Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

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.     

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

腹腔镜胆囊切除术治疗急性结石性胆囊炎的疗效

目的探讨分析对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗的临床效果,以及对患者的胃肠功能和C反应蛋白所造成的影响。方法本次研究对象乃是我院肝胆外科于2017年4月-2019年4月期间收治的急性结石性胆囊炎患者62例,按照患者就诊的先后顺序对其进行平均分组,比较两组患者的术后肠鸣音恢复时间、肛门排气时间、排便时间、C反应蛋白水平以及并发症发生率。结果腹腔镜手术组患者的术后肠鸣音恢复时间(13.6±3.5)小时、肛门排气时间(16.5±2.7)小时以及排便时间(25.7±3.3)小时,均明显少于开腹式手术组患者(P<0.05);腹腔镜手术组患者的术后并发症发生率(6.45%)明显低于开腹式手术组患者(25.80%)(P<0.05);腹腔镜手术组患者的C反应蛋白水平为(10.4±2.5)mg/L,少于开腹式手术组患者(P<0.05)。结论根据本次研究的结果可以确认,对急性结石性胆囊炎患者采用腹腔镜胆囊切除术进行治疗能够取得更好的效果,可以促使患者的胃肠功能在术后更快的恢复,提高患者的C反应蛋白,从而有效避免患者出现并发症。     

Depression embodied: an ambiguous striving against fading

Although depression is associated to physical discomfort, meanings of the body in depression are rarely addressed in clinical research. Drawing on the concept of the lived body, this study explores depression as an embodied phenomenon. Using a hermeneutic phenomenological approach, the analysis of narrative‐based interviews with 11 depressed adults discloses a thematic structure of an embodied process of an ambiguous striving against fading. Five subthemes elicit different dimensions of this process, interpreted as disabling or enabling: feeling estranged, feeling confined, feeling burdensome, sensing life and seeking belongingness. In relation to clinical practice, we suggest that the interdisciplinary team can focus on enhancing the enabling dimensions, for example through guided physical activities to support the patient to feel more alive, capable and connected. Moreover, we suggest that the treatment process benefits from an increased awareness of the ambiguity in the patient's struggle, acknowledging both destructive and recharging elements of the withdrawing, and the perceived conflict in‐between.     

脑卒中患者急性应激障碍及影响因素研究

目的探讨脑卒中患者急性应激障碍发生现状及影响因素。方法采用斯坦福急性应激反应问卷对349例脑卒中住院患者进行调查。结果共163例(46.70%)患者发生急性应激障碍;Logistic回归分析结果显示,患者性格、是否存在偏瘫及是否吞咽功能障碍是脑卒中患者发生急性应激障碍的主要影响因素(P0.05,P0.01)。结论脑卒中患者急性应激障碍发生率较高,内向性格及存在偏瘫和吞咽功能障碍的患者更容易发生急性应激障碍。医护人员应及时为高危患者提供个体化治疗及预见性护理,防止脑卒中患者发生急性应激障碍。