黄芪甲甙对病毒性心肌炎小鼠神经生长因子表达的影响

目的探讨黄芪活性成分黄芪甲甙对病毒性心肌炎(VM)小鼠心肌中神经生长因子(NGF)表达的影响。方法Balb/c小鼠100只,随机分成6组。非感染小鼠腹腔无菌注射病毒培养液,分为正常对照组[A组,10只,以羧甲基纤维素钠(CMC)0.1 mL灌胃7 d]、高剂量对照组(B组,10只,9%黄芪甲甙液0.1 mL灌胃7 d);余80只小鼠以柯萨奇病毒(CVB3)腹腔无菌注射制作VM模型,VM小鼠随机分为心肌炎对照组和低、中、高剂量干预组,分别以CMC、1%、3%、9%黄芪甲甙液0.1 mL灌胃7 d(分别为C、D、E、F组,每组20只)。14 d后处死小鼠并取其心脏,采用RT-PCR和免疫组织化学检测NGF mRNA及蛋白表达水平。结果F组小鼠较C组死亡率明显降低,B组无小鼠死亡;与C组比较,NGF mRNA、蛋白表达水平以及心肌病变积分在F组均显著下降,而低、中剂量黄芪甲甙对心肌炎小鼠NGF mRNA、蛋白表达及心肌病变积分无明显影响。结论黄芪甲甙可能通过抑制NGF表达,对Balb/c小鼠CVB3心肌炎具有良好的治疗作用。     

黄芪甲甙对病毒性心肌炎小鼠心肌柯萨奇病毒受体基因表达的影响

目的　探讨黄芪活性成分黄芪甲甙对病毒性心肌炎 (VM)小鼠心肌柯萨奇 腺病毒受体 (CAR)基因表达影响。方法　Balb/c小鼠 1 0 0只 ,分为 6组。非感染小鼠腹腔无菌注射病毒培养液 ,分为正常对照组 (A组 ,1 0只 ,以羧甲基纤维素钠 0 .1mL灌胃 7d)、9%黄芪甲甙对照组 (B组 ,1 0只 ,9%黄芪甲甙 0 .1mL灌胃 7d) ;余 80只小鼠以柯萨奇病毒 (CVB3)腹腔无菌注射制作病毒性心肌炎模型 ,VM小鼠随机分为心肌炎对照组和 1 %、3 %、9%黄芪甲甙干预心肌炎组 ,分别以生理盐水、1 %、3 %、9%黄芪甲甙 0 .1mL灌胃 7d(分别为C、D、E、F组 ,每组 2 0只 )。 1 4d后处死一小部分鼠并取其心脏。采用RT PCR检测心肌CARmRNA表达水平。结果　F组小鼠死亡率较C组明显降低 (1 0 %与 45 %比较 ) ,(χ2 =6 .1 4　P <0 .0 5) ,B组无小鼠死亡 ;与C组相比较 ,CARmRNA表达水平以心肌病变积分在F组显著下降 ,而 1 %、3 %黄芪甲甙对心肌炎小鼠CARmRNA表达及心肌病变积分无明显影响。结论　 9%黄芪甲甙可抑制CAR表达 ,提高心肌炎小鼠生存率 ,减轻心肌损害 ,安全有效 ,对VM有良好的治疗作用。     

黄芪甲甙对病毒性心肌炎小鼠心肌组织蛋白酶L表达的作用

目的探讨黄芪活性成分黄芪甲甙对病毒性心肌炎(VMC)小鼠心肌中组织蛋白酶L(cathepsinL,CL)表达的作用。方法BALB/C小鼠100只,随机分成6组。非感染小鼠腹腔无菌注射病毒培养液,分为正常对照组(A组10只,以羧甲基纤维素钠0.1ml灌胃7d)、9%黄芪甲甙对照组(B组10只,9%黄芪甲甙0.1ml灌胃7d);余80只小鼠以柯萨奇病毒(CVB3)腹腔无菌注射制作VMC模型,VMC小鼠随机分为心肌炎对照组和1%、3%、9%黄芪甲甙干预心肌炎组,分别以羧甲基纤维素钠及1%、3%、9%黄芪甲甙0.1ml灌胃7d(分别为C、D、E、F组,每组20只)。14d后处死全部小鼠并取其心脏。采用RT_PCR和免疫组化半定量检测心肌CLmRNA及蛋白表达水平。结果F组小鼠较C组死亡率明显降低[10%(2/20例)vs45%(9/20例),χ2=6.14,P<0.05],B组无小鼠死亡;与C组相比,CLmRNA、蛋白表达水平以及心肌病变积分在F组均显著下降,而1%、3%黄芪甲甙对心肌炎小鼠CLmRNA、蛋白表达及心肌病变积分无明显影响。结论黄芪甲甙可能通过抑制cathepsinL表达,对BALB/C小鼠CVB3心肌炎具有良好的治疗作用。     

黄芪甲甙对急性病毒性心肌炎小鼠IGF-1及相关蛋白表达的作用研究

目的：探讨黄芪甲甙在治疗病毒性心肌炎过程中对胰岛素样生长因子-1（IGF-1）及相关蛋白的影响。方法：65只4周龄Balb/C小鼠随机分为正常对照、黄芪对照、病毒对照及黄芪小剂量、黄芪大剂量等5组。后3组腹腔接种柯萨基B组病毒（CVB3）病毒。黄芪小剂量、黄芪大剂量每日分别给予0.07、0.6 mg/kg黄芪甲甙液灌胃1次。15 d后采血、取心肌组织,用酶标免疫吸附测定法(ELISA)测血浆中IGF-1的表达,用免疫组织化学法检测心肌组织中IGF-1及相关蛋白的蛋白表达,用逆转录聚合酶链反应（RT-PCR）法检测心肌组织IGF-1基因表达。结果：感染CVB3病毒后小鼠心肌组织IGF-1及相关蛋白明显升高,大剂量黄芪甲甙干预可调节小鼠IGF-1及相关蛋白的表达;小剂量黄芪甲甙则无明显效果。结论：大剂量黄芪甲甙对急性病毒性心肌炎小鼠心肌组织的保护作用可能是通过影响IGF-1及相关蛋白表达的途径来实现。     

纳米α-亚麻酸对病毒性心肌炎小鼠巨噬细胞移动抑制因子表达的影响

目的 探讨纳米α-亚麻酸对病毒性心肌炎(VM)小鼠巨噬细胞移动抑制因子(MIF)表达的影响.方法 80只雄性Balb/c小鼠随机分为对照组、模型组、低剂量干预组及高剂量干预组,每组20只.对照组小鼠腹腔接种病毒培养液,余3组经腹腔接种柯萨奇病毒(CVB3)诱发VM,低、高剂量干预组于病毒接种当天分别以60、180 ms/kg纳米α-亚麻酸0.1 mL灌胃,对照组和模型组均以9 s/L盐水0.1 mL灌胃,1次/d,连续7 d,第15天处死全部存活小鼠,采用RT-PCR和免疫组织化学法检测其心肌MIF mRNA及蛋白表达,采用ELISA法测定其血清MIF水平.行HE染色检查心肌病理变化.结果 对照组、模型组、低剂量干预组、高剂量干预组小鼠死亡率分别为0、45%、30%、20%,高剂量干预组死亡率显著低于模型组(P<0.05),低剂量干预组和模型组比较无显著性差异(P>0.05);模型组心肌MIF mRNA和蛋白表达水平、血清MIF水平均显著高于对照组(Pa<0.01),而低、高剂量干预组MIFmRNA和蛋白表达水平、血清MIF水平、心肌病理积分均较模型组显著降低(Pa<0.05).结论 纳米α-亚麻酸可通过抑制MIF表达减轻VM小鼠心肌损害,提高VM小鼠生存率.     

基质金属蛋白酶-3在病毒性心肌炎中的表达及福辛普利的干预作用

目的探讨基质金属蛋白酶-3(MMP-3)在病毒性心肌炎(VM)小鼠中的表达及福辛普利的干预作用。方法鼠龄4~6周Balb/c纯种雄性小鼠57只随机分为对照组(A组)、模型组(B组)、假干预组(C组)、福辛普利组(D组)。B~D组小鼠腹腔接种0.1mL柯萨奇病毒B3(CVB3)建立VM模型。C、D组于注射CVB324h后分别予生理盐水、福辛普利灌胃治疗,d14断颈处死小鼠,心脏石蜡切片HE染色计算病理积分,免疫组化法检测心肌Ⅰ、Ⅲ型胶原蛋白表达,逆转录-聚合酶链反应(RT-PCR)检测MMP-3mRNA表达。结果B、C组心肌MMP-3表达显著上调,心肌Ⅰ、Ⅲ型胶原增生显著与A组比较(P<0.05);D组心肌MMP-3表达显著下调,与B组比较心肌Ⅰ、Ⅲ型胶原增生显著减少(P<0.05)。结论MMP-3参与VM小鼠病理过程,福辛普利能明显下调MMP-3mRNA表达,显著减少心肌胶原增生。     

单核细胞趋化蛋白-1在病毒性心肌炎小鼠心肌中表达及意义

目的探讨单核细胞趋化蛋白-1(MCP-1)在实验性小鼠病毒性心肌炎(VM)发病中的作用。方法 80只小鼠随机分为2组,VM组(n=70)腹腔接种0.1 ml柯萨基病毒B3(CVB3)建立VM动物模型;对照组(n=10)腹腔接种0.1 ml Eagle's液。VM组于接种后3、7、15、30 d处死,对照组于30 d处死,采用RT-PCR、免疫组织化学染色检测心肌MCP-1 mRNA及蛋白表达,HE染色检查心肌病理变化,并对MCP-1蛋白表达与心肌病变积分进行相关性分析。结果 VM组各时点心肌MCP-1 mRNA及蛋白表达均显著高于对照组(P0.05或0.01),MCP蛋白表达与心肌病变积分呈正相关(r=0.76,P0.05)。结论 MCP-1过度表达可能在VM发病机制中起重要作用。     

栀子等中药治疗小鼠病毒性心肌炎实验研究

目的观察栀子等中药抗Balb/c小鼠Coxsakie B3病毒(CVB3)感染的急性病毒性心肌炎的疗效。方法将Balb/c小鼠随机分为模型组、栀子组、黄连组、黄芩组、大青叶组、复方组及正常对照组,腹腔注射CVB3建立病毒性心肌炎模型,用上述中药进行灌胃治疗7 d,检测小鼠心脏CVB3,病毒滴定、心肌病变形态定量分析及电镜观察细胞超微结构改变。结果中药治疗各组病毒滴定、心肌病变面积及细胞超微结构改变均较模型组减轻,复方组最轻。结论上述中药对小鼠病毒性心肌炎有一定治疗作用。     

利巴韦林对病毒性心肌炎的疗效及机制的实验研究

目的研究利巴韦林对小鼠病毒性心肌炎(VM)的疗效及机制。方法将Balb/c小鼠120只随机分为A组:空白对照组、B组:病毒对照组、C组:利巴韦林治疗组,B、C组接种0.2mL(10-7.5Tcid50/mL)柯萨奇B3(CVB3)病毒液,接种后d7、14、21、28分别处死10只,观察小鼠病死率、心肌光镜和电镜检查病理变化,计算心肌病理积分,检测心肌病毒滴度、血清肌钙蛋白I(cTnI)、血清丙二醛(MDA)、心肌细胞凋亡率(CMAR)。结果治疗组小鼠病死率、心肌病毒滴度、心肌病理积分、血清cTnI显著低于病毒对照组,血清MDA、CMAR无显著性差异。结论利巴韦林对小鼠VM有较好疗效,其机制主要是降低心肌病毒滴度,从而降低血清cTnI,减轻心肌病变。     

病毒性心肌炎不同时点血管内皮细胞生长因子mRNA的表达

目的 探讨血管内皮细胞生长因子(VEGF)在BALB/c小鼠感染柯萨奇病毒B3(CVB3)所致病毒性心肌炎(VM)病程中的作用.方法 取BALB/c小鼠70只,随机分为VM组60只,腹腔感染CVB3,分别于实验第3、7、10、14、18、21天取心肌组织;正常组10只,于实验第21天取心肌组织.用逆转录聚合酶链反应(RT-PCR)技术检测其心肌组织VEGF mRNA的表达.结果 病毒性心肌炎小鼠心肌VEGF mRNA表达较正常组高,且在感染病毒后表达渐增高,14 d达最高峰,其后表达降低,但仍维持一较高水平,与正常组比较仍有统计学意义(P<0.01).VEGF mRNA表达与心肌病理损害程度密切相关.结论 VEGF可能参与BALB/c小鼠病毒性心肌炎的病理生理过程.     

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.