[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study

The authors describe 12 pregnancies in women with epilepsy using lamotrigine (LTG) monotherapy. A seizure increase in nine pregnancies was probably related to a gradual decline of LTG level-to-dose ratio to 40% of baseline. After delivery, LTG kinetics returned swiftly to baseline, causing toxic side effects in some women. Frequent LTG level monitoring and appropriate dose adjustments are advised in the period before and during pregnancy and after delivery, especially in women on LTG monotherapy.     

1141154113Expression of natural cytotoxicity receptors in peripheral blood NK cell subsets of women with recurrent spontaneous abortions (RSA) or implantation failures

Aim:  To determine if IgA is required for protection against Chlamydia infection in the male reproductive tract (MRT).
Materials and Methods:  Male polyimmunoglobulin receptor knockout mice (PIgR^-/-) and wild-type C57BL/6 (WT) mice were immunised intranasally with chlamydial major outer membrane protein (MOMP) and cholera toxin (CT). MOMP-specific IgG and IgA in serum and prostatic fluids were measured by ELISA. Serum and PF were also assayed for inhibition of in vitro chlamydial infection. Immunized WT and PIgR^-/- mice were challenged by direct inoculation of C. muridarum into the meatus urethra. Four weeks post challenge Chlamydia levels in the penile urethra, epididymis and testis were determined by PCR.
Results:  Equivalent levels of IgG were found in the serum of both WT and PIgR^-/- mice however IgA in serum of PIgR^-/- mice was 19- to 20-fold higher than in WT animals consistent with the lack of the PIgR IgA transport molecule. IgA levels were significantly lower in PIgR^-/- PF compared to WT PF after both immunization and infection. Only PF from WT but not PIgR^-/- animals was able to inhibit in vitro chlamydial infection. Following challenge significantly higher levels of Chlamydia were recovered from the MRT of PIgR^-/- mice compared to WT animals.
Conclusions:  Male mice lacking a functional PIgR were unable to clear a genital tract Chlamydia infection despite high levels of serum IgA. These data show that mucosal IgA plays a major role in preventing chlamydial infection of the male genital tract and suggest that immunization strategies to protect males should target a strong mucosal IgA response.     

人骨髓间充质干细胞分离培养及血管内皮生长因子对其产生的诱导分化作用

目的：目前有关骨髓间充质干细胞向内皮细胞诱导分化的研究较少。本实验分离和培养人骨髓间充质干细胞，用带有VEGF165的质粒转染人骨髓间充质干细胞，探讨血管内皮生长因子对其体外诱导分化的作用。 方法：实验于2005—04／2006—04在吉林大学人兽共患病教育部重点实验室完成。取成人的已排除血液系统肿瘤疾病的新鲜骨髓（自愿提供），采用Percoll梯度分离培养骨髓间充质干细胞，于倒置显微镜下观察细胞形态变化和生长情况。原代细胞培养至增殖接近融合状态时，单克隆培养法分离传代培养，扩增骨髓间充质干细胞。采用流式细胞术检测细胞免疫学表型。在原核细胞大肠杆菌DH5α中复制扩增和提取，纯化、克隆pcDNA3．0-VEGF165质粒。用脂质体转染法转染骨髓间充质干细胞：应用流式细胞术检测诱导后骨髓间充质干细胞免疫学表型变化j并采用免疫荧光染色鉴定转染情况，并设质粒空载和未转染的骨髓间充质干细胞为对照。 结果：人骨髓间充质干细胞原代培养1周后，造血细胞消失，贴壁细胞体积增大，呈现梭形外观，有粗大的细胞突起伸出。2周后细胞融合成单层，梭形突起变长，排列有明显的方向性，细胞排列成旋涡状、网状、辐射状。流式细胞术显示，人骨髓间充质干细胞免疫学表型CD44、CD29阳性，CD34、CD31、CD45阴性。VEGF165诱导骨髓间充质千细胞后CD44表达明显降低，CD31明显升高。免疫荧光染色显示，用FITC标记后的VEGF抗体使细胞显现绿色荧光，用cy3标记的CD31抗体使细胞显现了红色荧光。 结论：转染后的骨髓间充质干细胞细胞表型发生明显转变，CD31表达率明显增高，呈现典型的内皮细胞的表型特征，这说明骨髓间充质干细胞具有向内皮细胞分化的潜能。     

Mid-term clinical and haemodynamic results after aortic valve replacement with the Trifecta bioprosthesis

 Open in a separate windowOBJECTIVESThe aim of this study was to evaluate the clinical and haemodynamic results after implantation of the Trifecta bioprosthesis.METHODSThis study is a retrospective analysis of all patients undergoing Trifecta aortic valve replacement between 01 January 2012 and 31 December 2017 at the Ghent University Hospital. Univariable and multivariable analyses were performed to identify predictors of valve- and procedure-related complications and mortality. The haemodynamic performance was analysed by longitudinal Doppler echocardiography.RESULTSThe mean age of the 182 patients was 77 [standard deviation (SD): 5.5] years; 54.9% were women. The mean follow-up was 39.8 (SD: 24.3) months. Overall survival at 1 and 5 years was 86% (SD: 3%) and 68% (SD: 4%), respectively, and overall freedom from structural valve deterioration was 100% and 98% at 1 and 5 years, respectively. There was no valve thrombosis nor early endocarditis. Urgent surgery was the only risk factor for early mortality in the multivariable analysis [P = 0.009, odds ratio 0.06, 95% confidence interval (CI) 0.01–0.5]. Preoperative atrial fibrillation was the most important predictor of late mortality (P = 0.001, hazard ratio 3.68, 95% CI 1.65–8.21). The average peak gradients were stable from discharge up to 1 and 5 years postoperatively [15 (SD: 6) and 17 (SD: 8) mmHg].CONCLUSIONSThese results confirm the excellent clinical performance of the Trifecta valve, particularly in an elderly age group. Through the 7-year follow-up period, low transvalvular gradients persisted, and only a few patients needed reoperation. Although structural valve degeneration occurred rarely, it was unrelated to valve size or age at implantation; therefore, further long-term follow-up remains mandatory.     

Ring chromosome 20 epilepsy syndrome in children: electroclinical features

Ring chromosome 20 mosaicism is associated with dysmorphic features, mental retardation, and intractable seizures, including recurrent episodes of nonconvulsive status epilepticus. The authors' findings in four children, all without dysmorphic features, indicate that mental deterioration and frequent subtle nocturnal frontal lobe seizures, associated with a characteristic EEG pattern, represent prominent additional clinical features not previously described in this syndrome. This emphasizes the importance of full-night video-EEG in children with frontal lobe seizures and cognitive deterioration.