乌司他丁对缺氧缺血性新生鼠的脑保护作用

目的探讨乌司他丁对新生鼠缺氧缺血性脑损伤(HIBD)的作用。方法选7日龄新生Wistar大鼠60只制备HIBD模型。乌司他丁治疗组大鼠分别于术后即刻、术后8、16h腹腔注射乌司他丁一次,术后24h处死。取脑组织迅速秤重,固定,切片行HE和TUNEL染色,测定凋亡细胞数,对皮层脑细胞变性坏死和胶质细胞增生行病理量化评分,电镜观察海马区细胞形态。结果治疗组在脑重增加值及左、右脑重差值、凋亡细胞数和病理量化评分明显低于缺氧缺血组(P<0·01);各治疗组之间比较上述指标无统计学意义(P>0·05)。结论乌司他丁可减轻缺氧缺血后脑细胞水肿、变性、坏死及凋亡,对新生鼠HIBD具有保护作用。     

硫酸镁减轻新生鼠缺氧缺血性脑损伤的实验研究

新生鼠发生缺氧缺血性脑损伤（HIBD）　后可出现神经细胞变性、坏死,还可诱发神经　细胞凋亡。采用原位末端标记技术（TUNEL　染色）可以检测发生凋亡的细胞核DNA片　段。已有资料报告在缺氧缺血性损伤后使用　硫酸镁可减轻大脑细胞损伤。本实验利用新　生鼠HIBD模型,观察硫酸镁预处理对新生　鼠神经细胞的保护作用。 材料和方法 　 实验对象为7日龄Wistar大鼠60只,体重12.5～17.0g,雌雄不限;新生鼠随机分为三组:正常对照组、缺氧缺血损伤组、硫酸镁     

地塞米松对脑缺氧缺血大鼠bid基因表达及细胞凋亡的影响

目的 探讨新生大鼠缺氧缺血性脑损伤（HIBD）后bid基因表达及细胞凋亡的变化，地塞米松（DEX）对其的调控作用，从而阐明DEX预处理对缺氧缺血新生动物神经保护作用的可能机制。方法 7d龄SD大鼠24只。随机分成DEX组、9g／L盐水组（NS组）、HIBD组、健康对照组。DEX和NS组在缺血缺氧前12h腹腔内分别注射DEX、等量NS。通过建立新生大鼠HIBD动物模型，取实验侧大脑半球，采用RT-PCR技术检测脑bid基因表达，采用Tunel法检测凋亡细胞。结果 正常组无bid基因表达，HIBD组bid基因表达明显上调，凋亡细胞数明显增加（P〈0．01）；与HIBD组比较，DEX组bid基因表达明显下调，而凋亡细胞数明显减少（P〈0．01）。结论 脑缺氧缺血引起神经细胞凋亡可能与bid基因表达明显上调有关。DEX能通过下调bid基因表达，从而抑制细胞凋亡，起到神经保护作用。     

神经生长因子对新生大鼠缺氧缺血性脑损伤的保护作用

目的：研究神经生长因子(NGF)对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用。方法：将新生7日龄SD大鼠40只随机分为NGF治疗组(n=16),对照组(n=16)和假手术组(n=8),缺氧缺血(HI)后即刻腹腔注射100 U NGF或等量生理盐水(假手术组不注射),然后观察NGF对HIBD模型鼠的体重增长、脑组织病理及超微结构改变的影响,并用TUNEL法原位标记DNA片段,观察NGF对HIBD后脑细胞凋亡的影响。结果：NGF治疗组体重增长(4.16±0.24) g明显高于对照组(2.86±0.17) g,(P<0.01);TUNEL检测结果,HIBD后24 h治疗组左侧海马和皮质凋亡细胞数(分别为199.75±19.61,182.75±19.12)明显低于对照组(分别为285.50±32.67,271.00±28.36)(P<0.01);HIBD后48 h治疗组左侧海马、皮质凋亡细胞数(分别为77.75±15.76,82.50±19.15)亦明显低于对照组(分别为106.50±16.96,122.75±16.56)(P<0.01)。结论：外源性NGF对HIBD后脑细胞凋亡可能具有一定的保护作用。     

γ-氨酪酸治疗新生大鼠缺氧缺血性脑损伤的实验研究

目的探讨γ-氨酪酸对新生大鼠缺氧缺血性脑损伤（HIBD）的治疗作用。方法采用Rice法制备新生大鼠HIBD模型，用γ-氨酪酸（GABA）灌服HIBD大鼠，用TUNEL法监测大鼠脑组织切片各时间点的细胞凋亡数，用化学方法检测各时间点血清中的超氧化物歧化酶（SOD），一氧化氮（NO），诱生型一氧化氮合酶（iNOS）的浓度。结果（1）缺氧缺血（HI）组各时间点的细胞凋亡率均明显高于假手术对照组；72h时间点的细胞凋亡率最高。（2）GABA治疗组与HI组相比，各时间点的凋亡率均明显降低、SOD值明显升高。（3）发病早期6h时间点HI、GABA两组与正常对照（N）组NO、iNOS浓度比较，差异无统计学意义。两组其余各时间点的NO、iNOS值均明显高于假手术正常对照组，HI、GABA两组比较，GABA各时间点的值均明显低于HI组。结论应用γ-氨酪酸治疗HIBD大鼠，可明显降低HIBD新生大鼠的脑细胞凋亡率。     

腺病毒介导VEGF165基因转移对新生大鼠缺氧缺血性脑损伤的保护作用

目的：研究腺病毒介导的血管内皮生长因子（VEGF）165基因转移对新生大鼠缺氧缺血性脑损伤（HIBD）的神经保护作用。方法：采用细菌内同源重组技术构建Ad-VEGF腺病毒重组载体。7日龄Sprague-Dawley大鼠随机分成4组，假手术组（n=20）、HIBD组（n=25）、病毒缓冲液移植组（Buffer组，n=20），Ad-VEGF移植组（Ad-VEGF组，n=25）。使用Rice法制成HIBD模型，Ad-VEGF移植组和Buffer组在HIBD后3 d于大鼠左侧感觉运动皮层区分别立体定位注射2 μL重组体腺病毒悬液或病毒缓冲液；移植后7 d采用RT-PCR法检测鼠脑VEGF165 mRNA的表达；采用原位缺口末端标记法（TUNEL法）检测鼠脑皮质神经元凋亡情况； 采用免疫组织化学法分别检测VEGF蛋白表达及CD34表达计数大脑皮质微血管密度；30日龄时采用放射型迷宫觅水试验进行行为学测试，35日龄采用苏木精-伊红染色观察鼠脑组织病理学。结果：Ad-VEGF组VEGF165基因表达较HIBD组及Buffer组明显增高（P<0.05）；Ad-VEGF组脑细胞凋亡数目较HIBD组及Buffer组减少(P<0.05)；Ad-VEGF组平均大脑皮质微血管数及VEGF蛋白表达较HIBD组及Buffer组明显增多(P<0.05)； Ad-VEGF组行为学测试成绩较HIBD组及Buffer组改善(P<0.05)； Ad-VEGF组鼠脑皮层神经元变性坏死较HIBD组及Buffer组减轻。结论：腺病毒载体介导的VEGF165基因转移可增加新生鼠脑组织VEGF165 mRNA及VEGF蛋白的表达，减少脑细胞凋亡、增加新生脑血管形成，减轻缺氧缺血性脑损伤，改善远期学习记忆功能。     

硫酸镁对新生鼠缺氧缺血性脑损伤的保护作用

目的　研究硫酸镁预处理对新生鼠缺氧缺血性脑损伤 (HIBD)的保护作用。方法　采用HE和TUNEL染色分别观察正常对照组、缺氧缺血组、硫酸镁预处理组新生鼠大脑神经细胞组织学改变和细胞凋亡情况。结果　硫酸镁预处理组新生鼠大脑组织病变范围和程度较缺氧缺血组减轻 ,且凋亡细胞数量明显减少。结论　硫酸镁预处理可减轻新生鼠HIBD程度 ,具有神经保护作用     

高压氧对新生大鼠缺氧缺血脑损伤模型脑组织神经细胞凋亡及超氧化物歧化酶和脂质过氧化物的影响

目的探讨高压氧（HBO）对新生大鼠缺氧缺血性脑损伤（HIBD）模型脑组织神经细胞凋亡和超氧化物歧化酶（SOD）、脂质过氧化物（MDA）的影响。方法新生7d龄健康SD大鼠随机分为4组：空白对照组（n=68），假手术组（分离左颈总动脉后不结扎直接缝合皮肤，n=66），HIBD组（模型制作采用经典的Rice法，n=60），HBO组（HIBD后行HBO治疗，1h／次／d，最长治疗7d，n=66）。TUNEL试剂盒检测脑组织凋亡的神经细胞，黄嘌呤氧化酶法测定SOD活力（nU／m1）和化学比色法测定MDA含量（μmol／L）。结果（1）缺氧缺血后不同时间HIBD组皮质和海马神经细胞凋亡明显增多，24h达高峰后逐渐下降；HBO组凋亡细胞数较HIBD组明显减少，但仍较空白对照组和假手术组高，差异有统计学意义（P〈0．05）；（2）缺氧缺血后HIBD组SOD含量下降，HBO治疗后SOD的含量较HIBD组升高，且随着治疗时间的延长SOD的水平逐渐升高，24h达高峰，然后逐渐下降，各组比较差异有统计学意义（P〈0．05）；（3）缺氧缺血后HIBD组MDA含量明显升高，18至24h达高峰，随着时间的推移逐渐下降；HBO治疗后MDA含量较HIBD组明显降低，差异有统计学意义（P〈0．05）。结论HBO治疗可减轻HIBD后神经细胞凋亡，机制可能与HBO诱导脑组织SOD的表达，增强组织的抗氧化应激损伤有关。     

高压氧对新生大鼠缺氧缺血性脑损伤的保护作用

为研究高压氧（HBO）对新生儿缺氧缺血性脑损伤（HIBD）的保护作用,应用新生Wistar大鼠制备HIBD模型,将HBO及HBO＋胞二磷胆碱（CDPC）应用于这些模型中,观察它们对HIBD模型鼠的体重增长、病死率、脑病变的影响,并用原位缺口末端标记法（TUNEL）检测HBO对HI后脑细胞凋亡的影响。结果表明：CDPC及HBO＋CDPC治疗后减轻了病死率及脑病变率;并使HIBD模型鼠体重增长快于未治疗组,但两治疗组间差异不显著;HBO治疗组未明显减轻死亡率及脑病变率,也未明显减轻脑细胞凋亡;CDPC及HBO＋CDPC却明显减轻了脑细胞的凋亡（P＜0．001）,但两组间差异不显著。因此提示,HBO对HIBD的保护作用尚待定论。     

缺氧缺血性脑损伤新生大鼠核因子κB表达与脑细胞凋亡的关系

目的观察核因子κB（NF—κB）在缺氧缺血性脑损伤（HIBD）新生大鼠脑细胞凋亡中的表达，探讨其HIBD后NF—κB与细胞凋亡的关系。方法新生7日龄SD大鼠48只，随机分为2组：假手术组和缺氧缺血（HI）模型组，各24只。HI组大鼠采用Rice方法建立新生大鼠HIBD模型，分别于手术后6、24、48、72h取脑组织切片，用免疫组织化学方法检测NF—κB在海马区的表达、TUNEL方法检测神经细胞凋亡。假手术组不作缺氧缺血处理，采用同样方法检测NF—κB。结果假手术组海马区有少量NF—κB表达，且有少量凋亡细胞，各时间点无明显变化（Pa〉0．05）；HI组NF—κB的表达在6h后开始增加，48h达高峰，并持续至72h（P〈0．05），与假手术组相比较差异有统计学意义（Pa〈0．05）；细胞凋亡在6h即开始增加，在24、48、72h逐渐增加，随时间变化差异有统计学意义（Pa〈0．05），与假手术组相比差异有统计学意义（Pa〈0．05）；直线相关回归分析HI组NF—κB表达与细胞凋亡呈显著正相关（各时点的r=0.478，0.552，0.641，0.627 Pa〈005．缩诊HTBn后NF—κB在海马区的持续活化对促进神经细胞凋亡起重要作用。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

Understanding infant formula

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.