Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT₁ and MT₂, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT₁ and MT₂. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT₁ and MT₂ by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT₁ or MT₂. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT₂ expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.     

Tyrosinemia type 1 in pediatric nephrology: Not always straightforward

The main clinical features of tyrosinemia type 1 usually appear in the first months of life, including fever, diarrhea, vomiting, liver involvement, growth failure, and renal proximal tubulopathy with subsequent hypophosphatemic rickets. An early diagnosis is crucial in order to provide specific management and to prevent complications. Here, we report on two cases referred primarily to pediatric nephrologists for the diagnosis of “neonatal tubulopathy” and management of “X-linked hypophosphatemia (XLH),” respectively. Our aim is to emphasize that (1) even a mixed tubulopathy can reveal tyrosinemia, and (2) tyrosinemia is a classic differential diagnosis of XLH that should not be forgotten, especially in the era of the anti-FGF23 burosumab.     

宫腹腔镜联合手术诊治不孕症150例分析

目的:探讨宫腹腔镜联合手术在诊治不孕症中的应用。方法:对150例不孕症患者行宫腹腔镜联合手术,对不孕症病因进行诊断,同时行治疗。结果:盆腔粘连和输卵管阻塞是不孕症的主要原因。子宫内膜息肉和正常盆腔占次要比例。子宫内膜异位症和多囊卵巢也是主要病因。150例同时行宫腹腔镜输卵管通液和各种疾病的治疗。联合手术后妊娠率为48.8%。结论:腹腔镜联合手术,在一次麻醉下,可以对不孕的原因全面评价和明确诊断,在诊断同时进行治疗,对不孕症的诊断和治疗有重大的意义,值得推广。     

Acute respiratory distress during Caesarean section under spinal anaesthesia A probable case of anaphylactoid reaction to Syntocinon

A case of life-threatening respiratory distress during a Caesarean section under spinal anaesthesia is reported. Possible causes of the event including anaphylactoid reactions and the methods of their diagnosis are discussed. The most likely cause of the episode was felt to be an anaphylactoid reaction to Syntocinon.     

The Rigiflex TTS: A New Method to Dilate Benign Esophageal Stenosis

Abstract: This paper dicusses the use of esophageal dilatation with a Rigiflex TTS balloon. This method was used 45 times on 11 patients affected by anastomotic or a severe grade peptic esophageal stenosis. Fluoroscopic guidance was used in 36 procedures (80%) without effecting the mean duration of the treatment (12 minutes). The results were considered satisfactory when these goals had been achieved: a) dilatation of the stenosis over 15 mm; b) a dysphagia free-time of more than 6 months. A satisfactory result was achieved in 10 patients (90.9%), without deaths and major complications. 5 patients received 1 dilatation and the other 5 needed, 3-3-4-7–11 procedures respectively to obtain a satisfactory result. On these basis we consider that its great efficacy, security and tolerability depend on the following characteristics of the Rigiflex TTS balloon: 1) “radial” dilatation; 2) the possibility of introducing the balloon through the operative channel of the fiberscope; 3) direct visualization of the stenosis during dilatation. The following disadvantages with this method are: the absence of a tactile sensation of dilatation and the elevated cost of the instrument. We conclude that the Rigiflex TTS balloon is an important alternative to guide-wire techniques, especially for the treatment of severe esophageal strictures.     

妊娠肝内胆汁淤积症患者血清一氧化氮和内皮素的变化及意义

目的：探讨妊娠肝内胆汁淤积症（ICP）患者外周静脉血清、新生儿脐静脉血清中一氧化氮（NO）、内皮素（ET）、丙二醛（MDA）和超氧化物歧化酶（SOD）含量的变化及在ICP发病中的作用。方法：以ICP组28例为研究组，测定其外周静脉血清及新生儿脐静脉血清中的NO、ET、MDA和SOD，以年龄相近的24例正常孕妇作为对照组。结果：ICP患者的MDA和ET含量较正常晚期妊娠显著增高（P＜0．01），ICP患者的NO和SOD含量与对照组相比无显著性差异（P＞0．05）。母血清中NO、ET、MDA含量均较新生儿脐静脉血清中的含量高，差异有显著性（P＜0．01）。结论：妊娠期体内氧化和抗氧化失衡及ET水平的增高可能与ICP的发生、发展有关。