aspiny and spiny on the basis of their ultrastructural characteristics. All the cells of the aspiny type displaying clear-cut NPY immunoreactivity were also found to be GAD-positive. Some other neurons of both the aspiny and the spiny type were found to be immunoreactive to GAD alone. GAD/NPY dually labelled terminals were also observed and some axo-axonic appositions between GAD- and NPY-Ir terminals were also detected. All in all, these data show that NPY aspiny type neurons of the rat CP receive GABAergic afferents and provide morphological support for two hypotheses: that NPY is co-localized with GABA in some cell bodies, dendrites and axons, and that presynaptic interactions may occur between NPY and GABAergic neuronal systems.     

Distribution of neuropeptide Y in the prosencephalon of man and Cotton-head Tamarin (Saguinus oedipus): colocalization with somatostatin in neurons of striatum and amygdala

Summary The presence, chromatographic properties and localization of neuropeptide Y was demonstrated in postmortem human brain areas of neurologically and neuropsychiatrically normative controls using immunocytochemistry and high performance liquid chromatography combined with radioimmunoassay. NPY-immunoreactivity was found in many regions of the prosencephalon. Numerous perikarya and fibers were present in the neocortex, basal ganglia and limbic-hypothalamic areas. A moderate number of neurons and fibers was observed in the basal forebrain, including the septal complex. A comparative immunohistochemical investigation in perfusion-fixed brains of the old-world ape Saguinus oedipus revealed an almost identical distribution of NPY-immunoreactivity with only minor differences. Colocalization experiments on 1–2 m thin consecutive paraffin sections revealed a large number of NPY neurons throughout the human neostriatum and amygdaloid complex that were also positive for somatostatin. Our findings indicate that detection of neuropeptides in fresh or fixed post-mortem human tissue by different immunochemical methods may actually reflect the in vivo conditions. In addition, the wide distribution of NPY throughout the human brain and its colocalization with other neurotransmitters suggests a physiological role as neuroactive substance, i.e. neuromodulator in the primate central nervous system.     

The renal nerves in the newborn rat

Immunocytochemical methods were used to investigate the distribution of afferent [calcitonin gene-related peptide-(CGRP) immunoreactive and substance P-immunoreactive] nerves and efferent (neuropeptide Y-immunoreactive and dopamine -hydroxylase-immunoreactive) nerves in the kidneys of rats within the 1st day of life. The newborn rat kidney possesses an afferent and efferent innervation. Both afferent and efferent nerves reach the kidney in the same bundles. The afferent sensory fibers predominate overwhelmingly in the renal pelvis and ureter while the efferent fibers clearly predominate in the vasculature. The corticomedullary connective tissue contains both types of innervation with a more prominent afferent innervation (CGRP immunoreactive). Only afferent arterioles of perihilar nephrons were innervated by efferent sympathetic fibers. The distribution and extent of afferent and efferent innervation is consistent with the renal nerves playing a significant role in the transition from fetal to newborn life. The close proximity between afferent and efferent fibers suggests a possible interaction between the two systems.     

显脉香茶菜化学成分的研究

在继续对显脉香茶菜Ｒａｂｄｏｓｉａ ｎｅｒｖｏｓａ （Ｈｅｍｓｌ）Ｃ．Ｙ．Ｗｕ ｅｔ Ｈ．Ｗ．Ｌｉ茎叶有效成分的研究中,又分得一种新的对映－甲壳杉烷型二萜,经理化常数和波谱分析,确定其结构为１α、１５β－二羟基－６β－乙氧基－６,７－Ｂ－断裂－对映－贝壳杉－１６－烯－６,２０－环氧－７,２０－内酯,命名为显脉香茶菜丙素（ｒａｂｄｏｎｅｒｖｏｓｉｎＣ）。