Effects of propofol sedation on BDNF-TrkB/p75 signal and cognitive function in rat hippocampus / 上海交通大学学报（医学版）

Objective·To detect the effects of propofol sedation on cognitive function in rats and its mechanism. Methods?·?Forty-eight SD rats were randomly divided into three groups, i.e. control group, 100?mg/kg group and 300?mg/kg group. Rats were administrated intraperitoneally with propofol (10?mg/mL, 100?mg/kg or 300?mg/kg). The mRNA levels of brain derived neurotropic factor (BDNF)-TrkB/p75 signal molecules in rat hippocampus were evaluated by realtime PCR 45 min after propofol treatment. Learning and memory ability was examined by inhibitory avoidance (IA) test after propofol treatment. Results?·?The mRNA levels of BDNF in the hippocampal tissue were (1.20±0.13) fold (P=0.002) and (88±12) % (P=0.044) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group after injection of propofol. The mRNA levels of TrkB were (1.01±0.11) fold ( P=0.982) and (86±11) % (P=0.018) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. The mRNA levels of p75 were (1.02±0.10) fold (P=0.778) and (1.59±0.18) fold (P=0.000) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. There was no significant difference of the 24 h IA memory retention latency between 100?mg/kg group and control group. The 24 h IA memory retention latency in 300?mg/kg group was significantly decreased compared with control group (P=0.028) and 100?mg/kg group (P=0.020). Conclusion?·?Propofol dose-dependently regulates the expression of BDNF-TrkB/p75 signal molecules, and high dose propofol may reduce cognitive function via BDNF-TrkB/p75 signal.

Propofol activates rat hippocampal astrocytes time-dependently via ERK signaling pathway / 上海交通大学学报（医学版）

Objective·To detect the effects of propofol on rat hippocampal astrocytes and clarify its mechanism.Methods·According to the time after propofol injection,twenty-four SD rats were randomly divided into three groups,i.e.0 min,45 min and 90 min group.Rats were administrated intraperitoneally with propofol (10 mg/mL,100 mg/kg body weight).The levels of glial fibrillary acidic protein (GFAP) and S100β mRNA in rat hippocampus were evaluated by realtime PCR.And cell viabilities and levels of GFAP mRNA were examined in primary cultured hippocampal astrocytes induced by 10 μmol/L propofol with or without 10 μmol/L extracellular signal-regulated kinase (ERK) inhibitor PD98059 pretreatment.Results·The mRNA levels of GFAP in the hippocampal tissue were (1.32±0.12) times (P=0.000) and (1.12±0.09) times (P=0.012) that in 0 min group,respectively,45 min and 90 min after injection of propofol.The mRNA levels of S100β in the hippocampal tissue were (1.14±0.11) times (P=0.005) and (1.05±0.10)times (P=0.284) that in 0 min group,respectively,45 min and 90 min after injection of propofol.The mRNA levels of GFAP and S100β were timedependently altered,first increasing,and then decreasing.In vitro,the cell viabilities (P=0.041) and levels of GFAP mRNA (P=0.026) in primary cultured hippocampal astrocytes were significantly elevated after propofol treatment,and these effects of propofol were reversed by ERK inhibitor PD98059.Conclusion·Propofol time-dependently upregulated the expression of GFAP and S100β via ERK signaling pathway in rat hippocampal astrocytes,so as to activate astrocytes.

Analysis of inborn errors of metabolism: disease spectrum for expanded newborn screening in Hong Kong / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.</p><p><b>METHODS</b>The laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.</p><p><b>RESULTS</b>Among the cohort, 43 patients were diagnosed of IEM, including 30 cases (69%) of amino acidemias (predominantly citrin deficiency, hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type I), 5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8 cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births, or 0.243 cases per 1000 live births. This incidence is similar to those reported worldwide, including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births.</p><p><b>CONCLUSIONS</b>Our data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city, a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.</p>

Molecular basis of von Hippel-Lindau syndrome in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.</p><p><b>METHODS</b>Nine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULTS</b>The nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.</p><p><b>CONCLUSIONS</b>Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.</p>

Phenylketonuria in Hong Kong Chinese: a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China / 中华医学杂志(英文版)

Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15,000 livebirths. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among HongKong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia (95 μmol/L), significantly high phenylalnine-to-tyrosine ratio (3.1), and elevated prolactin of 1109 mIU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1:c.259C>T; NP_000308.1: p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29,542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.